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Sample records for anticancer transcript-level effects

  1. 1,25 dihydroxyvitamin D-mediated orchestration of anticancer, transcript-level effects in the immortalized, non-transformed prostate epithelial cell line, RWPE1

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    Clinton Steve K

    2010-01-01

    Full Text Available Abstract Background Prostate cancer is the second leading cause of cancer mortality among US men. Epidemiological evidence suggests that high vitamin D status protects men from prostate cancer and the active form of vitamin D, 1α,25 dihydroxyvitamin D3 (1,25(OH2D has anti-cancer effects in cultured prostate cells. Still, the molecular mechanisms and the gene targets for vitamin D-mediated prostate cancer prevention are unknown. Results We examined the effect of 1,25(OH2D (+/- 100 nM, 6, 24, 48 h on the transcript profile of proliferating RWPE1 cells, an immortalized, non-tumorigenic prostate epithelial cell line that is growth arrested by 1,25(OH2D (Affymetrix U133 Plus 2.0, n = 4/treatment per time and dose. Our analysis revealed many transcript level changes at a 5% false detection rate: 6 h, 1571 (61% up, 24 h, 1816 (60% up, 48 h, 3566 (38% up. 288 transcripts were regulated similarly at all time points (182 up, 80 down and many of the promoters for these transcripts contained putative vitamin D response elements. Functional analysis by pathway or Gene Set Analysis revealed early suppression of WNT, Notch, NF-kB, and IGF1 signaling. Transcripts related to inflammation were suppressed at 6 h (e.g. IL-1 pathway and suppression of proinflammatory pathways continued at later time points (e.g. IL-17 and IL-6 pathways. There was also evidence for induction of anti-angiogenic pathways and induction of transcripts for protection from oxidative stress or maintenance of cell redox homeostasis at 6 h. Conclusions Our data reveal of large number of potential new, direct vitamin D target genes relevant to prostate cancer prevention. In addition, our data suggests that rather than having a single strong regulatory effect, vitamin D orchestrates a pattern of changes within prostate epithelial cells that limit or slow carcinogenesis.

  2. Effect of irradiation on POMC transcription level in peritoneal macrophages of mice

    International Nuclear Information System (INIS)

    Objective: To investigate the effect of irradiation (75 mGy, 2.0 Gy) on the mRNA transcriptional level of POMC in peritoneal macrophages of mice. Methods: In situ hybridization (ISH) was used to examine the changes of POMC mRNA transcription level. Results: the positive cells were stained in blue-purple color. The POMC mRNA transcription was increased from 2 h to 8 h after WBI with 0.075 Gy, returning to the control level at 16 h. No detectable POMC mRNA transcription was found at different time points after WBI with 2 gy. Conclusion: Low dose irradiation could increase transcription level of POMC in peritoneal MΦ; whereas, high dose radiation could inhibit the POMC mRNA transcription level

  3. Effect of low dose radiation on POMC transcription level in mouse hypothalamus and immune organs

    International Nuclear Information System (INIS)

    Objective: To disclose the changes in mRNA transcription level of POMC in the hypothalamus and immune organs after low dose radiation. Method: In situ hybridization was used to examine the changes of POMC mRNA transcription level in mouse hypothalamus and immune organs following whole body irradiation (WBI) with 75 mGy X-rays. Results: There was a basal expression of POMC mRNA in both the hypothalamus and immune organs. POMC mRNA-positive neutron were located in the arcuate nucleus of hypothalamus. WBI with 75 mGy X-rays could significantly down-regulate the POMC transcription level that was remarkable within 1h and remained low in the observation period of 12h. POMC transcription level in mouse immune organs increased with time within 8h after irradiation and then began to decrease but still remained at a higher than normal level. The changes of POMC transcription level were more marked in the spleen than in other immune organs. Conclusion: These findings suggest that the immediate decrease of POMC transcription level in the hypothalamus might be the direct cause of the down-regulation of the hypothalamus-pituitary-adrenocortical axis after WBI with 75 mGy X-rays, accompanied with an increase in POMC transcription in immune organs

  4. Melatonin Anticancer Effects: Review

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    Luigi Di Bella

    2013-01-01

    Full Text Available Melatonin (N-acetyl-5-methoxytryptamine, MLT, the main hormone produced by the pineal gland, not only regulates circadian rhythm, but also has antioxidant, anti-ageing and immunomodulatory properties. MLT plays an important role in blood composition, medullary dynamics, platelet genesis, vessel endothelia, and in platelet aggregation, leukocyte formula regulation and hemoglobin synthesis. Its significant atoxic, apoptotic, oncostatic, angiogenetic, differentiating and antiproliferative properties against all solid and liquid tumors have also been documented. Thanks, in fact, to its considerable functional versatility, MLT can exert both direct and indirect anticancer effects in factorial synergy with other differentiating, antiproliferative, immunomodulating and trophic molecules that form part of the anticancer treatment formulated by Luigi Di Bella (Di Bella Method, DBM: somatostatin, retinoids, ascorbic acid, vitamin D3, prolactin inhibitors, chondroitin-sulfate. The interaction between MLT and the DBM molecules counters the multiple processes that characterize the neoplastic phenotype (induction, promotion, progression and/or dissemination, tumoral mutation. All these particular characteristics suggest the use of MLT in oncological diseases.

  5. Effect of exogenous hormones on transcription levels of pyridoxal 5'-phosphate biosynthetic enzymes in the silkworm (Bombyx mori).

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    Huang, ShuoHao; Yang, HuanHuan; Yao, LiLi; Zhang, JianYun; Huang, LongQuan

    2016-01-01

    Vitamin B6 includes 6 pyridine derivatives, among which pyridoxal 5'-phosphate is a coenzyme for over 140 enzymes. Animals acquire their vitamin B6 from food. Through a salvage pathway, pyridoxal 5'-phosphate is synthesized from pyridoxal, pyridoxine or pyridoxamine, in a series of reactions catalyzed by pyridoxal kinase and pyridoxine 5'-phosphate oxidase. The regulation of pyridoxal 5'-phospahte biosynthesis and pyridoxal 5'-phospahte homeostasis are at the center of study for vitamin B6 nutrition. How pyridoxal 5'-phosphate biosynthesis is regulated by hormones has not been reported so far. Our previous studies have shown that pyridoxal 5'-phosphate level in silkworm larva displays cyclic developmental changes. In the current study, effects of exogenous juvenile hormone and molting hormone on the transcription level of genes coding for the enzymes involved in the biosynthesis of pyridoxal 5'-phospahte were examined. Results show that pyridoxal kinase and pyridoxine 5'-phosphate oxidase are regulated at the transcription level by development and are responsive to hormones. Molting hormone stimulates the expression of genes coding for pyridoxal kinase and pyridoxine 5'-phosphate oxidase, and juvenile hormone appears to work against molting hormone. Whether pyridoxal 5'-phosphate biosynthesis is regulated by hormones in general is an important issue for further studies. PMID:26780217

  6. Ganoderma: insights into anticancer effects.

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    Kladar, Nebojša V; Gavarić, Neda S; Božin, Biljana N

    2016-09-01

    The genus Ganoderma includes about 80 species growing on cut or rotten trees. The most commonly used species is Ganoderma ludicum. Biomolecules responsible for the health benefits of Ganoderma are polysaccharides with an immunostimulative effect and triterpenes with a cytotoxic action. For more than 2000 years, it has been used traditionally in the treatment of various pathological conditions and recently, its immunoregulatory, antiviral, antibacterial, antioxidant, hepatoprotective, and anticancer potential has been confirmed. A wide range of Ganoderma extracts and preparations arrest the cell cycle in different phases and consequently inhibit the growth of various types of cancer cells. Extracts containing polysaccharides stimulate immunological reactions through the production of various cytokines and mobilization of immune system cells. In-vivo studies have confirmed the anticancer potential and the antimetastatic effects of compounds originating from Ganoderma. There is also evidence for the chemopreventive action of Ganoderma extracts in bladder, prostate, liver, and breast cancer. The results of clinical studies suggest the combined use of G. lucidum with conventional chemotherapy/radiotherapy, but the methodology and the results of these studies are being questioned. Therefore, a constant need for new clinical trials exists. PMID:26317382

  7. B-chromosome effects on Hsp70 gene expression does not occur at transcriptional level in the grasshopper Eyprepocnemis plorans.

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    Navarro-Domínguez, Beatriz; Cabrero, Josefa; Camacho, Juan Pedro M; López-León, María Dolores

    2016-10-01

    As intragenomic parasites, B chromosomes can elicit stress in the host genome, thus inducing a response for host adaptation to this kind of continuous parasitism. In the grasshopper Eyprepocnemis plorans, B-chromosome presence has been previously associated with a decrease in the amount of the heat-shock protein 70 (HSP70). To investigate whether this effect is already apparent at transcriptional level, we analyze the expression levels of the Hsp70 gene in gonads and somatic tissues of males and females with and without B chromosomes from two populations, where the predominant B chromosome variants (B2 and B24) exhibit different levels of parasitism, by means of quantitative real-time PCR (qPCR) on complementary DNA (cDNA). The results revealed the absence of significant differences for Hsp70 transcripts associated with B-chromosome presence in virtually all samples. This indicates that the decrease in HSP70 protein levels, formerly reported in this species, may not be a consequence of transcriptional down-regulation of Hsp70 genes, but the result of post-transcriptional regulation. These results will help to design future studies oriented to identifying factors modulating Hsp70 expression, and will also contribute to uncover the biological role of B chromosomes in eukaryotic genomes. PMID:27334602

  8. Modeling RNA polymerase competition: the effect of σ-subunit knockout and heat shock on gene transcription level

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    Seliverstov Alexandr V

    2011-01-01

    Full Text Available Abstract Background Modeling of a complex biological process can explain the results of experimental studies and help predict its characteristics. Among such processes is transcription in the presence of competing RNA polymerases. This process involves RNA polymerases collision followed by transcription termination. Results A mathematical and computer simulation model is developed to describe the competition of RNA polymerases during genes transcription on complementary DNA strands. E.g., in the barley Hordeum vulgare the polymerase competition occurs in the locus containing plastome genes psbA, rpl23, rpl2 and four bacterial type promoters. In heat shock experiments on isolated chloroplasts, a twofold decrease of psbA transcripts and even larger increase of rpl23-rpl2 transcripts were observed, which is well reproduced in the model. The model predictions are in good agreement with virtually all relevant experimental data (knockout, heat shock, chromatogram data, etc.. The model allows to hypothesize a mechanism of cell response to knockout and heat shock, as well as a mechanism of gene expression regulation in presence of RNA polymerase competition. The model is implemented for multiprocessor platforms with MPI and supported on Linux and MS Windows. The source code written in C++ is available under the GNU General Public License from the laboratory website. A user-friendly GUI version is also provided at http://lab6.iitp.ru/en/rivals. Conclusions The developed model is in good agreement with virtually all relevant experimental data. The model can be applied to estimate intensities of binding of the holoenzyme and phage type RNA polymerase to their promoters using data on gene transcription levels, as well as to predict characteristics of RNA polymerases and the transcription process that are difficult to measure directly, e.g., the intensity (frequency of holoenzyme binding to the promoter in correlation to its nucleotide composition and the

  9. Autogenous regulation of the EcoRII methylase gene at the transcriptional level: effect of 5-azacytidine.

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    Som, S; Friedman, S

    1993-01-01

    mRNA of the EcoRII methylase (M.EcoRII), a type II modification enzyme, was induced when Escherichia coli carrying a cloned M.EcoRII gene was exposed to the bacteriocidal drug 5-azacytidine. Induction occurred only when transcription was initiated from its own promoter. When the 5' promoter sequences were deleted or replaced with the lac promoter sequences, no induction occurred. The induction was independent of the template DNA level, but the presence of an intact M.EcoRII protein was a requirement. The drug is incorporated into DNA which then inhibits M.EcoRII by binding tightly to the enzyme. A deletion within the M.EcoRII coding region caused a marked increase in the basal level of mRNA transcribed from the M.EcoRII promoter, but no induction occurred upon 5-azacytidine treatment. The level could be reduced to normal by M.EcoRII in trans. In vitro, the enzyme bound to the sequences upstream of the transcription start sites and inhibited the initiation of transcription. These experiments indicate that expression of the M.EcoRII gene was autogenously regulated at the transcriptional level. Similar regulation is also noted in another DNA (cytosine-5) methylase, M.MspI. Images PMID:7693455

  10. A Systematic Review of Iran's Medicinal Plants With Anticancer Effects.

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    Asadi-Samani, Majid; Kooti, Wesam; Aslani, Elahe; Shirzad, Hedayatollah

    2016-04-01

    Increase in cases of various cancers has encouraged the researchers to discover novel, more effective drugs from plant sources. This study is a review of medicinal plants in Iran with already investigated anticancer effects on various cell lines. Thirty-six medicinal plants alongside their products with anticancer effects as well as the most important plant compounds responsible for the plants' anticancer effect were introduced. Phenolic and alkaloid compounds were demonstrated to have anticancer effects on various cancers in most studies. The plants and their active compounds exerted anticancer effects by removing free radicals and antioxidant effects, cell cycle arrest, induction of apoptosis, and inhibition of angiogenesis. The investigated plants in Iran contain the compounds that are able to contribute effectively to fighting cancer cells. Therefore, the extract and active compounds of the medicinal plants introduced in this review article could open a way to conduct clinical trials on cancer and greatly help researchers and pharmacists develop new anticancer drugs. PMID:26297173

  11. In vivo evaluation on the effects of HemoHIM in promoting anticancer activities and reducing the side-effects of anticancer drugs

    International Nuclear Information System (INIS)

    In this project, we aimed to obtain the preclinical in vivo evaluation data for the development of the herbal composition (HemoHIM) as the auxiliary agent for the anticancer treatment that can reduce the side-effects of anticancer drugs and enhance their anticancer activities. Firstly, in vitro studies showed that HemoHIM did not show any effects on the tumor cell growth inhibition by 2 anticancer drugs (cisplatin, 5-FU), which indicated that at least HemoHIM does not exert any adverse effects on the activities of anticancer drugs. Next, the in vivo studies with mice implanted with tumor cells(B16F0, LLC1) showed that HemoHIM partially enhanced the anticancer activities of drugs (cisplatin, 5-FU), and improved endogenous anticancer immune activities. Furthermore, in the same animal models, HemoHIM effectively reduced the side-effects of anticancer drugs (liver and renal toxicities by cisplatin, immune and hematopoietic disorders by 5-FU). These results collectively showed that HemoHIM can enhance the activities of anticancer drugs and reduce their side-effects in vitro and in vivo and HemoHIM does not exert any adverse effects on the efficacy of anticancer drugs. The results of this project can be utilized as the basic preclinical data for the development and approval of HemoHIM as the auxiliary agent for the anticancer treatment

  12. In vivo evaluation on the effects of HemoHIM in promoting anticancer activities and reducing the side-effects of anticancer drugs

    Energy Technology Data Exchange (ETDEWEB)

    Jo, Sung Kee; Jung, U Hee; Park, Hae Ran; Ju, Eun Jin; Cho, Eun Hee

    2009-07-15

    In this project, we aimed to obtain the preclinical in vivo evaluation data for the development of the herbal composition (HemoHIM) as the auxiliary agent for the anticancer treatment that can reduce the side-effects of anticancer drugs and enhance their anticancer activities. Firstly, in vitro studies showed that HemoHIM did not show any effects on the tumor cell growth inhibition by 2 anticancer drugs (cisplatin, 5-FU), which indicated that at least HemoHIM does not exert any adverse effects on the activities of anticancer drugs. Next, the in vivo studies with mice implanted with tumor cells(B16F0, LLC1) showed that HemoHIM partially enhanced the anticancer activities of drugs (cisplatin, 5-FU), and improved endogenous anticancer immune activities. Furthermore, in the same animal models, HemoHIM effectively reduced the side-effects of anticancer drugs (liver and renal toxicities by cisplatin, immune and hematopoietic disorders by 5-FU). These results collectively showed that HemoHIM can enhance the activities of anticancer drugs and reduce their side-effects in vitro and in vivo and HemoHIM does not exert any adverse effects on the efficacy of anticancer drugs. The results of this project can be utilized as the basic preclinical data for the development and approval of HemoHIM as the auxiliary agent for the anticancer treatment

  13. Effects of the lipid regulating drug clofibric acid on PPARα-regulated gene transcript levels in common carp (Cyprinus carpio) at pharmacological and environmental exposure levels

    Energy Technology Data Exchange (ETDEWEB)

    Corcoran, Jenna, E-mail: J.F.Corcoran@exeter.ac.uk [University of Exeter, Biosciences, College of Life & Environmental Sciences, Exeter EX4 4QD (United Kingdom); Winter, Matthew J., E-mail: M.Winter@exeter.ac.uk [AstraZeneca Global Environment, Brixham Laboratory, Freshwater Quarry, Brixham TQ5 8BA (United Kingdom); Lange, Anke, E-mail: A.Lange@exeter.ac.uk [University of Exeter, Biosciences, College of Life & Environmental Sciences, Exeter EX4 4QD (United Kingdom); Cumming, Rob, E-mail: Rob.Cumming@astrazeneca.com [AstraZeneca Global Environment, Brixham Laboratory, Freshwater Quarry, Brixham TQ5 8BA (United Kingdom); Owen, Stewart F., E-mail: Stewart.Owen@astrazeneca.com [AstraZeneca Global Environment, Brixham Laboratory, Freshwater Quarry, Brixham TQ5 8BA (United Kingdom); Tyler, Charles R., E-mail: C.R.Tyler@exeter.ac.uk [University of Exeter, Biosciences, College of Life & Environmental Sciences, Exeter EX4 4QD (United Kingdom)

    2015-04-15

    Highlights: • CFA appears to have a low propensity to bioconcentrate and has a plasma half-life of <4 days in carp. • CFA increases levels of mRNA of a number of genes known to be regulated by PPARα in mammals. • PPARα activation changes levels of mRNA of genes involved with several detoxification/ biotransformation system components in carp. • CFA alters levels of mRNA and activity of the inducible β-oxidation pathway enzyme Acox1, a known indicator of peroxisome proliferator exposure. - Abstract: In mammals, the peroxisome proliferator-activated receptor α (PPARα) plays a key role in regulating various genes involved in lipid metabolism, bile acid synthesis and cholesterol homeostasis, and is activated by a diverse group of compounds collectively termed peroxisome proliferators (PPs). Specific PPs have been detected in the aquatic environment; however little is known on their pharmacological activity in fish. We investigated the bioavailability and persistence of the human PPARα ligand clofibric acid (CFA) in carp, together with various relevant endpoints, at a concentration similar to therapeutic levels in humans (20 mg/L) and for an environmentally relevant concentration (4 μg/L). Exposure to pharmacologically-relevant concentrations of CFA resulted in increased transcript levels of a number of known PPARα target genes together with increased acyl-coA oxidase (Acox1) activity, supporting stimulation of lipid metabolism pathways in carp which are known to be similarly activated in mammals. Although Cu,Zn-superoxide dismutase (Sod1) activity was not affected, mRNA levels of several biotransformation genes were also increased, paralleling previous reports in mammals and indicating a potential role in hepatic detoxification for PPARα in carp. Importantly, transcription of some of these genes (and Acox1 activity) were affected at exposure concentrations comparable with those reported in effluent discharges. Collectively, these data suggest that CFA

  14. Effects of the lipid regulating drug clofibric acid on PPARα-regulated gene transcript levels in common carp (Cyprinus carpio) at pharmacological and environmental exposure levels

    International Nuclear Information System (INIS)

    Highlights: • CFA appears to have a low propensity to bioconcentrate and has a plasma half-life of <4 days in carp. • CFA increases levels of mRNA of a number of genes known to be regulated by PPARα in mammals. • PPARα activation changes levels of mRNA of genes involved with several detoxification/ biotransformation system components in carp. • CFA alters levels of mRNA and activity of the inducible β-oxidation pathway enzyme Acox1, a known indicator of peroxisome proliferator exposure. - Abstract: In mammals, the peroxisome proliferator-activated receptor α (PPARα) plays a key role in regulating various genes involved in lipid metabolism, bile acid synthesis and cholesterol homeostasis, and is activated by a diverse group of compounds collectively termed peroxisome proliferators (PPs). Specific PPs have been detected in the aquatic environment; however little is known on their pharmacological activity in fish. We investigated the bioavailability and persistence of the human PPARα ligand clofibric acid (CFA) in carp, together with various relevant endpoints, at a concentration similar to therapeutic levels in humans (20 mg/L) and for an environmentally relevant concentration (4 μg/L). Exposure to pharmacologically-relevant concentrations of CFA resulted in increased transcript levels of a number of known PPARα target genes together with increased acyl-coA oxidase (Acox1) activity, supporting stimulation of lipid metabolism pathways in carp which are known to be similarly activated in mammals. Although Cu,Zn-superoxide dismutase (Sod1) activity was not affected, mRNA levels of several biotransformation genes were also increased, paralleling previous reports in mammals and indicating a potential role in hepatic detoxification for PPARα in carp. Importantly, transcription of some of these genes (and Acox1 activity) were affected at exposure concentrations comparable with those reported in effluent discharges. Collectively, these data suggest that CFA

  15. Anticancer Activity of Chamaejasmine: Effect on Tubulin Protein

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    Yingkun Nie

    2011-07-01

    Full Text Available In this work, the anticancer activity of chamaejasmine was studied by evaluating its in vitro cytotoxicity against several human cancer cell lines (MCF-7, A549, SGC-7901, HCT-8, HO-4980, Hela, HepG2, PC-3, LNCap, Vero and MDCK using the MTT assay. Results indicated chamaejasmine showed more notable anticancer activity than taxol against PC-3 cells, with IC50 values of 2.28 and 3.98 µM, respectively. Furthermore, Western blot analysis showed that chamaejasmine was able to increase the expression of β-tubulin, but not α-tubulin. In silico simulations indicated that chamaejasmine specifically interacts with the active site which is located at the top of β-tubulin, thanks to the presence of strong hydrophobic effects between the core templates and the hydrophobic surface of the TB active site. The binding energy (Einter was calculated to be −164.77 kcal·mol−1. Results presented here suggest that chamaejasmine possesses anti-cancer properties relating to β-tubulin depolymerization inhibition, and therefore is a potential source of anticancer leads for the pharmaceutical industry.

  16. Anticancer Effects of HESA-A:An Herbal Marine Compound

    Institute of Scientific and Technical Information of China (English)

    Amrollah Ahmadi; Gholamreza Habibi; Mehdi Farrokhnia

    2010-01-01

    @@ HESA-A,a natural biological compound,is a mixture of herbal-marine substances that includes Penaeus latisculatus (king prawn),Carum carvi and Apium graveolens with anticancer properties(1,2).Although the exact mechanism of action of HESA-A on tumor cells is not fully understood,it appears to have multiple pharmacological effects(2). The lack of selectivity for tumor cells,which is associated with conventional cancer chemotherapy,is the main cause of chemotherapy complications and failure of anticancer agents.Many complementary and alternative medicine (CAM) studies are focused on products obtained from plants,animals or other natural sources to find compounds with high therapeutic indices.HESA-A inhibits the growth of cancer cells selectively and in a dose dependent manner.At the highest concentration (5.4 mg/mL),HESA-A completely inhibits the growth of cells and this effect gradually decreases as the dose is reduced.HESA-A is not cytotoxic towards normal cell lines unlike cancer cells.A major concern in this selectivity effect is the possible interaction with the cell DNA.The apoptotic effects of HESA-A may also have a major role in its anticancer properties(3,4).

  17. Antimutagenicity and Anticancer Effects of Citrus Medica Fruit Juice

    OpenAIRE

    Majd Ahmad; Falahian Fathollah; Mehrabian Sedigheh; Hashemi Mehrdad; Ardeshiry Lajimi Abdolreza; Entezari Maliheh

    2009-01-01

    Currently cancer is considered as one of the main factors of mortality globally. Many chemicals in our environment can cause genetic mutations and are potentially responsible for millions of cancer-related deaths. Nowadays the scientists are looking for food materials which can potenthially prevent the cancer occurrence. The purpose of this research is to examine antimutagenicity and anticancer effect of Citrus Medica fruit juice.In present study human astrocytoma cancer cells were cultured i...

  18. Antimutagenicity and Anticancer Effects of Citrus Medica Fruit Juice

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    Majd Ahmad

    2009-10-01

    Full Text Available Currently cancer is considered as one of the main factors of mortality globally. Many chemicals in our environment can cause genetic mutations and are potentially responsible for millions of cancer-related deaths. Nowadays the scientists are looking for food materials which can potenthially prevent the cancer occurrence. The purpose of this research is to examine antimutagenicity and anticancer effect of Citrus Medica fruit juice.In present study human astrocytoma cancer cells were cultured in DMEM (Gibco,supplemented with 10% fetal calf serum,peniciline-streptomycin,L-glutamine and incubated at 37 ºC for 2 days.In addition cancer cell line were treated by half-ripe and ripe Citrus Medica fruit juice and cellular vital capacity was determined by MTT. The Citrus Medica fruit juice was subsequenthy evaluated in terms of antimutagenicity and anticancer properties by a standard reverse mutation assay (Ames Test. This was performed with histidine auxotroph strain of Salmonella typhimurium (TA100 .Thus, it requires histidine from a foreign supply to ensure its growth.The aforementioned strain gives rise to reverted colonies when expose to carcinogen substance (Sodium Azide. During MTT, human astrocytoma cell line revealed to have a meaningful cell death when compared with controls (P<0.01. In Ames Test the fruit juice prevented the reverted mutations and the hindrance percent of half-ripe Citrus Medica was 71.7% and ripe Citrus Medica was 34.4% in antimutagenicity test and this value in anticancer test was 83.3% and 50% in half-ripe Citrus Medica and ripe Citrus Medica respectively.This is the first study that have revealed antimutagenicity and anticancer effect of Citrus Medica fruit juice and the effects were higher in half-ripe Citrus Medica in comparison to the riprned one.

  19. Mechanistic Insights of Vitamin D Anticancer Effects.

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    Ma, Yingyu; Johnson, Candace S; Trump, Donald L

    2016-01-01

    Vitamin D is a secosteroid hormone that regulates many biological functions in addition to its classical role in maintaining calcium homeostasis and bone metabolism. Vitamin D deficiency appears to predispose individuals to increased risk of developing a number of cancers. Compelling epidemiological and experimental evidence supports a role for vitamin D in cancer prevention and treatment in many types of cancers. Preclinical studies show that 1,25D3, the active metabolite of vitamin D, and its analogs have antitumor effects in vitro and in vivo through multiple mechanisms including the induction of cell cycle arrest, apoptosis, differentiation and the suppression of inflammation, angiogenesis, invasion, and metastasis. 1,25D3 also potentiates the effect of chemotherapeutic agents and other agents in the combination treatment. In this review, the antitumor effects of 1,25D3 and the potential underlying mechanisms will be discussed. The current findings support the application of 1,25D3 in cancer prevention and treatment. PMID:26827961

  20. Pharmacokinetic characteristics and anticancer effects of 5-Fluorouracil loaded nanoparticles

    International Nuclear Information System (INIS)

    It is expected that prolonged circulation of anticancer drugs will increase their anticancer activity while decreasing their toxic side effects. The purpose of this study was to prepare 5-fluorouracil (5-FU) loaded block copolymers, with poly(γ-benzyl-L-glutamate) (PBLG) as the hydrophobic block and poly(ethylene glycol) (PEG) as the hydrophilic block, and then examine the 5-FU release characteristics, pharmacokinetics, and anticancer effects of this novel compound. 5-FU loaded PEG-PBLG (5-FU/PEG-PBLG) nanoparticles were prepared by dialysis and then scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to observe the shape and size of the nanoparticles, and ultraviolet spectrophotometry was used to evaluate the 5-FU in vitro release characteristics. The pharmacokinetic parameters of 5-FU/PEG-PBLG nanoparticles in rabbit plasma were determined by measuring the 5-FUby high-performance liquid chromatography (HPLC). To study in vivo effects, LoVo cells (human colon cancer cell line) or Tca8113 cells (human oral squamous cell carcinoma cell line) were implanted in BALB/c nude mice that were subsequently treated with 5-FU or 5-FU/PEG-PBLG nanospheres. 5-FU/PEG-PBLG nanoparticles had a core-shell spherical structure with a diameter of 200 nm and a shell thickness of 30 nm. The drug loading capacity was 27.1% and the drug encapsulation was 61.5%. Compared with 5-FU, 5-FU/PEG-PBLG nanoparticles had a longer elimination half-life (t1/2, 33.3 h vs. 5 min), lower peak concentration (C, 4563.5 μg/L vs. 17047.3 μg/L), and greater distribution volume (VD, 0.114 L vs. 0.069 L). Compared with a blank control, LoVo cell xenografts and Tca8113 cell xenografts treated with 5-FU or 5-FU/PEG-PBLG nanoparticles grew slower and had prolonged tumor doubling times. 5-FU/PEG-PBLG nanoparticles showed greater inhibition of tumor growth than 5-FU (p < 0.01). In the PEG-PBLG nanoparticle control group, there was no tumor inhibition (p > 0.05). In our model

  1. The antioxidant and anticancer effects of wild carrot oil extract.

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    Shebaby, Wassim Nasri; El-Sibai, Mirvat; Smith, Kikki Bodman-; Karam, Marc Christoph; Mroueh, Mohamad; Daher, Costantine F

    2013-05-01

    Daucus carota L. ssp. carota (Apiacea) is used in traditional medicine in Lebanon and in different regions throughout the world. The present study investigates the in vitro anticancer activities of Daucus carota oil extract (DCOE) on four human cancer cell lines as well as its in vitro antioxidant activity. DCOE was extracted from the dried umbels with 50:50 acetone-methanol. The oil extract was analyzed by gas chromatography-mass spectrometry and screened for its antioxidant properties in vitro using 1,1-diphenyl-2-picryl hydrazyl free radical scavenging assay (DPPH), ferrous ion chelating assay (FIC) and the ferric reducing antioxidant power assay (FRAP). The anticancer activity of the oil extract against human colon (HT-29, Caco-2) and breast (MCF-7, MDA-MB-231) cancer cell lines was evaluated using the trypan blue exclusion method and the WST-1 cell proliferation assay. DCOE exhibited antioxidant activity in all assays used. The FRAP value was 164 ± 5.5 µmol FeSO4 /g, and the IC50 values for DPPH and FIC assays were 2.1 ± 0.03 mg/ml and 0.43 ± 0.02 mg/ml, respectively. Also, DCOE demonstrated a significant increase in cell death and decrease in cell proliferation. The effect of DCOE on the cell lines exhibited time and dose-dependent responses. The present study established that DCOE possesses both antioxidant and promising anticancer activities. PMID:22815230

  2. PPARs: Interference with Warburg’ Effect and Clinical Anticancer Trials

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    Joseph Vamecq

    2012-01-01

    Full Text Available The metabolic/cell signaling basis of Warburg’s effect (“aerobic glycolysis” and the general metabolic phenotype adopted by cancer cells are first reviewed. Several bypasses are adopted to provide a panoramic integrated view of tumoral metabolism, by attributing a central signaling role to hypoxia-induced factor (HIF-1 in the expression of aerobic glycolysis. The cancer metabolic phenotype also results from alterations of other routes involving ras, myc, p53, and Akt signaling and the propensity of cancer cells to develop signaling aberrances (notably aberrant surface receptor expression which, when present, offer unique opportunities for therapeutic interventions. The rationale for various emerging strategies for cancer treatment is presented along with mechanisms by which PPAR ligands might interfere directly with tumoral metabolism and promote anticancer activity. Clinical trials using PPAR ligands are reviewed and followed by concluding remarks and perspectives for future studies. A therapeutic need to associate PPAR ligands with other anticancer agents is perhaps an important lesson to be learned from the results of the clinical trials conducted to date.

  3. Anticancer effects of oligomeric proanthocyanidins on human colorectal cancer cell line, SNU-C4

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    Kim, Youn-Jung; Park, Hae-Jeong; Yoon, Seo-Hyun; Kim, Mi-Ja; Leem, Kang-hyun; Chung, Joo-Ho; Kim, Hye-Kyung

    2005-01-01

    AIM: Oligomeric proanthocyanidins (OPC), natural polyphenolic compounds found in plants, are known to have antioxidant and anti-cancer effects. We investigated whether the anti-cancer effects of the OPC are induced by apoptosis on human colorectal cancer cell line, SNU-C4.

  4. Anticancer Effect of Curcumin on B Cell non- Hodgkin's Lymphoma

    Institute of Scientific and Technical Information of China (English)

    SUN Chunyan; LIU Xinyue; CHEN Yan; LIU Fang

    2005-01-01

    To explore the anticancer effect of curcumin on human B cell non-Hodgkin's lymphoma and compare its effects on human B cell non-Hodgkin's lymphoma cells and normal peripheral blood mononuclear cells (NPBMNCs). MTT assay was used to study the effect of curcumin on the growth of Raji cells and NPBMNCs. The effect of curcumin on the apoptosis of Raji cells and NPBMNC were studied by flow cytometry and TDT-mediated dUTP nick and labeling (TUNEL). The effect of curcumin on the cell cycle of Raji cells were examined by propidium iodide staining flow cytometry. The results showed that curcumin strongly inhibited ±1.82 μmol/L and curcumin induced Raji cell apoptosis in a time- and dose-dependent manner. Raji cells treated with curcumin showed curcumin did not demonstrate apparent proliferation inhibition and apoptosis induction in NPBMNCs. It was concluded that curcumin is able to inhibit the proliferation of Raji cells by regulating the cell cycle and inducing the cell apoptosis. Morever, curcumin has low toxicity on NPBMNCs but can selectively induce apoptosis in Raji cells.

  5. Anti-cancer Effects of Phyllanthus urinaria and Relevant Mechanisms

    Directory of Open Access Journals (Sweden)

    Rong-Chi Yang

    2010-10-01

    Full Text Available Phyllanthus urinaria (P. urinaria, a widely used herbalmedicine, has been reported to possess various biologicalactivities. This report aimed to characterize the whole P. urinariaplant, present the anticancer effects of P. urinaria both invivo and in vitro, and explore relevant mechanisms. The waterextract of P. urinaria not only significantly reduces the cellviability of various cancer cell lines from different origins butalso suppresses tumor development in C57BL/6J mice afterimplantation of Lewis lung carcinoma (LCC cells. The anticanceractivity of P. urinaria extract is mainly due to inducedapoptosis of cancer cells as demonstrated by DNA fragmentationand increased caspase-3 activity through both intrinsic andextrinsic pathways. The decrease in viability with P. urinariatreatment might be partially associated with down-regulationof telomerase activation and induction of the apoptotic process.In addition, P. urinaria also exhibits anti-angiogenic activity that is mediated, at least in part,by suppression of matrix metalloproteinase 2 (MMP-2 secretion and inhibition of MMP-2activity through zinc chelation.

  6. Anticancer effects of the organosilicon multidrug resistance modulator SILA 421.

    Science.gov (United States)

    Olszewski, Ulrike; Zeillinger, Robert; Kars, Meltem Demirel; Zalatnai, Attila; Molnar, Jozsef; Hamilton, Gerhard

    2012-07-01

    1,3-dimethyl-1,3-bis(4-fluorophenyl)-1,3-bis{3-[1(4-butylpiperazinyl)]-propyl}-disiloxan-tetrahydrochlorid (SILA 421) is a compound that was developed as modulator of the ABC cassette transporter P-glycoprotein. Furthermore, it exerted antimicrobial toxicity, vascular effects, downregulation of chaperone induction and plasmid curing in bacterial cells. Here, this drug was found to possess cytotoxic activity against a panel of human cancer cell lines that do not overexpress P-gp, with 50% inhibitory concentrations ranging between 1.75±0.38 μM for GLC14 small cell lung cancer and 34.00±4.75 μM for PC-3 prostate cancer cells. HL-60 leukemia and MDA-MB-435 breast cancer cells exhibited cell cycle arrest and apoptotic cell death in response to SILA 421. Assessment of global gene expression of SILA 421-treated HL-60 cells was employed to identify cellular pathways affected by the compound and revealed disturbance of DNA replication, transcription and production of apparently misfolded proteins. Endoplasmatic reticulum stress and downregulation of cell cycle, cellular repair mechanisms and growth factor-related signaling cascades eventually resulted in induction of apoptosis in this cell line. In addition to the well established P-gp inhibitory effect of SILA compounds, reversal of resistance to taxanes, which had been reported for SILA 421 and the related molecule SILA 409, may be linked to downregulation of gene expression of kinesins. Interference with DNA replication and transcription seems to be the common denominator of antimicrobial activity and plasmid curing, as well as anticancer toxicity in human cell lines. Thus, in consideration of the full range of putative cellular targets found in the present work, the application of these SILA compounds for treatment of tumors should be further evaluated. PMID:22263791

  7. Potentiating effect of ecofriendly synthesis of copper oxide nanoparticles using brown alga: antimicrobial and anticancer activities

    Indian Academy of Sciences (India)

    SRI VISHNU PRIYA RAMASWAMY; S NARENDHRAN; RAJESHWARI SIVARAJ

    2016-04-01

    This study reports the in vitro antimicrobial and anticancer activities of biologically synthesized copper nanoparticles. The antimicrobial activity of green synthesized copper oxide nanoparticles was assessed by well diffusion method. The anticancer activity of brown algae-mediated copper oxide nanoparticles was determined by MTT assay against the cell line (MCF-7). Maximum activity was observed with Pseudomonas aeruginosa and Aspergillus niger. Effective growth inhibition of cells was observed to be more than 93% in antibacterial activity. Thus, the results of the present study indicates that biologically synthesized copper nanoparticles can be used for several diseases, however, it necessitates clinical studies to ascertain their potential as antimicrobial and anticancer agents.

  8. eQTL Regulating Transcript Levels Associated with Diverse Biological Processes in Tomato.

    Science.gov (United States)

    Ranjan, Aashish; Budke, Jessica M; Rowland, Steven D; Chitwood, Daniel H; Kumar, Ravi; Carriedo, Leonela; Ichihashi, Yasunori; Zumstein, Kristina; Maloof, Julin N; Sinha, Neelima R

    2016-09-01

    Variation in gene expression, in addition to sequence polymorphisms, is known to influence developmental, physiological, and metabolic traits in plants. Genetic mapping populations have facilitated identification of expression quantitative trait loci (eQTL), the genetic determinants of variation in gene expression patterns. We used an introgression population developed from the wild desert-adapted Solanum pennellii and domesticated tomato (Solanum lycopersicum) to identify the genetic basis of transcript level variation. We established the effect of each introgression on the transcriptome and identified approximately 7,200 eQTL regulating the steady-state transcript levels of 5,300 genes. Barnes-Hut t-distributed stochastic neighbor embedding clustering identified 42 modules revealing novel associations between transcript level patterns and biological processes. The results showed a complex genetic architecture of global transcript abundance pattern in tomato. Several genetic hot spots regulating a large number of transcript level patterns relating to diverse biological processes such as plant defense and photosynthesis were identified. Important eQTL regulating transcript level patterns were related to leaf number and complexity as well as hypocotyl length. Genes associated with leaf development showed an inverse correlation with photosynthetic gene expression, but eQTL regulating genes associated with leaf development and photosynthesis were dispersed across the genome. This comprehensive eQTL analysis details the influence of these loci on plant phenotypes and will be a valuable community resource for investigations on the genetic effects of eQTL on phenotypic traits in tomato. PMID:27418589

  9. Betulinic acid, a natural compound with potent anticancer effects

    NARCIS (Netherlands)

    F.B. Mullauer; J.H. Kessler; J.P. Medema

    2010-01-01

    New therapies using novel mechanisms to induce tumor cell death are needed with plants playing a crucial role as a source for potential anticancer compounds. One highly promising class of natural compounds are the triterpenoids with betulinic acid (BetA) as the most prominent representative. In-vitr

  10. Recent insights in nanotechnology-based drugs and formulations designed for effective anti-cancer therapy

    OpenAIRE

    Piktel, Ewelina; Niemirowicz, Katarzyna; Wątek, Marzena; Wollny, Tomasz; Deptuła, Piotr; Bucki, Robert

    2016-01-01

    The rapid development of nanotechnology provides alternative approaches to overcome several limitations of conventional anti-cancer therapy. Drug targeting using functionalized nanoparticles to advance their transport to the dedicated site, became a new standard in novel anti-cancer methods. In effect, the employment of nanoparticles during design of antineoplastic drugs helps to improve pharmacokinetic properties, with subsequent development of high specific, non-toxic and biocompatible anti...

  11. Recent insights in nanotechnology-based drugs and formulations designed for effective anti-cancer therapy.

    Science.gov (United States)

    Piktel, Ewelina; Niemirowicz, Katarzyna; Wątek, Marzena; Wollny, Tomasz; Deptuła, Piotr; Bucki, Robert

    2016-01-01

    The rapid development of nanotechnology provides alternative approaches to overcome several limitations of conventional anti-cancer therapy. Drug targeting using functionalized nanoparticles to advance their transport to the dedicated site, became a new standard in novel anti-cancer methods. In effect, the employment of nanoparticles during design of antineoplastic drugs helps to improve pharmacokinetic properties, with subsequent development of high specific, non-toxic and biocompatible anti-cancer agents. However, the physicochemical and biological diversity of nanomaterials and a broad spectrum of unique features influencing their biological action requires continuous research to assess their activity. Among numerous nanosystems designed to eradicate cancer cells, only a limited number of them entered the clinical trials. It is anticipated that progress in development of nanotechnology-based anti-cancer materials will provide modern, individualized anti-cancer therapies assuring decrease in morbidity and mortality from cancer diseases. In this review we discussed the implication of nanomaterials in design of new drugs for effective antineoplastic therapy and describe a variety of mechanisms and challenges for selective tumor targeting. We emphasized the recent advantages in the field of nanotechnology-based strategies to fight cancer and discussed their part in effective anti-cancer therapy and successful drug delivery. PMID:27229857

  12. Anticancer and antimetastatic effects of cordycepin, an active component of Cordyceps sinensis.

    Science.gov (United States)

    Nakamura, Kazuki; Shinozuka, Kazumasa; Yoshikawa, Noriko

    2015-01-01

    Cordyceps sinensis, a fungus that parasitizes on the larva of Lepidoptera, has been used as a valued traditional Chinese medicine. We investigated the effects of water extracts of Cordyceps sinensis (WECS), and particularly focused on its anticancer and antimetastatic actions. Based on in vitro studies, we report that WECS showed an anticancer action, and this action was antagonized by an adenosine A3 receptor antagonist. Moreover, this anticancer action of WECS was promoted by an adenosine deaminase inhibitor. These results suggest that one of the components of WECS with an anticancer action might be an adenosine or its derivatives. Therefore, we focused on cordycepin (3'-deoxyadenosine) as one of the active ingredients of WECS. According to our experiments, cordycepin showed an anticancer effect through the stimulation of adenosine A3 receptor, followed by glycogen synthase kinase (GSK)-3β activation and cyclin D1 suppression. Cordycepin also showed an antimetastatic action through inhibiting platelet aggregation induced by cancer cells and suppressing the invasiveness of cancer cells via inhibiting the activity of matrix metalloproteinase (MMP)-2 and MMP-9, and accelerating the secretion of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 from cancer cells. In conclusion, cordycepin, an active component of WECS, might be a candidate anticancer and antimetastatic agent. PMID:25704018

  13. Response of cbb gene transcription levels of four typical sulfur-oxidizing bacteria to the CO2 concentration and its effect on their carbon fixation efficiency during sulfur oxidation.

    Science.gov (United States)

    Wang, Ya-Nan; Wang, Lei; Tsang, Yiu Fai; Fu, Xiaohua; Hu, Jiajun; Li, Huan; Le, Yiquan

    2016-10-01

    The variability in carbon fixation capability of four sulfur-oxidizing bacteria (Thiobacillus thioparus DSM 505, Halothiobacillus neapolitanus DSM 15147, Starkeya novella DSM 506, and Thiomonas intermedia DSM 18155) during sulfur oxidation was studied at low and high concentrations of CO2. The mechanism underlying the variability in carbon fixation was clarified by analyzing the transcription of the cbb gene, which encodes the key enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase. DSM 15147 and DSM 505 fixed carbon more efficiently during sulfur oxidation than DSM 506 and DSM 18155 at 0.5% and 10% CO2, which was mainly because their cbb gene transcription levels were much higher than those of DSM 506 and DSM 18155. A high CO2 concentration significantly stimulated the carbon fixation efficiency of DSM 505 by greatly increasing the cbb gene transcription efficiency. Moreover, the influence of the CO2 concentration on the carbon fixation efficiency of the four strains differed greatly during sulfur oxidation. PMID:27542742

  14. Hormetic Effect of Berberine Attenuates the Anticancer Activity of Chemotherapeutic Agents.

    Directory of Open Access Journals (Sweden)

    Jiaolin Bao

    Full Text Available Hormesis is a phenomenon of biphasic dose response characterized by exhibiting stimulatory or beneficial effects at low doses and inhibitory or toxic effects at high doses. Increasing numbers of chemicals of various types have been shown to induce apparent hormetic effect on cancer cells. However, the underlying significance and mechanisms remain to be elucidated. Berberine, one of the major active components of Rhizoma coptidis, has been manifested with notable anticancer activities. This study aims to investigate the hormetic effect of berberine and its influence on the anticancer activities of chemotherapeutic agents. Our results demonstrated that berberine at low dose range (1.25 ~ 5 μM promoted cell proliferation to 112% ~170% of the untreated control in various cancer cells, while berberine at high dose rage (10 ~ 80 μM inhibited cell proliferation. Further, we observed that co-treatment with low dose berberine could significantly attenuate the anticancer activity of chemotherapeutic agents, including fluorouracil (5-FU, camptothecin (CPT, and paclitaxel (TAX. The hormetic effect and thereby the attenuated anticancer activity of chemotherapeutic drugs by berberine may attributable to the activated protective stress response in cancer cells triggered by berberine, as evidenced by up-regulated MAPK/ERK1/2 and PI3K/AKT signaling pathways. These results provided important information to understand the potential side effects of hormesis, and suggested cautious application of natural compounds and relevant herbs in adjuvant treatment of cancer.

  15. Metformin elicits anticancer effects through the sequential modulation of DICER and c-MYC.

    Science.gov (United States)

    Blandino, Giovanni; Valerio, Mariacristina; Cioce, Mario; Mori, Federica; Casadei, Luca; Pulito, Claudio; Sacconi, Andrea; Biagioni, Francesca; Cortese, Giancarlo; Galanti, Sergio; Manetti, Cesare; Citro, Gennaro; Muti, Paola; Strano, Sabrina

    2012-01-01

    Diabetic patients treated with metformin have a reduced incidence of cancer and cancer-related mortality. Here we show that metformin affects engraftment and growth of breast cancer tumours in mice. This correlates with the induction of metabolic changes compatible with clear anticancer effects. We demonstrate that microRNA modulation underlies the anticancer metabolic actions of metformin. In fact, metformin induces DICER expression and its effects are severely impaired in DICER knocked down cells. Conversely, ectopic expression of DICER recapitulates the effects of metformin in vivo and in vitro. The microRNAs upregulated by metformin belong mainly to energy metabolism pathways. Among the messenger RNAs downregulated by metformin, we found c-MYC, IRS-2 and HIF1alpha. Downregulation of c-MYC requires AMP-activated protein kinase-signalling and mir33a upregulation by metformin. Ectopic expression of c-MYC attenuates the anticancer metabolic effects of metformin. We suggest that DICER modulation, mir33a upregulation and c-MYC targeting have an important role in the anticancer metabolic effects of metformin. PMID:22643892

  16. Hormetic Effect of Berberine Attenuates the Anticancer Activity of Chemotherapeutic Agents

    OpenAIRE

    Jiaolin Bao; Borong Huang; Lidi Zou; Shenghui Chen; Chao Zhang; Yulin Zhang; Meiwan Chen; Jian-Bo Wan; Huanxing Su; Yitao Wang; Chengwei He

    2015-01-01

    Hormesis is a phenomenon of biphasic dose response characterized by exhibiting stimulatory or beneficial effects at low doses and inhibitory or toxic effects at high doses. Increasing numbers of chemicals of various types have been shown to induce apparent hormetic effect on cancer cells. However, the underlying significance and mechanisms remain to be elucidated. Berberine, one of the major active components of Rhizoma coptidis, has been manifested with notable anticancer activities. This st...

  17. Potent Anticancer Effects of Bioactive Mushroom Extracts (Phellinus linteus) on a Variety of Human Cancer Cells

    OpenAIRE

    Konno, Sensuke; Chu, Kevin; Feuer, Nicholas; Phillips, John; Choudhury, Muhammad

    2014-01-01

    Background Although several therapeutic options are currently available for patients with various cancers, the outcomes are often disappointing and a more effective modality needs to be promptly established. We have been exploring an alternative approach using natural agents and two bioactive mushroom extracts isolated from Phellinus linteus (PL), namely PL-ES and PL-I-ES, were of our interest. As anticancer effects of similar extracts have been reported in several cancers, we investigated wh...

  18. Low-intensity continuous ultrasound triggers effective bisphosphonate anticancer activity in breast cancer

    OpenAIRE

    Sophie Tardoski; Jacqueline Ngo; Evelyne Gineyts; Jean-Paul Roux; Philippe Clézardin; David Melodelima

    2015-01-01

    Ultrasound (US) is a non-ionizing pressure wave that can produce mechanical and thermal effects. Bisphosphonates have demonstrated clinical utility in bone metastases treatment. Preclinical studies suggest that bisphosphonates have anticancer activity. However, bisphosphonates exhibit a high affinity for bone mineral, which reduces their bioavailibity for tumor cells. Ultrasound has been shown to be effective for drug delivery but in interaction with gas bubbles or encapsulated drugs. We exam...

  19. CrBPF1 overexpression alters transcript levels of terpenoid indole alkaloid biosynthetic and regulatory genes.

    Science.gov (United States)

    Li, Chun Yao; Leopold, Alex L; Sander, Guy W; Shanks, Jacqueline V; Zhao, Le; Gibson, Susan I

    2015-01-01

    Terpenoid indole alkaloid (TIA) biosynthesis in Catharanthus roseus is a complex and highly regulated process. Understanding the biochemistry and regulation of the TIA pathway is of particular interest as it may allow the engineering of plants to accumulate higher levels of pharmaceutically important alkaloids. Toward this end, we generated a transgenic C. roseus hairy root line that overexpresses the CrBPF1 transcriptional activator under the control of a β-estradiol inducible promoter. CrBPF1 is a MYB-like protein that was previously postulated to help regulate the expression of the TIA biosynthetic gene STR. However, the role of CrBPF1 in regulation of the TIA and related pathways had not been previously characterized. In this study, transcriptional profiling revealed that overexpression of CrBPF1 results in increased transcript levels for genes from both the indole and terpenoid biosynthetic pathways that provide precursors for TIA biosynthesis, as well as for genes in the TIA biosynthetic pathway. In addition, overexpression of CrBPF1 causes increases in the transcript levels for 11 out of 13 genes postulated to act as transcriptional regulators of genes from the TIA and TIA feeder pathways. Interestingly, overexpression of CrBPF1 causes increased transcript levels for both TIA transcriptional activators and repressors. Despite the fact that CrBPF1 overexpression affects transcript levels of a large percentage of TIA biosynthetic and regulatory genes, CrBPF1 overexpression has only very modest effects on the levels of the TIA metabolites analyzed. This finding may be due, at least in part, to the up-regulation of both transcriptional activators and repressors in response to CrBPF1 overexpression, suggesting that CrBPF1 may serve as a "fine-tune" regulator for TIA biosynthesis, acting to help regulate the timing and amplitude of TIA gene expression. PMID:26483828

  20. CrBPF1 overexpression alters transcript levels of terpenoid indole alkaloid biosynthetic and regulatory genes

    Directory of Open Access Journals (Sweden)

    Chun Yao eLi

    2015-10-01

    Full Text Available Terpenoid indole alkaloid (TIA biosynthesis in Catharanthus roseus is a complex and highly regulated process. Understanding the biochemistry and regulation of the TIA pathway is of particular interest as it may allow the engineering of plants to accumulate higher levels of pharmaceutically important alkaloids. Towards this end, we generated a transgenic C. roseus hairy root line that overexpresses the CrBPF1 transcriptional activator under the control of a β-estradiol inducible promoter. CrBPF1 is a MYB-like protein that was previously postulated to help regulate the expression of the TIA biosynthetic gene STR. However, the role of CrBPF1 in regulation of the TIA and related pathways had not been previously characterized. In this study, transcriptional profiling revealed that overexpression of CrBPF1 results in increased transcript levels for genes from both the indole and terpenoid biosynthetic pathways that provide precursors for TIA biosynthesis, as well as for genes in the TIA biosynthetic pathway. In addition, overexpression of CrBPF1 causes increases in the transcript levels for 11 out of 13 genes postulated to act as transcriptional regulators of genes from the TIA and TIA feeder pathways. Interestingly, overexpression of CrBPF1 causes increased transcript levels for both TIA transcriptional activators and repressors. Despite the fact that CrBPF1 overexpression affects transcript levels of a large percentage of TIA biosynthetic and regulatory genes, CrBPF1 overexpression has only very modest effects on the levels of the TIA metabolites analyzed. This finding may be due, at least in part, to the up-regulation of both transcriptional activators and repressors in response to CrBPF1 overexpression, suggesting that CrBPF1 may serve as a fine-tune regulator for TIA biosynthesis, acting to help regulate the timing and amplitude of TIA gene expression.

  1. Calcium regulates caveolin-1 expression at the transcriptional level

    International Nuclear Information System (INIS)

    Highlights: ► Caveolin-1 expression is regulated by calcium signaling at the transcriptional level. ► An inhibitor of or siRNA to L-type calcium channel suppressed caveolin-1 expression. ► Cyclosporine A or an NFAT inhibitor markedly reduced caveolin-1 expression. ► Caveolin-1 regulation by calcium signaling is observed in several mouse cell lines. -- Abstract: Caveolin-1, an indispensable component of caveolae serving as a transformation suppressor protein, is highly expressed in poorly metastatic mouse osteosarcoma FBJ-S1 cells while highly metastatic FBJ-LL cells express low levels of caveolin-1. Calcium concentration is higher in FBJ-S1 cells than in FBJ-LL cells; therefore, we investigated the possibility that calcium signaling positively regulates caveolin-1 in mouse FBJ-S1 cells. When cells were treated with the calcium channel blocker nifedipine, cyclosporin A (a calcineurin inhibitor), or INCA-6 (a nuclear factor of activated T-cells [NFAT] inhibitor), caveolin-1 expression at the mRNA and protein levels decreased. RNA silencing of voltage-dependent L-type calcium channel subunit alpha-1C resulted in suppression of caveolin-1 expression. This novel caveolin-1 regulation pathway was also identified in mouse NIH 3T3 cells and Lewis lung carcinoma cells. These results indicate that caveolin-1 is positively regulated at the transcriptional level through a novel calcium signaling pathway mediated by L-type calcium channel/Ca2+/calcineurin/NFAT.

  2. Fucoxanthin: A Marine Carotenoid Exerting Anti-Cancer Effects by Affecting Multiple Mechanisms

    OpenAIRE

    Sangeetha Ravi Kumar; Masashi Hosokawa; Kazuo Miyashita

    2013-01-01

    Fucoxanthin is a marine carotenoid exhibiting several health benefits. The anti-cancer effect of fucoxanthin and its deacetylated metabolite, fucoxanthinol, is well documented. In view of its potent anti-carcinogenic activity, the need to understand the underlying mechanisms has gained prominence. Towards achieving this goal, several researchers have carried out studies in various cell lines and in vivo and have deciphered that fucoxanthin exerts its anti-proliferative and cancer preventing ...

  3. Phenolcarboxylic acids from medicinal herbs exert anticancer effects through disruption of COX-2 activity.

    Science.gov (United States)

    Tao, Li; Wang, Sheng; Zhao, Yang; Sheng, Xiaobo; Wang, Aiyun; Zheng, Shizhong; Lu, Yin

    2014-09-25

    Integrated research of herbs and formulas characterized by functions of promoting blood circulation and removing blood stasis is one of the most active fields in traditional Chinese medicine. This paper strives to demonstrate the roles of a homologous series of phenolcarboxylic acids from these medicinal herbs in cancer treatment via targeting cyclooxygenase-2 (COX-2), a well-recognized mediator in tumorigenesis. We selected thirteen typical phenolcarboxylic acids (benzoic acid derivatives, cinnamic acid derivatives and their dehydration-condensation products), and found gallic acid, caffeic acid, danshensu, rosmarinic acid and salvianolic acid B showed 50% inhibitory effects on hCOX-2 activity and A549 cells proliferation. 2D-quantitative method was introduced to describe the potential structural features that contributed to certain bioactivities. We also found these compounds underwent responsible hydrogen bonding to Arg120 and Ser353 in COX-2 active site residues. We further extensively focused on danshensu [d-(+)-β-(3,4-dihydoxy-phenylalanine)] or DSS, which exerted COX-2 dependent anticancer manner. Both genetic and pharmacological inhibition of COX-2 could enhance the ability of DSS inhibiting A549 cells growth. Additionally, COX-2/PGE2/ERK signaling axis was essential for the anticancer effect of DSS. Furthermore, combined treatment with DSS and celecoxib could produce stronger anticancer effects in experimental lung metastasis of A549 cells in vivo. All these findings indicated that phenolcarboxylic acids might possess anticancer effects through jointly targeting COX-2 activity in cancer cells and provided strong evidence in cancer prevention and therapy for the herbs characterized by blood-activating and stasis-resolving functions in clinic. PMID:24916702

  4. Nanofabrication of methylglyoxal with chitosan biopolymer: a potential tool for enhancement of its anticancer effect

    OpenAIRE

    Pal, Aparajita; Talukdar, Dipa; Roy, Anirban; Ray, Subhankar; Mallick, Asish; Mandal, Chitra; Ray, Manju

    2015-01-01

    Purpose The normal metabolite methylglyoxal (MG) specifically kills cancer cells by inhibiting glycolysis and mitochondrial respiration without much adverse effect upon normal cells. Though the anticancer property of MG is well documented, its gradual enzymatic degradation in vivo has prompted interest in developing a nanoparticulate drug delivery system to protect it and also to enhance its efficacy. Materials and methods MG-conjugated chitosan nanoparticles (Nano-MG) were prepared by conjug...

  5. Anticancer Effects of Sinulariolide-Conjugated Hyaluronan Nanoparticles on Lung Adenocarcinoma Cells

    Directory of Open Access Journals (Sweden)

    Kuan Yin Hsiao

    2016-03-01

    Full Text Available Lung cancer is one of the most clinically challenging malignant diseases worldwide. Sinulariolide (SNL, extracted from the farmed coral species Sinularia flexibilis, has been used for suppressing malignant cells. For developing anticancer therapeutic agents, we aimed to find an alternative for non-small cell lung cancer treatment by using SNL as the target drug. We investigated the SNL bioactivity on A549 lung cancer cells by conjugating SNL with hyaluronan nanoparticles to form HA/SNL aggregates by using a high-voltage electrostatic field system. SNL was toxic on A549 cells with an IC50 of 75 µg/mL. The anticancer effects of HA/SNL aggregates were assessed through cell viability assay, apoptosis assays, cell cycle analyses, and western blotting. The size of HA/SNL aggregates was approximately 33–77 nm in diameter with a thin continuous layer after aggregating numerous HA nanoparticles. Flow cytometric analysis revealed that the HA/SNL aggregate-induced apoptosis was more effective at a lower SNL dose of 25 µg/mL than pure SNL. Western blotting indicated that caspases-3, -8, and -9 and Bcl-xL and Bax played crucial roles in the apoptotic signal transduction pathway. In summary, HA/SNL aggregates exerted stronger anticancer effects on A549 cells than did pure SNL via mitochondria-related pathways.

  6. Mistletoe treatments for minimising side effects of anticancer chemotherapy

    Directory of Open Access Journals (Sweden)

    Busse, Reinhard

    2006-09-01

    Full Text Available Background: More than 200,000 persons died in 2002 in Germany as a consequence of cancer diseases. Cancer (ICD-9: 140-208, ICD-10: C00-C97 accounted for 28% of all male deaths and for 22% of all female deaths. Cancer treatment consists on surgery, radio- and chemotherapy. During chemotherapy patients may experience a wide variety of toxic effects (including life-threatening toxicity which require treatment. The type and the intensity of chemotherapy toxicity are one of the limiting factors in cancer treatment. Toxic effects are also one of the factors affecting health related quality of life (HRQOL during chemotherapy. Mistletoe extracts belong to the group of so called „unconventional methods“ and are used in Germany as complementary cancer treatments. It has been postulated that the addition of mistletoe to chemotherapeutical regimes could help reduce chemotherapy-induced toxicity and enhance treatment tolerability. The German social health insurance covers the prescription of ML I standardized mistletoe extracts when those are prescribed as palliative cancer treatments with the aim of improving HRQOL. Research questions: * Does the addition of mistletoe to chemotherapeutical regimes reduce their toxicity? * Does the addition of mistletoe to chemotherapeutical regimes contribute to improve quality of life? * Has the addition of mistletoe to chemotherapeutical regimes any effects on survival? * Has the addition of mistletoe to chemotherapeutical regimes any effects on tumor-remission? Methods: We conducted a systematic literature search in following databases: The Cochrane Library, DIMDI Superbase and Dissertation Abstracts. We included systematic reviews and randomized controlled trials (RCT. Appraisal of literature was done by two authors independently. Checklists were used to guide literature appraisal. The Jadad-Score was used to score quality of RCT. Evidence was summarized in tables and in narrative form. Results and discussion: The

  7. Multiple Mechanisms of Anti-Cancer Effects Exerted by Astaxanthin

    OpenAIRE

    Li Zhang; Handong Wang

    2015-01-01

    Astaxanthin (ATX) is a xanthophyll carotenoid which has been approved by the United States Food and Drug Administration (USFDA) as food colorant in animal and fish feed. It is widely found in algae and aquatic animals and has powerful anti-oxidative activity. Previous studies have revealed that ATX, with its anti-oxidative property, is beneficial as a therapeutic agent for various diseases without any side effects or toxicity. In addition, ATX also shows preclinical anti-tumor efficacy both i...

  8. Potentiation of Anticancer Drugs: Effects of Pentoxifylline on Neoplastic Cells

    Directory of Open Access Journals (Sweden)

    Miroslav Barancik

    2011-12-01

    Full Text Available The drug efflux activity of P-glycoprotein (P-gp, a product of the mdr1 gene, ABCB1 member of ABC transporter family represents a mechanism by which tumor cells escape death induced by chemotherapeutics. In this study, we investigated the mechanisms involved in the effects of pentoxifylline (PTX on P-gp-mediated multidrug resistance (MDR in mouse leukemia L1210/VCR cells. Parental sensitive mouse leukemia cells L1210, and multidrug-resistant cells, L1210/VCR, which are characterized by the overexpression of P-gp, were used as experimental models. The cells were exposed to 100 μmol/L PTX in the presence or absence of 1.2 μmol/L vincristine (VCR. Western blot analysis indicated a downregulation of P-gp protein expression when multidrug-resistant L1210/VCR cells were exposed to PTX. The effects of PTX on the sensitization of L1210/VCR cells to VCR correlate with the stimulation of apoptosis detected by Annexin V/propidium iodide apoptosis necrosis kit and proteolytic activation of both caspase-3 and caspase-9 monitored by Western blot analysis. Higher release of matrix metalloproteinases (MMPs, especially MMP-2, which could be attenuated by PTX, was found in L1210/VCR than in L1210 cells by gelatin zymography in electrophoretic gel. Exposure of resistant cells to PTX increased the content of phosphorylated Akt kinase. In contrast, the presence of VCR eliminated the effects of PTX on Akt kinase phosphorylation. Taken together, we conclude that PTX induces the sensitization of multidrug-resistant cells to VCR via downregulation of P-gp, stimulation of apoptosis and reduction of MMPs released from drug-resistant L1210/VCR cells. These facts bring new insights into the mechanisms of PTX action on cancer cells.

  9. Mistletoe treatments for minimising side effects of anticancer chemotherapy

    OpenAIRE

    Busse, Reinhard; Velasco Garrido, Marcial; Lange-Lindberg, Anna-Maria

    2006-01-01

    Background: More than 200,000 persons died in 2002 in Germany as a consequence of cancer diseases. Cancer (ICD-9: 140-208, ICD-10: C00-C97) accounted for 28% of all male deaths and for 22% of all female deaths. Cancer treatment consists on surgery, radio- and chemotherapy. During chemotherapy patients may experience a wide variety of toxic effects (including life-threatening toxicity) which require treatment. The type and the intensity of chemotherapy toxicity are one of the limiting factors ...

  10. Calcium regulates caveolin-1 expression at the transcriptional level

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Xiao-Yan; Huang, Cheng-Cheng; Kan, Qi-Ming [Laboratory of Tumor Biology and Glycobiology, Department of Life Sciences, Shenyang Pharmaceutical University, Shenyang 110016, People' s Republic of China (China); Li, Yan [Experimental Animal Center, Department of Life Sciences, Shenyang Pharmaceutical University, Shenyang 110016, People' s Republic of China (China); Liu, Dan; Zhang, Xue-Cheng [Laboratory of Tumor Biology and Glycobiology, Department of Life Sciences, Shenyang Pharmaceutical University, Shenyang 110016, People' s Republic of China (China); Sato, Toshinori [Department of Biosciences and Informatics, Keio University, Hiyoshi, Yokohama 223-8522 (Japan); Yamagata, Sadako [Laboratory of Tumor Biology and Glycobiology, Department of Life Sciences, Shenyang Pharmaceutical University, Shenyang 110016, People' s Republic of China (China); Yamagata, Tatsuya, E-mail: tcyamagata@gmail.com [Laboratory of Tumor Biology and Glycobiology, Department of Life Sciences, Shenyang Pharmaceutical University, Shenyang 110016, People' s Republic of China (China)

    2012-09-28

    Highlights: Black-Right-Pointing-Pointer Caveolin-1 expression is regulated by calcium signaling at the transcriptional level. Black-Right-Pointing-Pointer An inhibitor of or siRNA to L-type calcium channel suppressed caveolin-1 expression. Black-Right-Pointing-Pointer Cyclosporine A or an NFAT inhibitor markedly reduced caveolin-1 expression. Black-Right-Pointing-Pointer Caveolin-1 regulation by calcium signaling is observed in several mouse cell lines. -- Abstract: Caveolin-1, an indispensable component of caveolae serving as a transformation suppressor protein, is highly expressed in poorly metastatic mouse osteosarcoma FBJ-S1 cells while highly metastatic FBJ-LL cells express low levels of caveolin-1. Calcium concentration is higher in FBJ-S1 cells than in FBJ-LL cells; therefore, we investigated the possibility that calcium signaling positively regulates caveolin-1 in mouse FBJ-S1 cells. When cells were treated with the calcium channel blocker nifedipine, cyclosporin A (a calcineurin inhibitor), or INCA-6 (a nuclear factor of activated T-cells [NFAT] inhibitor), caveolin-1 expression at the mRNA and protein levels decreased. RNA silencing of voltage-dependent L-type calcium channel subunit alpha-1C resulted in suppression of caveolin-1 expression. This novel caveolin-1 regulation pathway was also identified in mouse NIH 3T3 cells and Lewis lung carcinoma cells. These results indicate that caveolin-1 is positively regulated at the transcriptional level through a novel calcium signaling pathway mediated by L-type calcium channel/Ca{sup 2+}/calcineurin/NFAT.

  11. Synergistic enhancement effect of magnetic nanoparticles on anticancer drug accumulation in cancer cells

    Science.gov (United States)

    Zhang, Renyun; Wang, Xuemei; Wu, Chunhui; Song, Min; Li, Jingyuan; Lv, Gang; Zhou, Jian; Chen, Chen; Dai, Yongyuan; Gao, Feng; Fu, Degang; Li, Xiaomao; Guan, Zhiqun; Chen, Baoan

    2006-07-01

    Three kinds of magnetic nanoparticle, tetraheptylammonium capped nanoparticles of Fe3O4, Fe2O3 and Ni have been synthesized, and the synergistic effect of these nanoparticles on the drug accumulation of the anticancer drug daunorubicin in leukaemia cells has been explored. Our observations indicate that the enhancement effect of Fe3O4 nanoparticles is much stronger than that of Fe2O3 and Ni nanoparticles, suggesting that nanoparticle surface chemistry and size as well as the unique properties of the magnetic nanoparticles themselves may contribute to the synergistic enhanced effect of the drug uptake of targeted cancer cells.

  12. Multiple Mechanisms of Anti-Cancer Effects Exerted by Astaxanthin

    Directory of Open Access Journals (Sweden)

    Li Zhang

    2015-07-01

    Full Text Available Astaxanthin (ATX is a xanthophyll carotenoid which has been approved by the United States Food and Drug Administration (USFDA as food colorant in animal and fish feed. It is widely found in algae and aquatic animals and has powerful anti-oxidative activity. Previous studies have revealed that ATX, with its anti-oxidative property, is beneficial as a therapeutic agent for various diseases without any side effects or toxicity. In addition, ATX also shows preclinical anti-tumor efficacy both in vivo and in vitro in various cancer models. Several researches have deciphered that ATX exerts its anti-proliferative, anti-apoptosis and anti-invasion influence via different molecules and pathways including signal transducer and activator of transcription 3 (STAT3, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB and peroxisome proliferator-activated receptor gamma (PPARγ. Hence, ATX shows great promise as chemotherapeutic agents in cancer. Here, we review the rapidly advancing field of ATX in cancer therapy as well as some molecular targets of ATX.

  13. Green Chemistry Approach for Synthesis of Effective Anticancer Palladium Nanoparticles.

    Science.gov (United States)

    Gurunathan, Sangiliyandi; Kim, EunSu; Han, Jae Woong; Park, Jung Hyun; Kim, Jin-Hoi

    2015-01-01

    The purpose of this study was to design and synthesize Palladium nanoparticles (PdNPs) using an environmentally friendly approach and evaluate the in vitro efficacy of PdNPs in human ovarian cancer A2780 cells. Ultraviolet-Visible (UV-Vis) spectroscopy was used to monitor the conversion of Pd(II) ions to Pd(0)NPs. X-ray diffraction (XRD) revealed the crystallinity of the as-synthesized PdNPs and Fourier transform infrared spectroscopy (FTIR) further confirmed the role of the leaf extract of Evolvulus alsinoides as a reducing and stabilizing agent for the synthesis of PdNPs. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) showed that the average size of the NPs was 5 nm. After a 24-h exposure to PdNPs, cell viability and light microscopy assays revealed the dose-dependent toxicity of the PdNPs. Furthermore, the dose-dependent cytotoxicity of the PdNPs was confirmed by lactate dehydrogenase (LDH), increased reactive oxygen species (ROS) generation, activation of PdNPs-induced autophagy, impairment of mitochondrial membrane potential (MMP), enhanced caspase-3 activity, and detection of TUNEL-positive cells. Our study demonstrates a single, simple, dependable and green approach for the synthesis of PdNPs using leaf extracts of Evolvulus alsinoides. Furthermore, the in vitro efficacy of PdNPs in human ovarian cancer cells suggests that it could be an effective therapeutic agent for cancer therapy. PMID:26694334

  14. Anticancer effects of four varieties of muscadine grape.

    Science.gov (United States)

    God, Jason M; Tate, Patricia; Larcom, Lyndon L

    2007-03-01

    The initiating event in carcinogenesis is a somatic mutation. During progression of the disease, additional mutations accumulate as the transformed cells develop the ability to proliferate and metastasize. These mutations can be produced by reactive oxygen species (ROS) generated through metabolism, or environmental insult. Metastasis involves tissue degradative enzymes, many of which are members of the matrix metalloproteinase family. Hence, substances that can neutralize ROS, inhibit mutagenesis, or block activity of the matrix metalloproteinases should prove to be anticarcinogenic. This study was performed to evaluate the possible anticarcinogenic characteristics of muscadine grapes. These grow wild in the southeast United States and have not been subjected to extensive breeding, as have most commercially cultivated fruits. The extracts tested were from pomace remaining after wine production. This is usually discarded, but the results obtained in this study indicate that pomace water extracts could be used as sources for purification of anticarcinogenic compounds. Four varieties of muscadine grape were tested for their abilities to affect mutagenesis by the metabolically activated carcinogen 2-aminoanthracene. Each extract was also assayed for antioxidant activity and for its ability to inhibit activity of matrix metalloproteinases-2 and -9. Each of the four extracts showed significant inhibition of 2-aminoanthracene mutagenesis, high antioxidant activity, and the ability to inhibit activities of both metalloproteinases, implying that these extracts could be good inhibitors of carcinogenesis. Two of the extracts showed little activity when tested for their effects on mutagenesis by the direct-acting mutagen methyl methanesulfonate. PMID:17472467

  15. Green Chemistry Approach for Synthesis of Effective Anticancer Palladium Nanoparticles

    Directory of Open Access Journals (Sweden)

    Sangiliyandi Gurunathan

    2015-12-01

    Full Text Available The purpose of this study was to design and synthesize Palladium nanoparticles (PdNPs using an environmentally friendly approach and evaluate the in vitro efficacy of PdNPs in human ovarian cancer A2780 cells. Ultraviolet-Visible (UV-Vis spectroscopy was used to monitor the conversion of Pd(II ions to Pd(0NPs. X-ray diffraction (XRD revealed the crystallinity of the as-synthesized PdNPs and Fourier transform infrared spectroscopy (FTIR further confirmed the role of the leaf extract of Evolvulus alsinoides as a reducing and stabilizing agent for the synthesis of PdNPs. Dynamic light scattering (DLS and transmission electron microscopy (TEM showed that the average size of the NPs was 5 nm. After a 24-h exposure to PdNPs, cell viability and light microscopy assays revealed the dose-dependent toxicity of the PdNPs. Furthermore, the dose-dependent cytotoxicity of the PdNPs was confirmed by lactate dehydrogenase (LDH, increased reactive oxygen species (ROS generation, activation of PdNPs-induced autophagy, impairment of mitochondrial membrane potential (MMP, enhanced caspase-3 activity, and detection of TUNEL-positive cells. Our study demonstrates a single, simple, dependable and green approach for the synthesis of PdNPs using leaf extracts of Evolvulus alsinoides. Furthermore, the in vitro efficacy of PdNPs in human ovarian cancer cells suggests that it could be an effective therapeutic agent for cancer therapy.

  16. Metformin exerts anticancer effects through the inhibition of the Sonic hedgehog signaling pathway in breast cancer.

    Science.gov (United States)

    Fan, Cong; Wang, Yunshan; Liu, Ziming; Sun, Ying; Wang, Xiuwen; Wei, Guangwei; Wei, Junmin

    2015-07-01

    Metformin, a widely prescribed antidiabetic drug, has previously been shown to lower the risk of certain types of cancer, including that of breast cancer, and to improve prognosis. Its anticancer effects, which are mediated by the activation of AMP-activated protein kinase (AMPK), have become notable. The Sonic hedgehog (Shh) signaling pathway is involved in changes in mammary ducts and malignant transformation. The aim of the present study was to elucidate the role of the Shh pathway in mediating the anticancer effects of metformin and the correlation between AMPK and the Shh pathway. We investigated the effectiveness of metformin in inhibiting the proliferation, migration, invasion and stemness of breast cancer cells in vitro using RNA extraction and reverse transcription‑polymerase chain reaction (RT-PCR), western blot analysis, cell proliferation assay, scratch-wound assay (cell migration assay), cell invasion assay, mammosphere culture and flow cytometry. In in vivo experiments, a tumor xenograft model was used to detect the effects of metformin on cancer cell proliferation. The results revealed that the treatment of breast cancer cells with metformin led to the inhibition of the Shh signaling pathway. Importantly, metformin inhibited recombinant human Shh (rhShh)‑induced cell migration, invasion, and stemness, and impaired cell proliferation both in vitro and in vivo. Furthermore, the small interfering RNA (siRNA)‑mediated downregulation of AMPK reversed the inhibitory effects of metformin on rhShh‑induced Gli-1 expression and stemness. Our findings identified a role of the Shh signaling pathway in the anticancer effects of metformin in breast cancer. Furthermore, we revealed that the metformin-mediated inhibition of the Shh signaling pathway may be dependent on AMPK. PMID:25999130

  17. Synergistic anticancer effect of the extracts from Polyalthia evecta caused apoptosis in human hepatoma (HepG2) cells

    Institute of Scientific and Technical Information of China (English)

    Sasipawan Machana; Natthida Weerapreeyakul; Sahapat Barusrux; Kanjana Thumanu; Waraporn Tanthanuch

    2012-01-01

    Objective: To evaluate the anticancer activity of the extract fraction of Polyalthia evecta (P. evecta) (Pierre) Finet & Gagnep and the synergistic anticancer effect of the extracts from P. evecta by using the ATR/FT-IR spectroscopy. Methods: The 50% ethanol-water crude leaf extract of P. evecta (EW-L) was prepared and was further fractionated to isolate various fractions. The anticancer activity was investigated from cytotoxicity against HepG2 using a neutral red assay and apoptosis induction by evaluation of nuclei morphological changes after DAPI staining. Synergistic anticancer effects of the extracts from P. evecta were performed using the ATR/FT-IR spectroscopy. Results: The result showed that the EW-L showed higher cytotoxicity and apoptosis induction in HepG2 cells than its fractionated extracts. The hexane extract exhibited higher cytotoxicity and apoptosis induction than the water extracts, but less than the EW-L. The combined water and hexane extracts apparently increased cytotoxicity and apoptosis induction. The %apoptotic cells induced by the extract mixture were increased about 2-fold compared to the single hexane extract. Conclusions: The polar extract fraction is necessary for the anticancer activity of the non-polar extract fraction. The ATR/FT-IR spectra illustrates the physical interaction among the constituents in the extract mixture and reveals the presence of polyphenolic constituents in the EW-L, which might play a role for the synergistic anticancer effect.

  18. Synergistic anticancer effects of curcumin and resveratrol in Hepa1-6 hepatocellular carcinoma cells.

    Science.gov (United States)

    Du, Qin; Hu, Bing; An, Hong-Mei; Shen, Ke-Ping; Xu, Ling; Deng, Shan; Wei, Meng-Meng

    2013-05-01

    Hepatocellular carcinoma remains one of the most prevalent malignancies worldwide. Curcuma aromatica and Polygonum cuspidatum are one of the commonly used paired-herbs for liver cancer treatment. Curcumin and resveratrol are the major anticancer constituents of Curcuma aromatica and Polygonum cuspidatum, respectively. Curcumin and resveratrol have been found to exhibit a synergistic anticancer effect in colon cancer. However, the combined effect of curcumin and resveratrol against hepatocellular carcinoma remains unknown. In the present study, we evaluated the combined effects of curcumin and resveratrol in hepatocellular carcinoma Hepa1-6 cells. The results showed that curcumin and resveratrol significantly inhibited the proliferation of Hepa1-6 cells in a dose- and time-dependent manner. The combination treatment of curcumin and resveratrol elicited a synergistic antiproliferative effect in Hepa1-6 cells. The apoptosis of Hepa1-6 cells induced by the combination treatment with curcumin and resveratrol was accompanied by caspase-3, -8 and -9 activation, which was completely abrogated by a pan caspase inhibitor, Z-VAD-FMK. Combination of curcumin and resveratrol upregulated intracellular reactive oxygen species (ROS) levels in Hepa1-6 cells. The ROS scavenger, NAC, partially attenuated the apoptosis and caspase activation induced by the combination treatment of curcumin and resveratrol. In addition, the combination of curcumin and resveratrol downregulated XIAP and survivin expression. These data suggest that the combination treatment of curcumin and resveratrol is a promising novel anticancer strategy for liver cancer. The present study also provides new insights into the effective mechanism of paired-herbs in traditional Chinese medicine. PMID:23446753

  19. Anticancer chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Weller, R.E.

    1988-10-01

    Despite troubled beginnings, anticancer chemotherapy has made significant contribution to the control of cancer in man, particularly within the last two decades. Early conceptual observations awakened the scientific community to the potentials of cancer chemotherapy. There are now more than 50 agents that are active in causing regression of clinical cancer. Chemotherapy's major conceptual contributions are two-fold. First, there is now proof that patients with overt metastatic disease can be cured, and second, to provide a strategy for control of occult metastases. In man, chemotherapy has resulted in normal life expectancy for some patients who have several types of metastatic cancers, including choriocarcinoma, Burkitt's lymphomas, Wilm's tumor, acute lymphocytic leukemia, Hodgkins disease, diffuse histiocytic lymphoma and others. Anticancer chemotherapy in Veterinary medicine has evolved from the use of single agents, which produce only limited remissions, to the concept of combination chemotherapy. Three basic principles underline the design of combination chemotherapy protocols; the fraction of tumor cell killed by one drug is independent of the fraction killed by another drug; drugs with different mechanisms of action should be chosen so that the antitumor effects will be additive; and since different classes of drugs have different toxicities the toxic effects will not be additive.

  20. Anti-Cancer Effects of Green Tea by Either Anti- or Pro- Oxidative Mechanisms.

    Science.gov (United States)

    Hayakawa, Sumio; Saito, Kieko; Miyoshi, Noriyuki; Ohishi, Tomokazu; Oishi, Yumiko; Miyoshi, Mamoru; Nakamura, Yoriyuki

    2016-01-01

    Tea derived from the leaves and buds of Camellia sinensis (Theaceae) is consumed worldwide. Green tea contains various components with specific health-promoting effects, and is believed to exert protective effects against diseases including cancer, diabetes and hepatitis, as well as obesity. Of the various tea components, the polyphenol catechins have been the subject of extensive investigation and among the catechins, (-)-epigallocatechin gallate has the strongest bioactivity in most cases. Our research group has postulated that hepatocyte nuclear factor-4α, sterol regulatory element-binding proteins, and tumor necrosis factor-α are targets of green tea constituents including (-)-epigallocatechin gallate for their anti-diabetes, anti-obesity, and anti-hepatitis effects, respectively. Published papers were reviewed to determine whether the observed changes in these factors can be correlated with anti-cancer effects of green tea. Two major action mechanisms of (-)-epigallocatechin gallate have been proposed; one associated with its anti-oxidative properties and the other with its pro-oxidative activity. When reactive oxygen species are assumed to be involved, our findings that (-)-epigallocatechin gallate down- regulated hepatocyte nuclear factor-4α, sterol regulatory element-binding proteins, and tumor necrosis factor-α may explain the anti-cancer effect of green tea as well. However, further studies are required to elucidate which determinant directs (-)-epigallocatechin gallate action as an anti-oxidant or a pro-oxidant for favorable activity. PMID:27221834

  1. Evaluation of phthalmustine, a new anticancer compound. The effect on Dalton's ascitic lymphoma in mice

    International Nuclear Information System (INIS)

    The anticancer property of phthalmustine, a hitherto unknown compounds containing N-mustard attached to the phthalimide ethyl chain was evaluated using a murine tumor model. The results indicate that the compound was effective in significantly restraining tumor growth. This was accompanied by marked improvement in host survival. No toxic reactions were apparent as reflected in skin and hair texture, body weight and behavioral pattern (food and water intake and activity). Blood picture showed a shift towards the normal following treatment. DNA synthesis in tumor cells was found to be affected as revealed by radioactive thymidine incorporation. (author)

  2. Anticancer effects of oligomeric proanthocyanidins on human colorectal cancer cell line, SNU-C4

    Institute of Scientific and Technical Information of China (English)

    Youn-Jung Kim; Hae-Jeong Park; Seo-Hyun Yoon; Mi-Ja Kim; Kang-Hyun Leem; Joo-Ho Chung; Hye-Kyung Kim

    2005-01-01

    AIM: Oligomeric proanthocyanidins (OPC), natural polyphenolic compounds found in plants, are known to have antioxidant and anti-cancer effects. We investigated whether the anti-cancer effects of the OPC are induced by apoptosis on human colorectal cancer cell line, SNU-C4.METHODS: Colorectal cancer cell line, SNU-C4 was cultured in RPMI 1640 medium supplemented with 10% fetal bovine serum. The cytotoxic effect of OPC was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenylt-etrazolium bromide (MTT) assay. To find out the apoptotic cell death, 4, 6-diamidino-2-phenylindole (DAPI) staining,terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay, reverse transcriptionpolymerase chain reaction (RT-PCR), and caspase-3 enzyme assay were performed.RESULTS: In this study, cytotoxic effect of OPC on SNUC4 cells appeared in a dose-dependent manner. OPC treatment (100 μg/mL) revealed typical morphological apoptotic features. Additionally OPC treatment (100 μg/mL)increased level of BAX and CASPASE-3, and decreased level of BCL-2 mRNA expression. Caspase-3 enzyme activity was also significantly increased by treatment of OPC (100 μg/mL) compared with control.CONCLUSION: These data indicate that OPC caused cell death by apoptosis through caspase pathways on human colorectal cancer cell line, SNU-C4.

  3. Molecular Biological Study of Anti-cancer Effects of Bee Venom Aqua-acupuncture

    Directory of Open Access Journals (Sweden)

    Park Chan-Yol

    2000-07-01

    Full Text Available To study anti-cancer effect and molecular biological mechanism of bee venom for aqua-acupuncture, the effects of bee venom on cell viability and apoptosis were analyzed using MTT assay, tryphan blue assay, [3H]thymidine release assay, flow cytometric analysis, and activity of caspase-3 protease activity assay. To explore whether anti-cancer effects of bee venom are associated with the transcriptional control of gene expression, quantitative RT-PCR analysis of apoptosis-related genes was performed. The obtained results are summarized as follows: 1. The MTT assay demonstrated that cell viability was decreased by bee venom in a dose-dependant manner. 2. Significant induction of apoptosis was identified using tryphan blue assay, [3H]thymidine release assay, and flow cytometric analysis of sub G1 fraction. 3. In analysis of caspase-3 protease activity, the activity had increased significantly, in a dose-dependant manner. 4. Quantitative RT-PCR analysis of the apoptosis-related genes showed that Bcl-2 and Bcl-XL were down-regulated whereas Bax was up-regulated by bee venom treatment.

  4. Low-intensity continuous ultrasound triggers effective bisphosphonate anticancer activity in breast cancer

    Science.gov (United States)

    Tardoski, Sophie; Ngo, Jacqueline; Gineyts, Evelyne; Roux, Jean-Paul; Clézardin, Philippe; Melodelima, David

    2015-11-01

    Ultrasound (US) is a non-ionizing pressure wave that can produce mechanical and thermal effects. Bisphosphonates have demonstrated clinical utility in bone metastases treatment. Preclinical studies suggest that bisphosphonates have anticancer activity. However, bisphosphonates exhibit a high affinity for bone mineral, which reduces their bioavailibity for tumor cells. Ultrasound has been shown to be effective for drug delivery but in interaction with gas bubbles or encapsulated drugs. We examined the effects of a clinically relevant dose of bisphosphonate zoledronate (ZOL) in combination with US. In a bone metastasis model, mice treated with ZOL+US had osteolytic lesions that were 58% smaller than those of ZOL-treated animals as well as a reduced skeletal tumor burden. In a model of primary tumors, ZOL+US treatment reduced by 42% the tumor volume, compared with ZOL-treated animals. Using a fluorescent bisphosphonate, we demonstrated that US forced the release of bisphosphonate from the bone surface, enabling a continuous impregnation of the bone marrow. Additionally, US forced the penetration of ZOL within tumors, as demonstrated by the intratumoral accumulation of unprenylated Rap1A, a surrogate marker of ZOL antitumor activity. Our findings made US a promising modality to trigger bisphosphonate anticancer activity in bone metastases and in primary tumors.

  5. The anticancer effect of chaetocin is enhanced by inhibition of autophagy.

    Science.gov (United States)

    Jung, H-J; Seo, I; Casciello, F; Jacquelin, S; Lane, S W; Suh, S-Il; Suh, M-H; Lee, J S; Baek, W-K

    2016-01-01

    Chaetocin is a fungal metabolite that possesses a potent antiproliferative activity in solid tumors by inducing cell death. Although recent studies have extended the role of chaetocin in tumors, the underlying molecular mechanisms such as the downstream cascade that induces cell death has not clearly been elucidated. In this study, we show that chaetocin is able to induce both apoptosis and autophagy in several hepatoma cell lines including HepG2, Hep3B and Huh7 cell lines. Moreover, we found that the inhibition of caspase-3/7 activity by z-VAD-fmk treatment was able to block chaetocin-mediated cell death, whereas blocking autophagy by Bafilomycin A1 or the knockdown of autophagy protein 5 enhanced cell death mediated by chaetocin. These findings suggest that chaetocin has a potent anticancer effect against hepatoma. Inhibition of autophagy may potentiate anticancer effects of chaetocin thus providing evidence that combined treatment with chaetocin and autophagy inhibitors will be an effective strategy for treating cancer. PMID:26890137

  6. Effect of Cellular Location of Human Carboxylesterase 2 on CPT-11 Hydrolysis and Anticancer Activity.

    Directory of Open Access Journals (Sweden)

    Yuan-Ting Hsieh

    Full Text Available CPT-11 is an anticancer prodrug that is clinically used for the treatment of metastatic colorectal cancer. Hydrolysis of CPT-11 by human carboxylesterase 2 (CE2 generates SN-38, a topoisomerase I inhibitor that is the active anti-tumor agent. Expression of CE2 in cancer cells is under investigation for the tumor-localized activation of CPT-11. CE2 is normally expressed in the endoplasmic reticulum of cells but can be engineered to direct expression of active enzyme on the plasma membrane or as a secreted form. Although previous studies have investigated different locations of CE2 expression in cancer cells, it remains unclear if CE2 cellular location affects CPT-11 anticancer activity. In the present study, we directly compared the influence of CE2 cellular location on substrate hydrolysis and CPT-11 cytotoxicity. We linked expression of CE2 and enhanced green fluorescence protein (eGFP via a foot-and-mouth disease virus 2A (F2A peptide to facilitate fluorescence-activated cell sorting to achieve similar expression levels of ER-located, secreted or membrane-anchored CE2. Soluble CE2 was detected in the medium of cells that expressed secreted and membrane-anchored CE2, but not in cells that expressed ER-retained CE2. Cancer cells that expressed all three forms of CE2 were more sensitive to CPT-11 as compared to unmodified cancer cells, but the membrane-anchored and ER-retained forms of CE2 were consistently more effective than secreted CE2. We conclude that expression of CE2 in the ER or on the membrane of cancer cells is suitable for enhancing CPT-11 anticancer activity.

  7. Approaches to improve the oral bioavailability and effects of novel anticancer drugs berberine and betulinic acid.

    Directory of Open Access Journals (Sweden)

    Chandraiah Godugu

    Full Text Available The poor bioavailability of Berberine (BBR and Betulinic acid (BA limits the development of these promising anticancer agents for clinical use. In the current study, BBR and BA in spray dried (SD mucoadhesive microparticle formulations were prepared.A patented dual channel spray gun technology established in our laboratory was used for both formulations. Gastrointestinal (GI permeability studies were carried out using Caco-2 cell monolayer grown in in-vitro system. The oral bioavailability and pharmacokinetic profile of SD formulations were studied in Sprague Dawley rats. A549 orthotopic and H1650 metastatic NSCLC models were utilized for the anticancer evaluations.Pharmacokinetic studies demonstrated that BBR and BA SD formulations resulted in 3.46 and 3.90 fold respectively, significant increase in plasma Cmax concentrations. AUC levels were increased by 6.98 and 7.41 fold in BBR and BA SD formulations, respectively. Compared to untreated controls groups, 49.8 & 53.4% decrease in the tumor volumes was observed in SD formulation groups of BBR and BA, respectively. Molecular studies done on excised tumor (A549 tissue suggested that BBR in SD form resulted in a significant decrease in the survivin, Bcl-2, cyclin D1, MMP-9, HIF-1α, VEGF and CD31 expressions. Cleaved caspase 3, p53 and TUNEL expressions were increased in SD formulations. The RT-PCR analysis on H1650 tumor tissue suggested that p38, Phospho-JNK, Bax, BAD, cleaved caspase 3&8 mRNA expressions were significantly increased in BA SD formulations. Chronic administration of BBR and BA SD formulations did not show any toxicity.Due to significant increase in oral bioavailability and superior anticancer effects, our results suggest that spray drying is a superior alternative formulation approach for oral delivery of BBR and BA.

  8. Ginseng Extract Enhances Anti-cancer Effect of Cytarabine on Human Acute Leukemia Cells

    Directory of Open Access Journals (Sweden)

    Yiju Hou

    2015-02-01

    Full Text Available Ginseng as a traditional medicine is well known to exhibit various pharmacological effects. Ginsenoside Rg3 is the active ingredient extracted from ginseng. The pharmacological modulatory effects of Rg3 on multidrug resistant cancer cells are reported in the present study. Cytarabine is a chemotherapeutic agent for the treatment of acute leukemia. However, this compound has serious side effects at high doses, for example hematopoiesis depression. In this study, using hl60 human leukemia cells, we investigated the possible synergistic anti-cancer effects between ginseng extract Rg3 and cytarabine on acute myeloid leukemia cells. Results of this study demonstrate that Rg3 can enhance the anti-proliferation effect of cytarabine on hl60 cells and may decrease the dosage of cytarabine needed for acute myeloid leukemia treatment.

  9. Effect of different extraction protocols on anticancer and antioxidant activities of Berberis koreana bark extracts.

    Science.gov (United States)

    Qadir, Syed Abdul; Kwon, Min Chul; Han, Jae Gun; Ha, Ji He; Chung, Hyang Suk; Ahn, Juhee; Lee, Hyeon Yong

    2009-03-01

    High-pressure extraction and ultrasonification extraction techniques were employed to extract bioactive compounds from Berberis koreana. This study aimed to determine the effect of ultrasonification in a high pressure process on the extraction yield, and the anticancer and antioxidant activities of the B. koreana bark extract. The effect of high-pressure extraction time when carried out for 5 and 15 min (HP5 and HP15) was also investigated. The best extraction yield with maximum percentage of phenolic compounds was obtained using high pressure with sonification (HPWS) extraction method. Experimental results indicated that HPWS altered the antioxidant activities, including the scavenging capacity of diphenylpicrylhydrazyl (DPPH) and xanthine oxidase. HP5 and HP15 with conventional extraction have almost similar bioactivity, but showed lower antioxidant and anticancer activities compared to HPWS. The results showed that the application of ultrasonification improved the extraction efficiency for bioactive compounds and, as deduced from chromatographic profiles, it may have allowed the release of new compounds. The scanning electron microscope (SEM) showed evidence of rupturing of the tissue surface treated with HPWS, in contrast to conventional extraction, HP5, and HP15. The HPWS extraction was not only more efficient but also convenient for the recovery and purification of the active compounds of hard plant tissues. PMID:19269602

  10. Synthesis and investigation of the anticancer effects of estrone-16-oxime ethers in vitro.

    Science.gov (United States)

    Berényi, Ágnes; Minorics, Renáta; Iványi, Zoltán; Ocsovszki, Imre; Ducza, Eszter; Thole, Hubert; Messinger, Josef; Wölfling, János; Mótyán, Gergő; Mernyák, Erzsébet; Frank, Éva; Schneider, Gyula; Zupkó, István

    2013-01-01

    An expanding body of evidence indicates the possible role of estrane derivatives as useful anticancer agents. The aim of this study was to describe the cytotoxic effects of 63 newly synthetized estrone-16-oxime ethers on human cancer cell lines (cervix carcinoma HeLa, breast carcinoma MCF7 and skin epidermoid carcinoma A431), studied by means of the MTT assay. Four of the most promising compounds were selected for participation in additional experiments in order to characterize the mechanism of action, including cell cycle analysis, morphological study and the 5-bromo-2'-deoxyuridine incorporation assay. The cancer selectivity was tested on a noncancerous fibroblast cell line (MRC-5). Since apoptosis and cell cycle disturbance were observed, caspase-3 activities were further assayed for the two most effective agents. These estrone-16-oxime analogs activated caspase-3 and changed the mRNA level expression of endogenous factors regulating the G1-S phase transition (retinoblastoma protein, CDK4 and p16). The repression of retinoblastoma protein was reinforced at a protein level too. These experimental data lead to the conclusion that estrone-16-oxime ethers may be regarded as potential starting structures for the design of novel anticancer agents. PMID:23127813

  11. Garcinol: Current status of its anti-oxidative, anti-inflammatory and anti-cancer effects.

    Science.gov (United States)

    Liu, Chaoqun; Ho, Paul Chi-Lui; Wong, Fang Cheng; Sethi, Gautam; Wang, Ling Zhi; Goh, Boon Cher

    2015-06-28

    Garcinol is the main medicinal component of the dried fruit rind of Garcinia indica (G. indica), which has traditionally been extensively used to treat gastric ailments and skin irritation. In vitro studies of garcinol revealed its potential therapeutic effects, such as its anti-oxidative, anti-inflammatory and anti-cancer properties. Similarly, in vivo studies in animal models also demonstrated the efficacy of garcinol for the treatment of various inflammatory and cancerous conditions. Despite being well tolerated in preclinical studies, the toxicological profile of garcinol remains elusive. More importantly, systematic pharmacokinetics (PK) studies of garcinol to establish an appropriate route of administration and its effective concentration range under physiological conditions have not yet been performed. PK studies play an essential role in translating the preclinical findings of garcinol from cell line models and animal species to humans, thereby facilitating dose selection, the characterization of the therapeutic index, identification of a metabolic pathway, and the determination of garcinol's potency and tolerability. This paper reviews the current studies of garcinol as a potential anti-oxidant, anti-inflammatory and anti-cancer agent and highlights the importance of performing preclinical PK and toxicological studies on garcinol for its development pipeline. PMID:25796441

  12. Curcumin and its promise as an anticancer drug: An analysis of its anticancer and antifungal effects in cancer and associated complications from invasive fungal infections.

    Science.gov (United States)

    Chen, Jin; He, Zheng-Min; Wang, Feng-Ling; Zhang, Zheng-Sheng; Liu, Xiu-zhen; Zhai, Dan-Dan; Chen, Wei-Dong

    2016-02-01

    Invasive fungal infections (IFI) are important complications of cancer, and they have become a major cause of morbidity and mortality in cancer patients. Effective anti-infection therapy is necessary to inhibit significant deterioration from these infections. However, they are difficult to treat, and increasing antifungal drug resistance often leads to a relapse. Curcumin, a natural component that is isolated from the rhizome of Curcuma longa plants, has attracted great interest among many scientists studying solid cancers over the last half century. Interestingly, curcumin provides an ideal alternative to current therapies because of its relatively safe profile, even at high doses. To date, curcumin's potent antifungal activity against different strains of Candida, Cryptococcus, Aspergillus, Trichosporon and Paracoccidioides have been reported, indicating that curcumin anticancer drugs may also possess an antifungal role, helping cancer patients to resist IFI complications. The aim of this review is to discuss curcumin's dual pharmacological activities regarding its applications as a natural anticancer and antifungal agent. These dual pharmacological activities are expected to lead to clinical trials and to improve infection survival among cancer patients. PMID:26723514

  13. Hepatoprotective, Antioxidant, and Anticancer Effects of the Tragopogon porrifolius Methanolic Extract

    Directory of Open Access Journals (Sweden)

    Clara Tenkerian

    2015-01-01

    Full Text Available Tragopogon porrifolius (Asteraceae, commonly referred to as white salsify, is an edible herb used in Lebanese folk medicine to treat cancer and liver dysfunction. In this study, we investigated the antioxidant activity of Tragopogon porrifolius methanolic extract, both in vitro and in vivo, in addition to its hepatoprotective and anticancer activities. Total phenolic and flavonoid contents were measured and found to be 37.0±1.40 mg GAE/g and 16.6±0.42 mg QE/g dry weight, respectively. In vitro antioxidant assays revealed an FRAP value of 659±13.8 µmol Fe2+/g of extract and DPPH IC50 value 15.2 µg/mL. In rats subjected to CCl4-induced hepatotoxicity, significant increase in CAT, SOD, and GST levels was detected. The highest dose of the extract (250 mg/kg recorded a fold increase of 1.68 for SOD, 2.49 for GST, and 3.2 for CAT. The extract also showed substantial decrease in AST (57%, ALT (56%, and LDH (65% levels. Additionally, the extract caused a dose-dependent decrease in cell viability and proliferation. In conclusion, the methanolic extract of T. porrifolius displayed a relatively high antioxidant activity both in vitro and in vivo as well as hepatoprotective potential against liver toxicity in rats and anticancer effect on MDA-MB-231 and Caco-2 cells.

  14. Hepatoprotective, Antioxidant, and Anticancer Effects of the Tragopogon porrifolius Methanolic Extract.

    Science.gov (United States)

    Tenkerian, Clara; El-Sibai, Mirvat; Daher, Costantine F; Mroueh, Mohamad

    2015-01-01

    Tragopogon porrifolius (Asteraceae), commonly referred to as white salsify, is an edible herb used in Lebanese folk medicine to treat cancer and liver dysfunction. In this study, we investigated the antioxidant activity of Tragopogon porrifolius methanolic extract, both in vitro and in vivo, in addition to its hepatoprotective and anticancer activities. Total phenolic and flavonoid contents were measured and found to be 37.0 ± 1.40 mg GAE/g and 16.6 ± 0.42 mg QE/g dry weight, respectively. In vitro antioxidant assays revealed an FRAP value of 659 ± 13.8 µmol Fe(2+)/g of extract and DPPH IC50 value 15.2 µg/mL. In rats subjected to CCl4-induced hepatotoxicity, significant increase in CAT, SOD, and GST levels was detected. The highest dose of the extract (250 mg/kg) recorded a fold increase of 1.68 for SOD, 2.49 for GST, and 3.2 for CAT. The extract also showed substantial decrease in AST (57%), ALT (56%), and LDH (65%) levels. Additionally, the extract caused a dose-dependent decrease in cell viability and proliferation. In conclusion, the methanolic extract of T. porrifolius displayed a relatively high antioxidant activity both in vitro and in vivo as well as hepatoprotective potential against liver toxicity in rats and anticancer effect on MDA-MB-231 and Caco-2 cells. PMID:25694787

  15. Anti-Cancer Effect of Angelica Sinensis on Women’s Reproductive Cancer

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    Hong-Hong Zhu

    2012-06-01

    Full Text Available Objective: Danggui, the root of Angelica Sinensis, has traditionally been used for the treatment of women’s reproductive disorders in China for thousands of years. This study was to determine whether Danggui have potential anti-cancer effect on women’s cancer and its potential mechanism. Methods: Danggui was extracted by ethanol. The Cell Titer 96® Aqueous Non-Radioactive Cell Proliferation Assay was used to compare the effects of Danggui on human breast (MCF-7 and 7368 and cervical (CaSki and SiHa cancer cells with its effects on normal fibroblasts (HTB-125. A revised Ames test was used to test for antimutagenicity. The standard strains of Salmonella typhimarium (TA 100 and 102 were used in the test. Methyl methane sulfonate (MMS and UV light were used as positive mutagen controls and ethanol and double distilled water (DDW as controls. The SAS statistical software was used to analyze the data. Results: Danggui was found to be much more toxic to all cancer cell lines tested than to normal fibroblasts. There was a significant negative dose-effect relationship between Danggui and cancer cell viability. Average viability of MCF-7 was 69.5%, 18.4%, 5.7%, 5.7%, and 5.0% of control for Danggui doses 0.07, 0.14, 0.21, 0.32, and 0.64 ug/ul, respectively, with a Ptrend < 0.0001. Half maximal inhibitory dose (ID50 of Danggui for cancer cell lines MCF-7, CaSki, SiHa and CRL-7368 was 0.10, 0.09, 0.10 and 0.07 ug/ul, Functional Foods in Health and Disease 2012, 2(6:242-250respectively. For the normal fibroblasts, ID50 was 0.58 ug/ul. At a dose of 0.32 ug/ul, Danggui killed over 90% of the cells in each cancer cell line, but at the same dose, only 12.3 % of the normal HTB-125 cells were killed. Revertants per plate of TA 100 decreased with the introduction of increasing doses of Danggui extracts with a Ptrend < 0.0001 when UV light was used as a mutagen. There was no difference in revertants per plate between ethanol and DDW control groups. Conclusions

  16. Age-related dynamics of constitutive cytokine transcription levels of feline monocytes.

    Science.gov (United States)

    Kipar, A; Baptiste, K; Meli, M L; Barth, A; Knietsch, M; Reinacher, M; Lutz, H

    2005-03-01

    Monocytes/macrophages are central mediators of inflammation and immunity and therefore of major interest in the study of immunosenescence. In healthy adult cats, monocytes have been shown to constitutively transcribe pro- and anti-inflammatory cytokines. However, in order to characterize the effect of age, feline monocyte functions were examined for changes in cytokine transcription levels in early stages of immunosenescence. For this purpose, isolated, short-term cultured monocytes from barrier-maintained adult cats of different ages (15 mo to 10 yr) were examined for transcription of IL-1 beta, IL-6, IL-10, IL-12 p40 and TNF-alpha by real-time PCR. Transcription levels of cytokines varied and were generally highest for IL-1 beta. For IL-1 beta, IL-6 and IL-12 p40, both young and old cats exhibited highest levels. The age association was significant. TNF-alpha appeared to be transcribed at similar levels over the examination period, whereas IL-10 tended to decline with age but without any statistical significant differences. The observed age association of the constitutive transcription of some cytokines indicates a drop in monocyte activities from youth to middle age, which is then followed by a (progressive) increase with increasing age. This provides evidence that monocytes are in part responsible for the pro-inflammatory status observed with ageing. PMID:15763402

  17. Chloroquine potentiates the anti-cancer effect of 5-fluorouracil on colon cancer cells

    International Nuclear Information System (INIS)

    Chloroquine (CQ), the worldwide used anti-malarial drug, has recently being focused as a potential anti-cancer agent as well as a chemosensitizer when used in combination with anti-cancer drugs. It has been shown to inhibit cell growth and/or to induce cell death in various types of cancer. 5-Fluorouracil (5-FU) is the chemotherapeutic agent of first choice in colorectal cancer, but in most cases, resistance to 5-FU develops through various mechanisms. Here, we focused on the combination of CQ as a mechanism to potentiate the inhibitory effect of 5-FU on human colon cancer cells. HT-29 cells were treated with CQ and/or 5-FU, and their proliferative ability, apoptosis and autophagy induction effects, and the affection of the cell cycle were evaluated. The proliferative ability of HT-29 was analyzed by the MTS assay. Apoptosis was quantified by flow-cytometry after double-staining of the cells with AnnexinV/PI. The cell cycle was evaluated by flow-cytometry after staining of cells with PI. Autophagy was quantified by flow-cytometry and Western blot analysis. Finally, to evaluate the fate of the cells treated with CQ and/or 5-FU, the colony formation assay was performed. 5-FU inhibited the proliferative activity of HT-29 cells, which was mostly dependent on the arrest of the cells to the G0/G1-phase but also partially on apoptosis induction, and the effect was potentiated by CQ pre-treatment. The potentiation of the inhibitory effect of 5-FU by CQ was dependent on the increase of p21Cip1 and p27Kip1 and the decrease of CDK2. Since CQ is reported to inhibit autophagy, the catabolic process necessary for cell survival under conditions of cell starvation or stress, which is induced by cancer cells as a protective mechanism against chemotherapeutic agents, we also analyzed the induction of autophagy in HT-29. HT-29 induced autophagy in response to 5-FU, and CQ inhibited this induction, a possible mechanism of the potentiation of the anti-cancer effect of 5-FU. Our

  18. Mechanistic study of the anti-cancer effect of Gynostemma pentaphyllum saponins in the Apc(Min/+) mouse model.

    Science.gov (United States)

    Tai, William Chi-Shing; Wong, Wing-Yan; Lee, Magnolia Muk-Lan; Chan, Brandon Dow; Lu, Cheng; Hsiao, Wen-Luan Wendy

    2016-05-01

    Gynostemma pentaphyllum saponins (GpS) have been shown to have anti-cancer activity. However, the underlying mechanisms remain unclear. In this study, we used the Apc(Min) (/+) colorectal cancer (CRC) mouse model to investigate the anti-cancer effect of GpS and we demonstrated that GpS treatment could significantly reduce the number and size of intestinal polyps in Apc(Min) (/+) mice. In order to identify the potential targets and mechanisms involved, a comparative proteomics analysis was performed and 40 differentially expressed proteins after GpS treatment were identified. Bioinformatics analyses suggested a majority of these proteins were involved in processes related to cellular redox homeostasis, and predicted Raf-1 as a potential target of GpS. The upregulation of two proteins known to be involved in redox homeostasis, peroxiredoxin-1 (Prdx1) and peroxiredoxin-2 (Prdx2), and the downregulation of Raf-1 were validated using Western blot analysis. After further investigation of the associated signaling networks, we postulated that the anti-cancer effect of GpS was mediated through the upregulation of Prdx1 and Prdx2, suppression of Ras, RAF/MEK/ERK/STAT, PI3K/AKT/mTOR signaling and modulation of JNK/p38 MAPK signaling. We also examined the potential combinatorial effect of GpS with the chemotherapeutic 5-fluorouracil (5-FU) and found that GpS could enhance the anti-cancer efficacy of 5-FU, further suppressing the number of polyps in Apc(Min/+) mice. Our findings highlight the potential of GpS as an anti-cancer agent, the potential mechanisms of its anti-cancer activities, and its effect as an adjuvant of 5-FU in the chemotherapy of CRC. PMID:26970558

  19. Curcumin, a dietary component, has anticancer, chemosensitization, and radiosensitization effects by down-regulating the MDM2 oncogene through the PI3K/mTOR/ETS2 pathway.

    Science.gov (United States)

    Li, Mao; Zhang, Zhuo; Hill, Donald L; Wang, Hui; Zhang, Ruiwen

    2007-03-01

    The oncoprotein MDM2, a major ubiquitin E3 ligase of tumor suppressor p53, has been suggested as a novel target for human cancer therapy based on its p53-dependent and p53-independent activities. We have identified curcumin, which has previously been shown to have anticancer activity, as an inhibitor of MDM2 expression. Curcumin down-regulates MDM2, independent of p53. In a human prostate cancer cell lines PC3 (p53(null)), curcumin reduced MDM2 protein and mRNA in a dose- and time-dependent manner, and enhanced the expression of the tumor suppressor p21(Waf1/CIP1). The inhibitory effects occur at the transcriptional level and seem to involve the phosphatidylinositol 3-kinase/mammalian target of rapamycin/erythroblastosis virus transcription factor 2 pathway. Curcumin induced apoptosis and inhibited proliferation of PC3 cells in culture, but both MDM2 overexpression and knockdown reduced these effects. Curcumin also inhibited the growth of these cells and enhanced the cytotoxic effects of gemcitabine. When it was administered to tumor-bearing nude mice, curcumin inhibited growth of PC3 xenografts and enhanced the antitumor effects of gemcitabine and radiation. In these tumors, curcumin reduced the expression of MDM2. Down-regulation of the MDM2 oncogene by curcumin is a novel mechanism of action that may be essential for its chemopreventive and chemotherapeutic effects. Our observations help to elucidate the process by which mitogens up-regulate MDM2, independent of p53, and identify a mechanism by which curcumin functions as an anticancer agent. PMID:17332326

  20. Radiation effect studies on anticancer drugs, cyclophosphamide and doxorubicin for radiation sterilization

    Energy Technology Data Exchange (ETDEWEB)

    Varshney, L. E-mail: lalitv@magnum.barc.ernet.in; Dodke, P.B

    2004-12-01

    Two anticancer drugs, cyclophosphamide (CPH) and doxorubicin hydrochloride (DOXO), in powder form were exposed to a range of doses of {sup 60}Co gamma and electron beam radiation to study the effects of ionizing radiation. Pharmacopoeia tests, discolouration, degradation products, effect of irradiation temperature and dose rate were investigated. CPH undergoes less than 2% degradation at 30 kGy. Chromatographic studies revealed formation of several trace level degradation products, discolouration and free radicals in the irradiated CPH. N,N-bis (2-chloroethyl) group in the molecule is particularly sensitive to radiation degradation. Irradiation to 5 kGy at low temperature (77 K) did not result in significant changes. DOXO was observed to be quite radiation resistant and did not undergo significant changes in its physico-chemical properties and degradation product profile. It can be radiation sterilized at normal sterilization dose of 25 kGy.

  1. Radiation effect studies on anticancer drugs, cyclophosphamide and doxorubicin for radiation sterilization

    International Nuclear Information System (INIS)

    Two anticancer drugs, cyclophosphamide (CPH) and doxorubicin hydrochloride (DOXO), in powder form were exposed to a range of doses of 60Co gamma and electron beam radiation to study the effects of ionizing radiation. Pharmacopoeia tests, discolouration, degradation products, effect of irradiation temperature and dose rate were investigated. CPH undergoes less than 2% degradation at 30 kGy. Chromatographic studies revealed formation of several trace level degradation products, discolouration and free radicals in the irradiated CPH. N,N-bis (2-chloroethyl) group in the molecule is particularly sensitive to radiation degradation. Irradiation to 5 kGy at low temperature (77 K) did not result in significant changes. DOXO was observed to be quite radiation resistant and did not undergo significant changes in its physico-chemical properties and degradation product profile. It can be radiation sterilized at normal sterilization dose of 25 kGy

  2. BCc1, the novel antineoplastic nanocomplex, showed potent anticancer effects in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Kalanaky S

    2015-12-01

    Full Text Available Somayeh Kalanaky,1,2 Maryam Hafizi,1–3 Saideh Fakharzadeh,1 Mohammad Vasei,4 Ladan Langroudi,5 Ehsan Janzamin,6 Seyed Mahmoud Hashemi,7 Maryam Khayamzadeh,2 Masoud Soleimani,6 Mohammad Esmaeil Akbari,2 Mohammad Hassan Nazaran1 1Department of Research and Development, Sodour Ahrar Shargh Company, Tehran, Iran; 2Cancer Research Centre, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 3Stem Cell Technology Research Center, Tehran, Iran; 4Department of Pathology, Tehran University of Medical Sciences, Tehran, Iran; 5Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; 6Department of Haematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; 7Department of Immunology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Purpose: In spite of all the efforts and researches on anticancer therapeutics, an absolute treatment is still a myth. Therefore, it is necessary to utilize novel technologies in order to synthesize smart multifunctional structures. In this study, for the first time, we have evaluated the anticancer effects of BCc1 nanocomplex by vitro and in vivo studies, which is designed based on the novel nanochelating technology.Methods: Human breast adenocarcinoma cell line (MCF-7 and mouse embryonic fibroblasts were used for the in vitro study. Antioxidant potential, cell toxicity, apoptosis induction, and CD44 and CD24 protein expression were evaluated after treatment of cells with different concentrations of BCc1 nanocomplex. For the in vivo study, mammary tumor-bearing female Balb/c mice were treated with different doses of BCc1 and their effects on tumor growth rate and survival were evaluated.Results: BCc1 decreased CD44 protein expression and increased CD24 protein expression. It induced MCF-7 cell apoptosis but at the same concentrations did not have negative effects on mouse embryonic fibroblasts viability and protected

  3. Mechanistic study of the anticancer effect of Gynostemma pentaphyllum saponins in R6 fibroblast cell

    Institute of Scientific and Technical Information of China (English)

    MoZ; HsaiW

    2002-01-01

    The anticancer effect of Gynostemma pentaphyllum (Gp)saponins was tested.The results indicated that the Gp saponins inhibited ras-induced foci in dosage and time-dependent manners.To facilitate the investigation of the mode of inhibition of Gp in living cells,a green fluorescent protein-ras fusion construct was generated and used to substitute ras in the study.Cells acquired GFP-ras gene grew into green fluorescent foci with striking transforming morphology in the absence of Gp,whereas the GFP-ras transfected cell,in most of cases,remained as single green fluorescent cell with Gp saponins present in the medium.Gp saponins exhibited non-cytotoxic effect on either normal or the transformed R6 cells.However.Gp saponins posted a strong inhibition against the growth of the rastransformed cells that were co-cultivated with normal R6 cells.The level of Raf-1 protein was sharply down-regulated after Gp treatment.Gp treatment can also induce instability of Raf-1,instead of transcriptional inactivation of the protein expression.A cDNA microarray analysis displayed four genes,i.e.β2-microglobulin,GST7-7,gelatinase A and cathepsin L were up-regulated,while three genes:Erk-1,γIGFBP-6,and 14-3-3 zeta were down-regulated upon treatment with Gp saponins.The results were verified by Northern blot analysis.The finding that an anti-cancer effect of a non-toxic drug may be mediated through the surrounding normal cells is conceptually novel and should have a broad implication in the future development of drugs or dietary supplements with cancer prevention function.

  4. A Possible Anticancer Agent, Type III Interferon, Activates Cell Death Pathways and Produces Antitumor Effects

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    Masatoshi Tagawa

    2011-01-01

    Full Text Available Recently identified interleukin-28 and -29 belong to a novel type III interferon (IFN family, which could have distinct biological properties from type I and II IFNs. Type I IFNs, IFN-α/β, have been clinically applied for treating a certain kind of malignancies for over 30 years, but a wide range of the adverse effects hampered the further clinical applications. Type III IFNs, IFN-λs, have similar signaling pathways as IFN-α/β and inhibits proliferation of tumor cells through cell cycle arrest or apoptosis. Restricted patterns of type III IFN receptor expression in contrast to ubiquitously expressed IFN-α/β receptors suggest that type III IFNs have limited cytotoxicity to normal cells and can be a possible anticancer agent. In this paper, we summarize the current knowledge on the IFN-λs-mediated tumor cell death and discuss the functional difference between type I and III IFNs.

  5. Anticancer Effects of Extracts from the Fruit of Morinda Citrifolia (Noni) in Breast Cancer Cell Lines.

    Science.gov (United States)

    Sharma, K; Pachauri, S D; Khandelwal, K; Ahmad, H; Arya, A; Biala, P; Agrawal, S; Pandey, R R; Srivastava, A; Srivastav, A; Saxena, J K; Dwivedi, A K

    2016-03-01

    Morinda citrifolia L. (NONI) fruits have been used for thousands of years for the treatment of many health problems including cancer, cold, diabetes, flu, hypertension, and pain. Plant extracts have reported several therapeutic benefits, but extraction of individual compound from the extract often exhibits limited clinical utility as the synergistic effect of various natural ingredients gets lost. They generally constitute polyphenols and flavonoids. Studies have suggested that these phytochemicals, especially polyphenols, display high antioxidant properties, which help to reduce the risk of degenerative diseases, such as cancer and cardiovascular diseases. Several in-vitro and in-vivo studies have shown that Noni fruits have antioxidant, anti-inflammatory, anti-dementia, liver-protective, anticancer, analgesic, and immunomodulatory effects. Till date about 7 in vitro cancer studies have been done, but a detailed in vitro study including cell cycle and caspase activation assay on breast cancer cell line has not been done. In the present study different Noni fruit fractions have tested on cancer cell lines MCF-7, MDA-MB-231 (breast adenocarcinoma) and one non-cancer cell line HEK-293 (Human embryonic kidney). Out of which ethylacetate extract showed a higher order of in vitro anticancer activity profile. The ethylacetate extract strongly inhibited the proliferation of MCF-7, MDA-MB-231 and HEK-293 cell lines with IC50 values of 25, 35, 60 µg/ml respectively. The extract showed increase in apoptotic cells in MCF-7 and MDA-MB-231 cells and arrested the cell cycle in the G1/S phase in MCF-7 and G0/G1 phase in MDA-MB-231 cells. Noni extract also decreases the intracellular ROS generation and mitochondrial membrane potential. PMID:26158795

  6. Anticancer Effects of the Nitric Oxide-Modified Saquinavir Derivative Saquinavir-NO against Multidrug-Resistant Cancer Cells

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    Florian Rothweiler

    2010-12-01

    Full Text Available The human immunodeficiency virus (HIV protease inhibitor saquinavir shows anticancer activity. Although its nitric oxide-modified derivative saquinavir-NO (saq-NO was less toxic to normal cells, it exerted stronger inhibition of B16 melanoma growth in syngeneic C57BL/6 mice than saquinavir did. Saq-NO has been shown to block proliferation, upregulate p53 expression, and promote differentiation of C6 glioma and B16 cells. The anticancer activity of substances is frequently hampered by cancer cell chemoresistance mechanisms. Therefore, we here investigated the roles of p53 and the ATP-binding cassette (ABC transporters P-glycoprotein (P-gp, multidrug resistance-associated protein 1 (MRP1, and breast cancer resistance protein 1 (BCRP1 in cancer cell sensitivity to saq-NO to get more information about the potential of saq-NO as anticancer drug. Saq-NO exerted anticancer effects in lower concentrations than saquinavir in a panel of human cancer cell lines. Neither p53 mutation or depletion nor expression of P-gp, MRP1, or BCRP1 affected anticancer activity of saq-NO or saquinavir. Moreover, saq-NO sensitized P-gp-, MRP1-, or BCRP1-expressing cancer cells to chemotherapy. Saq-NO induced enhanced sensitization of P-gp- or MRP1-expressing cancer cells to chemotherapy compared with saquinavir, whereas both substances similarly sensitized BCRP1-expressing cells. Washout kinetics and ABC transporter ATPase activities demonstrated that saq-NO is a substrate of P-gp as well as of MRP1. These data support the further investigation of saq-NO as an anticancer drug, especially in multidrug-resistant tumors.

  7. Acetaldehyde-induced cytotoxicity involves induction of spermine oxidase at the transcriptional level.

    Science.gov (United States)

    Uemura, Takeshi; Tanaka, Yuka; Higashi, Kyohei; Miyamori, Daisuke; Takasaka, Tomokazu; Nagano, Tatsuo; Toida, Toshihiko; Yoshimoto, Kanji; Igarashi, Kazuei; Ikegaya, Hiroshi

    2013-08-01

    Ethanol consumption causes serious liver injury including cirrhosis and hepatocellular carcinoma. Ethanol is metabolized mainly in the liver to acetic acid through acetaldehyde. We investigated the effect of ethanol and acetaldehyde on polyamine metabolism since polyamines are essential factors for normal cellular functions. We found that acetaldehyde induced spermine oxidase (SMO) at the transcriptional level in HepG2 cells. The levels and activities of ornithine decarboxylase (ODC) and spermidine/spermine acetyltransferase (SSAT) were not affected by acetaldehyde. Spermidine content was increased and spermine content was decreased by acetaldehyde treatment. Knockdown of SMO expression using siRNA reduced acetaldehyde toxicity. Acetaldehyde exposure increased free acrolein levels. An increase of acrolein by acetaldehyde was SMO dependent. Our results indicate that cytotoxicity of acetaldehyde involves, at least in part, oxidation of spermine to spermidine by SMO, which is induced by acetaldehyde. PMID:23707493

  8. Effect of methionine and glucosamine conjugation on the anticancer activity of aromatic dinitrobenzamide mustards

    Indian Academy of Sciences (India)

    Karmakar Subhendu; Sudipta Bhattacharyya; Arindam Mukherjee

    2016-03-01

    Certain nutrients viz.,glucose and methionine are consumed more by cancer cells. Hence, an anticancer agent conjugated to them may render more toxicity in cancer cells due to higher uptake. To probe this effect, methionine and glucosamine were conjugated to a series of well-known aromatic dinitrobenzamide mustards. The in vitro cytotoxicity studies performed to probe the effect of such conjugation showed that the conjugation of methionine and glucosamine to one of the dinitrobenzamide mustard led to more toxicity selectively in human breast adenocarcinoma (MCF-7) cell lines. However, effect of functionalization cannot be generalized. Hypoxia based studies showed that IC50 value did not show much change from normoxic condition which is encouraging as many drugs deactivate in hypoxia. Among the glucosamine and methionine conjugated dinitrobenzamide mustards, the methionine conjugated aromatic dinitrobenzamide mustard of 2-chlorobenzoic acid is the most effective one. It acts by inducing apoptosis through G2/M phase arrest and encouragingly, is much less toxic to nontumorigenic human embryonic kidney (HEK-293T) and mouse embryonic fibroblast (NIH 3T3) cell lines in vitro.

  9. Pharmacokinetic Interaction of Rifampicin with Oral Versus Intravenous Anticancer Drugs: Challenges, Dilemmas and Paradoxical Effects Due to Multiple Mechanisms.

    Science.gov (United States)

    Srinivas, Nuggehally R

    2016-06-01

    Since many drugs are cytochrome P450 (CYP)-3A4 substrates, it has become common practice to assess drug-drug interaction (DDI) potential with a CYP3A4 inhibitor (ketoconazole) or inducer (rifampicin) in early drug development. Such an evaluation is relevant to anticancer drugs with metabolism governed by CYP3A4. DDIs with rifampicin are complex, involving other physiological mechanisms that may impact overall pharmacokinetics. Our objective was to study and delineate such mechanisms for oral versus intravenous anticancer drugs. We hypothesized that DDIs between anticancer drugs and rifampicin were primarily driven by CYP3A4 induction. This hypothesis was proven for the oral anticancer drugs; however, in some cases, other intrinsic mechanisms such as P-glycoprotein (Pgp)/UDP glucuronosyl transferase (UGT) induction and transporter inhibition may have played an important role alongside the induced CYP3A4 enzymes. The hypothesis that CYP3A4 induction would decrease drug exposure appeared paradoxical for intravenous romidepsin and-to a somewhat lesser extent-for cabazitaxel. In light of this dilemma in the interpretation of the pharmacokinetic data with rifampicin, several questions require further consideration. Given the complexity and paradoxical effects arising with DDIs with rifampicin, the continued preference for rifampicin as CYP3A4 inducer needs immediate re-appraisal. PMID:27098526

  10. Fucoxanthin: A Marine Carotenoid Exerting Anti-Cancer Effects by Affecting Multiple Mechanisms

    Directory of Open Access Journals (Sweden)

    Sangeetha Ravi Kumar

    2013-12-01

    Full Text Available Fucoxanthin is a marine carotenoid exhibiting several health benefits. The anti-cancer effect of fucoxanthin and its deacetylated metabolite, fucoxanthinol, is well documented. In view of its potent anti-carcinogenic activity, the need to understand the underlying mechanisms has gained prominence. Towards achieving this goal, several researchers have carried out studies in various cell lines and in vivo and have deciphered that fucoxanthin exerts its anti-proliferative and cancer preventing influence via different molecules and pathways including the Bcl-2 proteins, MAPK, NFκB, Caspases, GADD45, and several other molecules that are involved in either cell cycle arrest, apoptosis, or metastasis. Thus, in addition to decreasing the frequency of occurrence and growth of tumours, fucoxanthin has a cytotoxic effect on cancer cells. Some studies show that this effect is selective, i.e., fucoxanthin has the capability to target cancer cells only, leaving normal physiological cells unaffected/less affected. Hence, fucoxanthin and its metabolites show great promise as chemotherapeutic agents in cancer.

  11. The Study on Acute and Subacute Toxicity and Sarcoma-180 Anti-cancer Effects of Vermilionum

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    Ki-Rok Kwon

    2003-12-01

    Full Text Available Background & Methods : In order to measure the acute and subacute toxicity of Vermilionum and it's anti-cancer effects, Sarcoma-180 abdominal cancer cells were injected intravenously. The following results were obtained after measuring the survival rate, toxicity of the NK cells, and IL-2 productivity. Results : 1. It was impossible to measure LD50 value in the acute toxicity test and no toxic effects were witnessed in the clinical observation. 2. No significant differences were shown in the weight changes between the experiment groups and the control group in the acute toxicity test. 3. No peculiar toxic effects were shown in the subacute toxicity test and the weight changes were insignificant between the experiment groups and the control group. 4. In measuring the survival rate after inducing abdominal cancer by Sarcoma-180, the experiment groups showed increased of 9,52% compared to the control group. 5. In measuring the activity of NK cells, no significant changes were shown between the experiment groups and the control group. 6. In measuring the productivity of IL-2, significant reduction was shown in the experiment groups compared to the normal group, but no significance was witnessed compared to the control group.

  12. Transcript levels of major interleukins in relation to the clinicopathological profile of patients with tuberculous intervertebral discs and healthy controls.

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    Chong Liu

    Full Text Available The purpose of the present study was to simultaneously examine the transcript levels of a large number of interleukins (ILs; IL-9, IL-10, IL-12, IL-13, IL-16, IL-17, IL-18, IL-26, and IL-27 and investigate their correlation with the clinicopathological profiles of patients with tuberculous intervertebral discs.Clinical data were collected from 150 patients participating in the study from January 2013 to December 2013. mRNA expression levels in 70 tuberculous, 70 herniated, and 10 control intervertebral disc specimens were determined by real-time polymerase chain reaction.IL-10, IL-16, IL-17, IL-18, and IL-27 displayed stronger expression in tuberculous spinal disc tissue than in normal intervertebral disc tissue (P<0.05. Our results illustrated multiple correlations among IL-10, IL-16, IL-17, IL-18, and IL-27 mRNA expression in tuberculous samples. Smoking habits were found to have a positive correlation with IL-17 transcript levels and a negative correlation with IL-10 transcript levels (P<0.05. Pain intensity, symptom duration, C-reactive protein levels, and the erythrocyte sedimentation rate exhibited multiple correlations with the transcript levels of several ILs (P<0.05.The experimental data imply a double-sided effect on the activity of ILs in tuberculous spinal intervertebral discs, suggesting that they may be involved in intervertebral discs destruction. Our findings also suggest that smoking may affect the intervertebral discs destruction process of spinal tuberculosis. However, further studies are necessary to elucidate the exact role of ILs in the intervertebral discs destruction process of spinal tuberculosis.

  13. Assessment of Performance of Manufacturing Procedures in a Unit for Production of Investigational Anticancer Agents, Using a Mixed Effects Analysis

    OpenAIRE

    van der Schoot, S. C.; Nuijen, B; Huitema, A D R; Beijnen, J.H.

    2007-01-01

    Purpose To identify the magnitude and sources of variability of a generic, aseptic manufacturing process for experimental anticancer agents employed at our facility, and to estimate the effects on product quality. Materials and Methods In-process and quality control data of all products manufactured according to this generic process (composed of weighing, dissolution, filtration, filling, semi-stoppering and lyophilization) over a 3-year period were retrospectively analyzed using mixed-effect...

  14. Anticancer Effect of Fucoidan in Combination with Tyrosine Kinase Inhibitor Lapatinib

    Directory of Open Access Journals (Sweden)

    Byeongsang Oh

    2014-01-01

    Full Text Available Background. Despite a number of in vitro and in vivo studies reporting the efficacy of fucoidan in treating various cancers, few studies have measured the efficacy of dietary fucoidan (DF in combination with cancer drugs. Thus, we examined the sensitivity of DF in combination with the EGFR/ERBB2-targeting reagent lapatinib on cancer cells. Method. We selected six EGFR/ERBB2-amplified cancer cell lines (OE19, NCI-N87, OE33, ESO26, MKN7, and BT474 as an in vitro model and tested their sensitivity to DF alone and to DF in combination with the well-known EGFR/ERBB2-targeting reagent lapatinib. Result. Overall, in drug independent sensitivity test, DF alone did not significantly inhibit the growth of EGFR/ERBB2-amplified cancer cells in vitro. When DF was given in combination with lapatinib, however, it tended to synergistically inhibit cell growth in OE33 but antagonized the action of lapatinib in ESO26, NCI-N87, and OE19. Conclusion. This study suggests that DF has the potential to increase or decrease the effects of certain anticancer drugs on certain cancer cell types. Further study is needed to explore the mechanism of interaction and synergistic antitumor activity of DF in combination with chemotherapy and targeted therapy.

  15. Anti-cancer effect of rubropunctatin against human gastric carcinoma cells BGC-823.

    Science.gov (United States)

    Zheng, Yunquan; Xin, Yanwen; Shi, Xianai; Guo, Yanghao

    2010-11-01

    The Monascus pigment, rubropunctatin, was extracted and purified from red mold rice (RMR) and its cytotoxic activities against human gastric adenocarcinoma BGC-823 cells were studied both in vitro and in vivo. Rubropunctatin inhibited the proliferation of BGC-823 cells with an inhibitory concentration (IC₅₀) of 12.57 μM, while it exhibited no significant toxicity to normal gastric epithelial cell GES-1 at the same concentration. Treatment of BGC-823 cells with rubropunctatin resulted in a dose- and time-dependent apoptosis, as validated by the increase in the percentage of cells in sub-G1 phase and phosphotidylserine externalization. The in vivo experimental data demonstrated that rubropunctatin could offer similar therapeutic benefits in comparison with the same dose of taxol. After five times of intravenous injection, tumor weight in BGC-823-bearing nude mice reduced 23.5% at the dose of 8 mg/kg and 37.7% at the dose of 32 mg/kg, respectively. The expressions of 30 genes related to induction of apoptosis were found up-regulated significantly. The two most expressed genes were tumor necrosis factor (TNF) and DNA-damage inducible transcript 3. TNF was considered as a major mediator of apoptosis induced by rubropunctatin. This is the first report describing the anti-proliferative effect of rubropunctatin and its apoptosis mechanism on BGC-823 cells. Rubropunctatin has potential to be developed as a new natural anti-cancer agent. PMID:20730532

  16. The anticancer effect and mechanism of α-hederin on breast cancer cells.

    Science.gov (United States)

    Cheng, Lin; Xia, Tian-Song; Wang, Yi-Fen; Zhou, Wenbin; Liang, Xiu-Qing; Xue, Jin-Qiu; Shi, Liang; Wang, Ying; Ding, Qiang; Wang, Minhai

    2014-08-01

    Natural plant products occupy a very important position in the area of cancer chemotherapy. Many triterpenoid saponins have been proved as potential agents for chemoprevention and therapy of breast cancer. α-hederin, a monodesmosidic triterpenoid saponin distributed in Hedera or Nigella species, displays many biological activities. It is increasingly investigated for its promising anticancer potential since it has been shown to have cytotoxicity against several types of cancer cells. However, studies of α-hederin on breast cancer are limited, most of which focus on biological activity, while the mechanisms have not been widely reported yet. Previously, we purified and identified α-hederin from Clematis ganpiniana, a herb used in traditional Chinese medicine with antitumor action. In the present study, α-hederin showed strong inhibitory activity on the growth of breast cancer cells and induced apoptosis in these cells. α-hederin induced depolarization of mitochondrial membrane potential which released Apaf-1 and cytochrome c from the intermembrane space into the cytosol, where they promoted caspase-3 and caspase-9 activation. This is the first report on the growth inhibition and pro-apoptotic effects of α-hederin on breast cancer cells and the relative apoptosis pathways. It implied that triterpenoid saponin α-hederin could be a promising candidate for chemotherapy of breast cancer. PMID:24842044

  17. Anticancer effect of arsenite on cell migration, cell cycle and apoptosis in human pancreatic cancer cells

    Science.gov (United States)

    HORIBE, YOHEI; ADACHI, SEIJI; YASUDA, ICHIRO; YAMAUCHI, TAKAHIRO; KAWAGUCHI, JUNJI; KOZAWA, OSAMU; SHIMIZU, MASAHITO; MORIWAKI, HISATAKA

    2016-01-01

    The standard treatment for advanced pancreatic cancer is chemotherapy, but its clinical outcome remains unsatisfactory. Therefore, the development of novel treatments for this malignancy is urgently required. In the present study, the anticancer effect of arsenite on platelet-derived growth factor (PDGF)-BB-induced migration, cell cycle and apoptosis was investigated in pancreatic cancer cells (AsPC-1 and BxPC-3), and compared with the effect on normal pancreatic epithelial (PE) cells. In the cell migration assay, arsenite clearly inhibited PDGF-BB-induced cell migration in AsPC-1 cells, but not in BxPC-3 or PE cells. Arsenite also caused cell apoptosis in AsPC-1 cells, but not in BxPC-3 or PE cells. In AsPC-1 cells, the levels of cyclin D1 and phosphorylated retinoblastoma protein decreased following treatment with arsenite, but this was not observed in BxPC-3 cells. To further examine the differences between these two cell lines, the effect of arsenite on upstream p44/p42 mitogen-activated protein kinase (MAPK) and Akt was investigated. PDGF-BB caused phosphorylation of p44/p42 MAPK and Akt in both cell lines. Pretreatment with arsenite significantly suppressed PDGF-BB-induced phosphorylation of Akt, but not of p44/p42 MAPK in AsPC-1 cells. By contrast, arsenite did not affect these molecules in BxPC-3 cells. Since the inhibition of the Akt signaling pathway markedly reduced PDGF-BB-induced migration in AsPC-1 cells, the present results strongly suggest that arsenite inhibits PDGF-BB-induced migration by suppressing the Akt signaling pathway in AsPC-1 cells. Therefore, arsenite may be a useful tool for the treatment of patients with certain types of pancreatic cancer, without causing adverse effects on normal pancreatic cells.

  18. Effect of Chromium on Antioxidant Potential of Catharanthus roseus Varieties and Production of Their Anticancer Alkaloids: Vincristine and Vinblastine

    OpenAIRE

    Vartika Rai; Pramod Kumar Tandon; Sayyada Khatoon

    2014-01-01

    Catharanthus roseus (L.) G. Don, a medicinal plant, has a very important place in the traditional as well as modern pharmaceutical industry. Two common varieties of this plant rosea and alba are named so because of pink and white coloured flowers, respectively. This plant comprises of about 130 terpenoid indole alkaloids and two of them, vincristine and vinblastine, are common anticancer drugs. The effect of chromium (Cr) on enzymatic and non-enzymatic antioxidant components and on secondary ...

  19. Self-assembling peptide-based nanoparticles enhance anticancer effect of ellipticine in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Wu Y

    2012-06-01

    Full Text Available Yan Wu,1,* Parisa Sadatmousavi,2,* Rong Wang,1 Sheng Lu,2 Yong-fang Yuan,1 P. Chen21Department of Pharmacy, No. 3 People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China; 2Department of Chemical Engineering, University of Waterloo, Waterloo, Ontario, Canada *Both authors contributed equally to this work.Background and methods: Applications of the anticancer agent, ellipticine, have been limited by its hydrophobicity and toxicity. An efficient delivery system is required to exploit the enormous potential of this compound. Recently, EAK16-II, an ionic-complementary, self-assembling peptide, has been found to stabilize ellipticine in aqueous solution. Here, the anticancer activity of ellipticine encapsulated in EAK16-II (EAK-EPT was evaluated in vitro and in vivo.Results: Our cellular uptake, toxicity, and apoptosis results in an A549 human lung carcinoma cell line indicate that EAK-EPT complexes are significantly more effective than treatment with EAK16-II or ellipticine alone. This is due to the ability of EAK16-II to stabilize ellipticine in a protonated state in well formed nanostructures approximately 200 nm in size. In vivo observations in an A549 nude mouse tumor model show higher antitumor activity and lower cytotoxicity of EAK-EPT complexes than in the control group treated with ellipticine alone. Tumor growth in animals was significantly inhibited after treatment with EAK-EPT complexes, and without any apparent side effects.Conclusion: The anticancer activity observed in this study coupled with minimal side effects encourages further development of peptide-mediated delivery of anticancer drugs, ellipticine in the present case, for clinical application.Keywords: self-assembling peptide, EAK16-II, ellipticine, nanoparticles, drug delivery, antitumor

  20. Anticancer effects and mechanisms of polysaccharide-K (PSK): implications of cancer immunotherapy.

    Science.gov (United States)

    Fisher, Monte; Yang, Li-Xi

    2002-01-01

    Polysaccharide-K (polysaccharide-Kureha; PSK), also known as krestin, is a unique protein-bound polysaccharide, which has been used as a chemoimmunotherapy agent in the treatment of cancer in Asia for over 30 years. PSK and Polysaccharopeptide (PSP) are both protein-bound polysaccharides which are derived from the CM-101 and COV-1 strains of the fungus Coriolus versicolor by Japanese and Chinese researchers, respectively. Both polysaccharide preparations have documented anticancer activity in vitro, in vivo and in human clinical trials, though PSK has been researched longer and has therefore undergone more thorough laboratory, animal and clinical testing. Several randomized clinical trials have demonstrated that PSK has great potential as an adjuvant cancer therapy agent, with positive results seen in the adjuvant treatment of gastric, esophageal, colorectal, breast and lung cancers. These studies have suggested the efficacy of PSK as an immunotherapy or biological response modifier (BRM). BRMs potentially have the ability to improve the "host versus tumor response," thereby increasing the ability of the host to defend itself from tumor progression. The mechanisms of biological response modification by PSK have yet to be clearly and completely elucidated. Some studies suggest that PSK may act to increase leukocyte activation and response through up-regulation of key cytokines. Indeed, natural killer (NK) and lymphocyte-activated killer (LAK) cell activation has been demonstrated in vivo and in vitro, and recent genetic studies reveal increased expression of key immune cytokines in response to treatment with PSK. An antimetastatic action of PSK has also been demonstrated and is perhaps attributed to its potential to inhibit metalloproteinases and other enzymes involved in metastatic activity. PSK has also been shown to cause differentiation of leukemic cells in vitro, and this effect has been attributed to induction of differentiation cytokines. PSK has further been

  1. Evidence to Support the Anti-Cancer Effect of Olive Leaf Extract and Future Directions

    Science.gov (United States)

    Boss, Anna; Bishop, Karen S.; Marlow, Gareth; Barnett, Matthew P. G.; Ferguson, Lynnette R.

    2016-01-01

    The traditional Mediterranean diet (MD) is associated with long life and lower prevalence of cardiovascular disease and cancers. The main components of this diet include high intake of fruit, vegetables, red wine, extra virgin olive oil (EVOO) and fish, low intake of dairy and red meat. Olive oil has gained support as a key effector of health benefits and there is evidence that this relates to the polyphenol content. Olive leaf extract (OLE) contains a higher quantity and variety of polyphenols than those found in EVOO. There are also important structural differences between polyphenols from olive leaf and those from olive fruit that may improve the capacity of OLE to enhance health outcomes. Olive polyphenols have been claimed to play an important protective role in cancer and other inflammation-related diseases. Both inflammatory and cancer cell models have shown that olive leaf polyphenols are anti-inflammatory and protect against DNA damage initiated by free radicals. The various bioactive properties of olive leaf polyphenols are a plausible explanation for the inhibition of progression and development of cancers. The pathways and signaling cascades manipulated include the NF-κB inflammatory response and the oxidative stress response, but the effects of these bioactive components may also result from their action as a phytoestrogen. Due to the similar structure of the olive polyphenols to oestrogens, these have been hypothesized to interact with oestrogen receptors, thereby reducing the prevalence and progression of hormone related cancers. Evidence for the protective effect of olive polyphenols for cancer in humans remains anecdotal and clinical trials are required to substantiate these claims idea. This review aims to amalgamate the current literature regarding bioavailability and mechanisms involved in the potential anti-cancer action of olive leaf polyphenols. PMID:27548217

  2. Effective rescue of anticancer immunity by temporary immunosuppressive treatment followed by immunostimulation: preliminary experimental results

    Czech Academy of Sciences Publication Activity Database

    Vannucci, Luca; Grobárová, Valeria; Saieh, M.; Richter, Jan; Strnádel, Ján; Fišerová, Anna

    2008-01-01

    Roč. 38, Suppl. 1 (2008), s. 40-41. ISSN 0014-2972. [42nd Annual Scientific Meeting of rhe European Society for Clinical Investigation. 26.4.-29.4.2008, Geneva] Institutional research plan: CEZ:AV0Z50450515; CEZ:AV0Z50200510 Keywords : anticancer immunity * immunosuppresive treatment * immunostimulatin Subject RIV: FD - Oncology ; Hematology

  3. The anticancer effects of sodium selenite and selenomethionine on human colorectal carcinoma cell lines in nude mice.

    Science.gov (United States)

    Yang, Yang; Huang, Fang; Ren, Yun; Xing, Lu; Wu, Ying; Li, Zhushi; Pan, Huazhen; Xu, Caimin

    2009-01-01

    The studies were carried out on nude mice bearing human colorectal carcinoma SW480 cell line xenografts to evaluate the chemotherapeutic potential of selenium containing compounds such as sodium selenite (SSe) and selenomethionine (SeMet). Three doses of anticancer drugs were used, including 0.1 mg/kg/day SSe (LSSe), 2 mg/kg/day SSe (HSSe), and 2 mg/kg/day SeMet. We explored the anticancer effect of SSe and SeMet administered by IP injection for 21 days. We observed the pathologic changes and the cell apoptosis in tumor tissue by HE staining and TUNNEL assay after HSSe and SeMet treatment. GSH level and antioxidant enzyme GPX activity in tumor tissues were assessed. In addition, Western blotting was used to detect the expression of apoptosis-related proteins. The results suggested that HSSe and SeMet had significantly inhibited tumor growth in vivo. We also observed the pathologic changes and cell apoptosis in tumor tissues after HSSe and SeMet treatment. GSH level was a bit increased but the GPX activity was reduced. Moreover, SSe and SeMet treatment downregulated the expression of the protein Bcl-xL, increased the expression of Bax, Bad, and Bim, and activated caspase-9. SSe and SeMet may be the selective, low-toxic anticancer agents to treat human colorectal carcinoma cancer. PMID:19911698

  4. Zinc finger protein 521 overexpression increased transcript levels of Fndc5 in mouse embryonic stem cells

    Indian Academy of Sciences (India)

    Motahere-Sadat Hashemi; Abbas Kiani Esfahani; Maryam Peymani; Alireza Shoaraye Nejati; Kamran Ghaedi; Mohammad Hossein Nasr-Esfahani; Hossein Baharvand

    2016-03-01

    Zinc finger protein 521 is highly expressed in brain, neural stem cells and early progenitors of the human hematopoietic cells. Zfp521 triggers the cascade of neurogenesis inmouse embryonic stemcells through inducing expression of the early neuroectodermal genes Sox1, Sox3 and Pax6. Fndc5, a precursor of Irisin has inducing effects on the expression level of brain derived neurotrophic factor in hippocampus. Therefore, it is most likely that Fndc5 may play an important role in neural differentiation. To exhibit whether the expression of this protein is under regulation with Zfp521, we overexpressed Zfp521 in a stable transformants of mESCs expressing EGFP under control of Fndc5 promoter. Increased expression of Zfp521 enhanced transcription levels of both EGFP and endogenous Fndc5. This result was confirmed by overexpression the aforementioned vectors in HEK cells and indicated that Zfp521 functions upstream of Fndc5 expression. It is most likely that Zfp521 may act through the binding to its response element on Fndc5 core promoter. Therefore it is concluding that an enhanced expression of Fndc5 in neural progenitor cells is stimulated by Zfp521 overexpression in these cells.

  5. Anticancer Effects of 1,3-Dihydroxy-2-Methylanthraquinone and the Ethyl Acetate Fraction of Hedyotis Diffusa Willd against HepG2 Carcinoma Cells Mediated via Apoptosis

    OpenAIRE

    Li, Yun-lan; Zhang, Jiali; Min, Dong; Hongyan, Zhou; Lin, Niu; Li, Qing-Shan

    2016-01-01

    Hedyotis Diffusa Willd, used in Traditional Chinese Medicine, is a treatment for various diseases including cancer, owing to its mild effectiveness and low toxicity. The aim of this study was to identify the main anticancer components in Hedyotis Diffusa Willd, and explore mechanisms underlying their activity. Hedyotis Diffusa Willd was extracted and fractionated using ethyl acetate to obtain the H-Ethyl acetate fraction, which showed higher anticancer activity than the other fractions obtain...

  6. Curcumin-albumin conjugates as an effective anti-cancer agent with immunomodulatory properties.

    Science.gov (United States)

    Aravind, S R; Krishnan, Lissy K

    2016-05-01

    Curcumin (diferuloylmethane) is an active ingredient in turmeric (Curcuma longa) with anti-inflammatory, antioxidant, chemopreventive, chemosensitization, and radiosensitization properties. Conjugation of curcumin (Curc) to albumin (Alb) has been found to increase the aqueous solubility of the drug. The current study aimed to prove the safe use of the Curc-Alb conjugate in animals and to demonstrate that it retains drug action both in vitro and in vivo. Dalton's lymphoma ascites (DLA) cell viability was inhibited by the Curc-Alb conjugate in a dose dependent manner in vitro, as evidenced by the MTT assay. Administration of up to 11.4 mg of conjugated curcumin per kg body weight to healthy animals was non-toxic both in terms of lethality and weight loss. Histological analysis of vital organs (kidney, liver and spleen) also did not show toxic effects. Favorable immuno-modulatory activity was observed after continuous administration of sub-acute doses of the conjugate which caused increase in total leukocyte count, platelet count, and viable cell count in bone marrow, and enhanced proliferation of lymphocyte in vitro upon culture. In vivo studies in the DLA tumor model in mice demonstrated that conjugated drug induces tumor reduction and prevention. Significant tumor reduction was observed when the Curc-Alb conjugate was administered intraperitoneally in DLA-induced mice after 1 day (prevention therapy) and 7 days (reduction therapy) of tumor induction. There was significant reduction in both tumor volume and tumor cell numbers in the treated animals as well as a marked increase in their mean survival time and percent increase in life span. The effect was greater when the conjugate was administered soon after inducing the tumor as compared to when treatment was started after allowing tumor to grow for 7 days. Thus, the results of the present study suggest that curcumin albumin conjugate has immunomodulatory and tumor growth inhibition properties. The study postulates

  7. ANTICANCER EFFECTS OF CARICA PAPAYA IN EXPERIMENTAL INDUCED MAMMARY TUMORS IN RATS

    Directory of Open Access Journals (Sweden)

    Gurudatta M, Deshmukh YA, Naikwadi A A

    2015-07-01

    Full Text Available Objective: To evaluate the anticancer effect of Carica papaya in DMBA induced mammary tumors in rats. Methods: Wistar rats were divided in to five groups (n=6, Group-I (Normal control administered vehicle olive oil, Group-II, Group-III ,Group-IV and V induced mammary tumors by administering single dose of DMBA (7,12 Dimethyl benz(Aanthracene orally 65 mg/kg. Group-III was administered aqueous leaf extract of Carica papaya (ALQECP in a dose of 200 mg/kg body wt for a period of 3 months, group-IV has given ALQECP 200 mg/kg body wt for a period of 21 days post 3 months of tumor induction, group-V rats were administered a small dose of Carica papaya extract intra tumor locally in the region of tumor. Results: Values of CA15-3 were increased in group-II rats (tumor control significantly, whereas in group-III (prevention group the levels of CA15-3 were found to be reduced substantially and the P value < 0.001. Similarly, CA-15-3 levels were reduced significantly in group-IV (treatment groupand P<0.005. The levels of LDH were seen to be increased in group-II, where as in group-III LDH levels were decreased and P<0.001.similarly group-IV LDH levels also reduced significantly but not to the level of group-III. Conclusion: Among the various markers for the detection of cancer antigen-15(CA15-3 and lactate dehydrogenase (LDH are important biochemical parameters that give a clear understanding of the progression and proliferation of cancer cells. In this study it was found that there is increase in the levels of markers such as CA15-3 and LDH and also the tumor volume in tumor control, these marker levels were decreased by the administration of aqueous leaf extract of Carica papaya in a dose of 200 mg/kg body wt. ALQECP not only prevented the progression of cancer growth but also has significant effect in reducing the both CA15-3 and LDH levels in treatment group.

  8. Anticancer Effects of Different Seaweeds on Human Colon and Breast Cancers

    Directory of Open Access Journals (Sweden)

    Ghislain Moussavou

    2014-09-01

    Full Text Available Seafoods and seaweeds represent some of the most important reservoirs of new therapeutic compounds for humans. Seaweed has been shown to have several biological activities, including anticancer activity. This review focuses on colorectal and breast cancers, which are major causes of cancer-related mortality in men and women. It also describes various compounds extracted from a range of seaweeds that have been shown to eradicate or slow the progression of cancer. Fucoidan extracted from the brown algae Fucus spp. has shown activity against both colorectal and breast cancers. Furthermore, we review the mechanisms through which these compounds can induce apoptosis in vitro and in vivo. By considering the ability of compounds present in seaweeds to act against colorectal and breast cancers, this review highlights the potential use of seaweeds as anticancer agents.

  9. Anticancer efficacy enhancement and attenuation of side effects of doxorubicin with titanium dioxide nanoparticles

    OpenAIRE

    Chen Y; Wan Y; Wang Y; Zhang H.; Jiao Z

    2011-01-01

    Yan Chen1,*, Ying Wan1,*, Yi Wang1, Haijun Zhang2, Zhijun Jiao11Key Laboratory of Medical Immunology and Department of Laboratory Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang; 2Department of Oncology, Zhongda Hospital, Medical School, Southeast University, Nanjing, People’s Republic of China *These authors have contributed equally to this workBackground: Doxorubicin has a broad spectrum of anticancer activity, but its clinical application is limited due to serious ...

  10. Effect of selected ABC-drug transporters and anticancer drug disposition in vitro and in vivo

    OpenAIRE

    Marchetti, S

    2013-01-01

    Studies described in the thesis that is lying in front of you aim to address the possible implications of selected ABC-drug transporters on the disposition of a number of important anticancer drugs. Although variability in drug disposition has been known for as long as pharmacological studies supported drug development and clinical therapeutics general molecular pharmacological concepts explaining the given interpatient variation in drug disposition have been lacking for many decades. Firm ex...

  11. Anticancer Effect of Ursodeoxycholic Acid in Human Oral Squamous Carcinoma HSC-3 Cells through the Caspases

    Directory of Open Access Journals (Sweden)

    Liang Pang

    2015-05-01

    Full Text Available Bear bile was used as a traditional medicine or tonic in East Asia, and ursodeoxycholic acid (UDCA is the most important compound in bear bile. Further, synthetic UDCA is also used in modern medicine and nutrition; therefore, its further functional effects warrant research, in vitro methods could be used for the fundamental research of its anticancer effects. In this study, the apoptotic effects of UDCA in human oral squamous carcinoma HSC-3 cells through the activation of caspases were observed by the experimental methods of MTT (3-(4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2-H-tetrazolium bromide assay, DAPI (4’,6-diamidino-2-phenylindole staining, flow cytometry analysis, RT-PCR (reverse transcription-polymerase chain reaction assay and Western blot assay after HSC-3 cells were treated by different concentrations of UDCA. With 0 to 400 μg/mL UDCA treatment, UDCA had strong growth inhibitory effects in HSC-3 cells, but had almost no effect in HOK normal oral cells. At concentrations of 100, 200 and 400 μg/mL, UDCA could induce apoptosis compared to untreated control HSC-3 cells. Treatment of 400 μg/mL UDCA could induce more apoptotic cancer cells than 100 and 200 μg/mL treatment; the sub-G1 DNA content of 400 μg/mL UDCA treated cancer cells was 41.3% versus 10.6% (100 μg/mL and 22.4% (200 μg/mL. After different concentrations of UDCA treatment, the mRNA and protein expressions of caspase-3, caspase-8, caspase-9, Bax, Fas/FasL (Fas ligand, TRAIL (TNF-related apoptosis-inducing ligand, DR4 (death receptor 4 and DR5 (death receptor 5 were increased in HSC-3 cells, and mRNA and protein expressions of Bcl-2 (B-cell lymphoma 2, Bcl-xL (B-cell lymphoma-extra large, XIAP (X-linked inhibitor of apoptosis protein, cIAP-1 (cellular inhibitor of apoptosis 1, cIAP-2 (cellular inhibitor of apoptosis 2 and survival were decreased. Meanwhile, at the highest concentration of 400 μg/mL, caspase-3, caspase-8, caspase-9, Bax, Fas/FasL, TRAIL, DR4, DR5, and

  12. Soy Isoflavone Genistein-Mediated Downregulation of miR-155 Contributes to the Anticancer Effects of Genistein

    Science.gov (United States)

    de la Parra, Columba; Castillo-Pichardo, Linette; Cruz-Collazo, Ailed; Cubano, Luis; Redis, Roxana; Calin, George A.; Dharmawardhane, Suranganie

    2016-01-01

    We previously reported that dietary genistein inhibits mammary tumor growth and metastasis of the highly metastatic MDA-MB-435 cancer cells in immunocompromised mice. The purpose herein was to characterize the role of the novel oncogenic microRNA (miRNA) miR-155 in the anticancer effects of genistein in metastatic breast cancer. The effect of genistein was determined on breast cancer cell viability, apoptosis, and expression of miR-155 and its targets. At low physiologically relevant concentrations, genistein inhibits cell viability and induces apoptosis in metastatic MDA-MB-435 and Hs578t breast cancer cells, without affecting the viability of nonmetastatic MCF-7 breast cancer cells. In parallel with reduced cell viability, miR-155 is downregulated, whereas proapoptotic and anticell proliferative miR-155 targets FOXO3, PTEN, casein kinase, and p27 are upregulated in MDA-MB-435 and Hs578t cells in response to genistein treatment. However, miR-155 levels remain unchanged in response to genistein in the MCF-7 cells. Ectopic expression of miR-155 in MDA-MB-435 and Hs578t cells decreases the effects of genistein on cell viability and abrogates the effects of genistein on apoptosis and expression of proapoptotic genes. Therefore, genistein-mediated downregulation of miR-155 contributes to the anticancer effects of genistein in metastatic breast cancer. PMID:26771440

  13. Induction of c-Cbl contributes to anti-cancer effects of HDAC inhibitor in lung cancer

    OpenAIRE

    Wei, Tzu-Tang; Lin, Yu-Chin; Lin, Pei-Hua; Shih, Jin-Yuan; Chou, Chia-Wei; Huang, Wei-Jan; Yang, Yu-Chih; Hsiao, Pei-Wen; Chen, Ching-Chow

    2015-01-01

    Here we found loss of c-Cbl, an E3 ligase, expression in non-small cell lung cancer (NSCLC) compared with its adjacent normal tissue in patient specimens. HDAC inhibition by WJ or knockdown of HDAC 1, HDAC2, HDAC3 or HDAC6 all induced c-Cbl. Ectopic expression of c-Cbl induced decreased EGFR, inhibited growth in NSCLC cells. Knockdown of EGFR inhibited NSCLC growth. Mutation of EGFR at Y1045 decreased WJ-induced growth inhibition as well as in vivo anti-cancer effect and EGFR degradation medi...

  14. Opioid receptor activation triggering downregulation of cAMP improves effectiveness of anti-cancer drugs in treatment of glioblastoma

    Science.gov (United States)

    Friesen, Claudia; Hormann, Inis; Roscher, Mareike; Fichtner, Iduna; Alt, Andreas; Hilger, Ralf; Debatin, Klaus-Michael; Miltner, Erich

    2014-01-01

    Glioblastoma are the most frequent and malignant human brain tumors, having a very poor prognosis. The enhanced radio- and chemoresistance of glioblastoma and the glioblastoma stem cells might be the main reason why conventional therapies fail. The second messenger cyclic AMP (cAMP) controls cell proliferation, differentiation, and apoptosis. Downregulation of cAMP sensitizes tumor cells for anti-cancer treatment. Opioid receptor agonists triggering opioid receptors can activate inhibitory Gi proteins, which, in turn, block adenylyl cyclase activity reducing cAMP. In this study, we show that downregulation of cAMP by opioid receptor activation improves the effectiveness of anti-cancer drugs in treatment of glioblastoma. The µ-opioid receptor agonist D,L-methadone sensitizes glioblastoma as well as the untreatable glioblastoma stem cells for doxorubicin-induced apoptosis and activation of apoptosis pathways by reversing deficient caspase activation and deficient downregulation of XIAP and Bcl-xL, playing critical roles in glioblastomas’ resistance. Blocking opioid receptors using the opioid receptor antagonist naloxone or increasing intracellular cAMP by 3-isobutyl-1-methylxanthine (IBMX) strongly reduced opioid receptor agonist-induced sensitization for doxorubicin. In addition, the opioid receptor agonist D,L-methadone increased doxorubicin uptake and decreased doxorubicin efflux, whereas doxorubicin increased opioid receptor expression in glioblastomas. Furthermore, opioid receptor activation using D,L-methadone inhibited tumor growth significantly in vivo. Our findings suggest that opioid receptor activation triggering downregulation of cAMP is a promising strategy to inhibit tumor growth and to improve the effectiveness of anti-cancer drugs in treatment of glioblastoma and in killing glioblastoma stem cells. PMID:24626197

  15. Effect of anticancer therapy on Tn antigen exposure on the leucocyte membranes in patients with leukemia

    Directory of Open Access Journals (Sweden)

    G. S. Maslak

    2014-08-01

    Full Text Available Tn-antigen (Thomsen-nouvelle antigen is tumor-associated carbohydrate antigen with only one GalNAc residue attached to serine or threonine of polypeptide chain. There is not enough data about the expression of this glycotope in hematologic processes. But the correlations between increasing Tn-antigen expression on the cell surface and tumor growth progression, invasion, and activation of cell migration are well known. Therefore, the currently important area of modern research is studying of the impact of anticancer therapy by expression of this carbohydrate antigen in the onco-proliferative process. There are two types of cytostatic therapies in clinical hospitals of Ukraine: COP-therapy (cyclophosphamide, vincristine, prednisone and FC-therapy (fludarabine, cyclophosphamide, which are the most popular due to their effectiveness and low price. The aim of our study was to investigate Tn-antigen exposure on the surface of lymphocytes, monocytes and granulocytes in polycythemia vera and subleukemic myelosis; to examine the influence of COP- and FC-therapies on Tn-antigen exponation in patients with chronic lymphocytic leukemia. The objects of the study were blood cells of patients with chronic lymphocytic leukemia (n = 25, polycythemia vera (n = 15 and subleukemic myelosis (n = 15 aged 58–66 years. Healthy hematologic volunteers (n = 15 aged 55 to 65 years were in the control group. Lymphocytes of patients with chronic lymphocytic leukemia (n = 25 were also studied after the chemotherapy treatment of patients divided into two groups: those who took COP-therapy (n = 13; and those who treated with FC-therapy (n = 12. Tn-antigen exposure on lymphocytes, monocytes and granulocytes was investigated by Beckman Сoulter EPICS flow cytometer with primary monoclonal Tn-antigen anybodies (Institute of Immunology, Moscow, Russia and secondary fluorescein isothiocyanate labeled antybodies (Millipore, USA. The number of dead cells was monitored by binding

  16. Hepatoprotective, Antioxidant, and Anticancer Effects of the Tragopogon porrifolius Methanolic Extract

    OpenAIRE

    Clara Tenkerian; Mirvat El-Sibai; Costantine F. Daher; Mohamad Mroueh

    2015-01-01

    Tragopogon porrifolius (Asteraceae), commonly referred to as white salsify, is an edible herb used in Lebanese folk medicine to treat cancer and liver dysfunction. In this study, we investigated the antioxidant activity of Tragopogon porrifolius methanolic extract, both in vitro and in vivo, in addition to its hepatoprotective and anticancer activities. Total phenolic and flavonoid contents were measured and found to be 37.0 ± 1.40 mg GAE/g and 16.6 ± 0.42 mg QE/g dry weight, respectively. In...

  17. Nanofabrication of methylglyoxal with chitosan biopolymer: a potential tool for enhancement of its anticancer effect

    Directory of Open Access Journals (Sweden)

    Pal A

    2015-05-01

    Full Text Available Aparajita Pal,1,* Dipa Talukdar,1,* Anirban Roy,1 Subhankar Ray,2 Asish Mallick,3 Chitra Mandal,3 Manju Ray1 1Department of Biophysics, Bose Institute, Kolkata, India; 2Department of Biochemistry, University of Calcutta, Kolkata, India; 3Cancer Biology and Inflammatory Disorder Division, Council of Scientific and Industrial Research (CSIR-Indian Institute of Chemical Biology, Kolkata, India *These authors contributed equally to this work Purpose: The normal metabolite methylglyoxal (MG specifically kills cancer cells by inhibiting glycolysis and mitochondrial respiration without much adverse effect upon normal cells. Though the anticancer property of MG is well documented, its gradual enzymatic degradation in vivo has prompted interest in developing a nanoparticulate drug delivery system to protect it and also to enhance its efficacy. Materials and methods: MG-conjugated chitosan nanoparticles (Nano-MG were prepared by conjugating the carbonyl group of MG with the amino group of chitosan polymer (Schiff’s base formation. Nano-MG were characterized in detail using the dynamic light scattering method, zeta potential measurement, Fourier transform infrared spectroscopy, and transmission electron microscopic analysis. Amount of MG anchored to Nano-MG, stability of Nano-MG, and in vitro release of MG from Nano-MG were estimated spectrophotometrically. Ehrlich ascites carcinoma (EAC cells, human breast cancer cell line HBL-100, and lung epithelial adenocarcinoma cell line A549 were used as test systems to compare Nano-MG with bare MG in vitro. Cytotoxicity to EAC cells was evaluated by the trypan blue dye exclusion test, and cell viability of HBL-100 and A549 cells were studied using 3-(4,5-dimethylthiazol-2-yl 2,5-diphenyltetrazolium bromide (MTT assay. Apoptosis of HBL-100 cells was assessed by flow cytometry and confocal microscopy. In vivo studies were performed on both EAC cells inoculated and also in sarcoma-180-induced solid tumor

  18. Layered double hydroxides as effective carrier for anticancer drugs and tailoring of release rate through interlayer anions.

    Science.gov (United States)

    Senapati, Sudipta; Thakur, Ravi; Verma, Shiv Prakash; Duggal, Shivali; Mishra, Durga Prasad; Das, Parimal; Shripathi, T; Kumar, Mohan; Rana, Dipak; Maiti, Pralay

    2016-02-28

    Hydrophobic anticancer drug, raloxifene hydrochloride (RH) is intercalated into a series of magnesium aluminum layered double hydroxides (LDHs) with various charge density anions through ion exchange technique for controlled drug delivery. The particle nature of the LDH in presence of drug is determined through electron microscopy and surface morphology. The release of drug from the RH intercalated LDHs was made very fast or sustained by altering the exchangeable anions followed by the modified Freundlich and parabolic diffusion models. The drug release rate is explained from the interactions between the drug and LDHs along with order-disorder structure of drug intercalated LDHs. Nitrate bound LDH exhibits greater interaction with drug and sustained drug delivery against the loosely interacted phosphate bound LDH-drug, which shows fast release. Cell viability through MTT assay suggests drug intercalated LDHs as better drug delivery vehicle for cancer cell line against poor bioavailability of the pure drug. In vivo study with mice indicates the differential tumor healing which becomes fast for greater drug release system but the body weight index clearly hints at damaged organ in the case of fast release system. Histopathological experiment confirms the damaged liver of the mice treated either with pure drug or phosphate bound LDH-drug, fast release system, vis-à-vis normal liver cell morphology for sluggish drug release system with steady healing rate of tumor. These observations clearly demonstrate that nitrate bound LDH nanoparticle is a potential drug delivery vehicle for anticancer drugs without any side effect. PMID:26774219

  19. In vitro bioassays for anticancer drug screening: effects of cell concentration and other assay parameters on growth inhibitory activity.

    Science.gov (United States)

    Lieberman, M M; Patterson, G M; Moore, R E

    2001-11-01

    In vitro growth inhibition assays were performed using human cancer cell lines at various concentrations with experimental anticancer drugs such as the cryptophycins and other cytotoxins. The effect of variations in assay parameters on the observed growth inhibition of these anticancer therapeutic agents was determined. The results demonstrated that the observed inhibitory activity of these compounds varied inversely with the cell concentrations used. The observed differences in activity between different cytotoxins were not necessarily proportionate. Thus, the relative activities of two toxins also varied with cell concentration. Furthermore, the sensitivity of these cell lines to the cytostatic purine analog, 6-mercaptopurine (used as a control), varied with cell concentration as well. The activity of this compound was dependent on the medium used for cell growth, yielding good activity in Eagle's minimum essential medium, but not in Ham's F-12 (Kaigin) medium. Moreover, growth inhibition by cryptophycin as well as 6-mercaptopurine was also dependent on the serum concentration in the medium. Finally, the sensitivity of the cancer cell lines to various organic solvents commonly used as drug vehicles for in vitro testing, such as ethanol, dimethylformamide, and dimethylsulfoxide, was likewise found to vary inversely with cell concentration. PMID:11578805

  20. Anticancer Effects of 1,3-Dihydroxy-2-Methylanthraquinone and the Ethyl Acetate Fraction of Hedyotis Diffusa Willd against HepG2 Carcinoma Cells Mediated via Apoptosis.

    Science.gov (United States)

    Li, Yun-Lan; Zhang, Jiali; Min, Dong; Hongyan, Zhou; Lin, Niu; Li, Qing-Shan

    2016-01-01

    Hedyotis Diffusa Willd, used in Traditional Chinese Medicine, is a treatment for various diseases including cancer, owing to its mild effectiveness and low toxicity. The aim of this study was to identify the main anticancer components in Hedyotis Diffusa Willd, and explore mechanisms underlying their activity. Hedyotis Diffusa Willd was extracted and fractionated using ethyl acetate to obtain the H-Ethyl acetate fraction, which showed higher anticancer activity than the other fractions obtained against HepG2 cells with sulforhodamine B assays. The active component of the H-Ethyl acetate fraction was identified to be 1,3-dihydroxy-2-methylanthraquinone (DMQ) with much high inhibitory rate up to 48.9 ± 3.3% and selectivity rate up to 9.4 ± 4.5 folds (pHedyotis Diffusa Willd showed potential anticancer effects. Furthermore, the mechanisms of action may involve mitochondrial apoptotic and death receptor pathways. PMID:27064569

  1. Anticancer effect and mechanism of polymer micelle-encapsulated quercetin on ovarian cancer

    Science.gov (United States)

    Gao, Xiang; Wang, Bilan; Wei, Xiawei; Men, Ke; Zheng, Fengjin; Zhou, Yingfeng; Zheng, Yu; Gou, Maling; Huang, Meijuan; Guo, Gang; Huang, Ning; Qian, Zhiyong; Wei, Yuquan

    2012-10-01

    Encapsulation of hydrophobic agents in polymer micelles can improve the water solubility of cargos, contributing to develop novel drugs. Quercetin (QU) is a hydrophobic agent with potential anticancer activity. In this work, we encapsulated QU into biodegradable monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles and tried to provide proof-of-principle for treating ovarian cancer with this nano-formulation of quercetin. These QU loaded MPEG-PCL (QU/MPEG-PCL) micelles with drug loading of 6.9% had a mean particle size of 36 nm, rendering the complete dispersion of quercetin in water. QU inhibited the growth of A2780S ovarian cancer cells on a dose dependent manner in vitro. Intravenous administration of QU/MPEG-PCL micelles significantly suppressed the growth of established xenograft A2780S ovarian tumors through causing cancer cell apoptosis and inhibiting angiogenesis in vivo. Furthermore, the anticancer activity of quercetin on ovarian cancer cells was studied in vitro. Quercetin treatment induced the apoptosis of A2780S cells associated with activating caspase-3 and caspase-9. MCL-1 downregulation, Bcl-2 downregulation, Bax upregulation and mitochondrial transmembrane potential change were observed, suggesting that quercetin may induce apoptosis of A2780S cells through the mitochondrial apoptotic pathway. Otherwise, quercetin treatment decreased phosphorylated p44/42 mitogen-activated protein kinase and phosphorylated Akt, contributing to inhibition of A2780S cell proliferation. Our data suggested that QU/MPEG-PCL micelles were a novel nano-formulation of quercetin with a potential clinical application in ovarian cancer therapy.

  2. Heterocyclic chalcone analogues as potential anticancer agents.

    Science.gov (United States)

    Sharma, Vikas; Kumar, Vipin; Kumar, Pradeep

    2013-03-01

    Chalcones, aromatic ketones and enones acting as the precursor for flavonoids such as Quercetin, are known for their anticancer effects. Although, parent chalcones consist of two aromatic rings joined by a three-carbon α,β-unsaturated carbonyl system, various synthetic compounds possessing heterocyclic rings like pyrazole, indole etc. are well known and proved to be effective anticancer agents. In addition to their use as anticancer agents in cancer cell lines, heterocyclic analogues are reported to be effective even against resistant cell lines. In this connection, we hereby highlight the potential of various heterocyclic chalcone analogues as anticancer agents with a brief summary about therapeutic potential of chalcones, mechanism of anticancer action of various chalcone analogues, and current and future prospects related to the chalcones-derived anticancer research. Furthermore, some key points regarding chalcone analogues have been reviewed by analyzing their medicinal properties. PMID:22721390

  3. Synthesis of some new heterocyclic compounds bearing a sulfonamide moiety and studying their combined anticancer effect with γ-radiation

    International Nuclear Information System (INIS)

    In search for new cytotoxic agents with improved anticancer profile, some new halogen-containing quinoline and pyrimido[4,5-b]quinoline derivatives bearing a free sulfonamide moiety were synthesized. All the newly synthesized target compounds were subjected to in vitro anticancer screening against human breast cancer cell line (MCF7). The most potent compounds, as concluded from the in vitro anticancer screening, were selected to be evaluated again for their in vitro anticancer activity in combination with radiation. Also, the newly synthesized compounds were docked in the active site of the carbonic anhydrase enzyme

  4. Combinatorial anticancer effects of curcumin and sorafenib towards thyroid cancer cells via PI3K/Akt and ERK pathways.

    Science.gov (United States)

    Zhang, Junjia; Yu, Jichun; Xie, Rong; Chen, Wanzhi; Lv, Yunxia

    2016-08-01

    The objective of this study was to examine the in vitro combinatorial anticancer effects of curcumin and sorafenib towards thyroid cancer cells FTC133 using a MTT cytotoxicity assay, and to test whether the mechanism involves induction of apoptosis. The present results demonstrated that curcumin at 15-25 μM dose-dependently suppressed the proliferation of FTC133. Combined treatment (curcumin (25 μM) and sorafenib (2 μM)) resulted in a reduction in cell colony formation and significantly decreased the invasion and migration of FTC133 cells compared with that treated with individual drugs. Western blot showed that the levels of p-ERK and p-Akt proteins were significantly reduced (p curcumin was found to dose-dependently inhibit the apoptosis of FTC133 cells possibly via PI3K/Akt and ERK pathways. There is a synergetic antitumour effect between curcumin and sorafenib. PMID:26299635

  5. Colon-available raspberry polyphenols exhibit anti-cancer effects on in vitro models of colon cancer

    Directory of Open Access Journals (Sweden)

    McDougall Gordon

    2007-01-01

    Full Text Available Abstract Background There is a probable association between consumption of fruit and vegetables and reduced risk of cancer, particularly cancer of the digestive tract. This anti-cancer activity has been attributed in part to anti-oxidants present in these foods. Raspberries in particular are a rich source of the anti-oxidant compounds, such as polyphenols, anthocyanins and ellagitannins. Methods A "colon-available" raspberry extract (CARE was prepared that contained phytochemicals surviving a digestion procedure that mimicked the physiochemical conditions of the upper gastrointestinal tract. The polyphenolic-rich extract was assessed for anti-cancer properties in a series of in vitro systems that model important stages of colon carcinogenesis, initiation, promotion and invasion. Results The phytochemical composition of CARE was monitored using liquid chromatography mass spectrometry. The colon-available raspberry extract was reduced in anthocyanins and ellagitannins compared to the original raspberry juice but enriched in other polyphenols and polyphenol breakdown products that were more stable to gastrointestinal digestion. Initiation – CARE caused significant protective effects against DNA damage induced by hydrogen peroxide in HT29 colon cancer cells measured using single cell microgelelectrophoresis. Promotion – CARE significantly decreased the population of HT29 cells in the G1 phase of the cell cycle, effectively reducing the number of cells entering the cell cycle. However, CARE had no effect on epithelial integrity (barrier function assessed by recording the trans-epithelial resistance (TER of CACO-2 cell monolayers. Invasion – CARE caused significant inhibition of HT115 colon cancer cell invasion using the matrigel invasion assay. Conclusion The results indicate that raspberry phytochemicals likely to reach the colon are capable of inhibiting several important stages in colon carcinogenesis in vitro.

  6. The Study on Acute and Subacute Toxicity and Anti-Cancer Effects of cultivated wild ginseng Herbal acupuncture

    Directory of Open Access Journals (Sweden)

    Ki-Rok, Kwon

    2003-06-01

    Full Text Available Objectives : The purpose of this study was to investigate acute and subacute toxicity and sarcoma-180 anti-cancer effects of herbal acupuncture with cultivated wild ginseng (distilled in mice and rats. Methods : Balb/c mice were injected intravenous with cultivated wild ginseng herbal acupuncture for LD50 and acute toxicity test. Sprague-Dawley rats were injected intravenous with cultivated wild ginseng herbal acupuncture for subacute toxicity test. The cultivated wild ginseng herbal-acupuncture was injected at the tail vein of mice. Results : 1. In acute LD50 toxicity test, there was no mortality thus unable to attain the value. 2. Examining the toxic response in the acute toxicity test, there was no sign of toxication. 3. In acute toxic test, running biochemical serum test couldn't yield any differences between the control and experiment groups. 4. In subacute toxicity test, there was no sign of toxication in the experimental groups and didn't show any changes in weight compared to the normal group. 5. In subacute toxicity test, biochemical serum test showed significant increase of Total albumin, Albumin, and Glucose in the experimental group I compared with the control group. Significant decrease of GOT, ALP, GPT, and Triglyceride were shown. In experiment group II, only Glucose showed significant increase compared with the control group. 6. Measuring survival rate for anti-cancer effects of Sarcoma-180 cancer cell line, all the experimental groups showed significant increase in survival rate. 7. Measuring NK cell activity rate, no significant difference was shown throughout the groups. 8. Measuring Interleukin-2 productivity rate, all the experimental groups didn't show significant difference. 9. For manifestation of cytokine mRNA, significant decrease of interleukin-10 was witnessed in the experimental group compared to the control group. Conclusion : According to the results, we can conclude cultivated wild ginseng herbal acupuncture

  7. Differential Effects of Thidiazuron on Production of Anticancer Phenolic Compounds in Callus Cultures of Fagonia indica.

    Science.gov (United States)

    Khan, Tariq; Abbasi, Bilal Haider; Khan, Mubarak Ali; Shinwari, Zabta Khan

    2016-04-01

    Fagonia indica, a very important anticancer plant, has been less explored for its in vitro potential. This is the first report on thidiazuron (TDZ)-mediated callogenesis and elicitation of commercially important phenolic compounds. Among the five different plant growth regulators tested, TDZ induced comparatively higher fresh biomass, 51.0 g/100 mL and 40.50 g/100 mL for stem and leaf explants, respectively, after 6 weeks of culture time. Maximum total phenolic content (202.8 μg gallic acid equivalent [GAE]/mL for stem-derived callus and 161.3 μg GAE/mL for leaf-derived callus) and total flavonoid content (191.03 μg quercetin equivalent [QE]/mL for stem-derived callus and 164.83 μg QE/mL for leaf-derived callus) were observed in the optimized callus cultures. The high-performance liquid chromatography (HPLC) data indicated higher amounts of commercially important anticancer secondary metabolites such as gallic acid (125.10 ± 5.01 μg/mL), myricetin (32.5 ± 2.05 μg/mL), caffeic acid (12.5 ± 0.52 μg/mL), catechin (9.4 ± 1.2 μg/mL), and apigenin (3.8 ± 0.45 μg/mL). Owing to the greater phenolic content, a better 2-2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity (69.45 % for stem explant and 63.68 % for leaf explant) was observed in optimized calluses. The unusually higher biomass and the enhanced amount of phenolic compounds as a result of lower amounts of TDZ highlight the importance of this multipotent hormone as elicitor in callus cultures of F. indica. PMID:26758711

  8. The slow-releasing hydrogen sulfide donor, GYY4137, exhibits novel anti-cancer effects in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Zheng Wei Lee

    Full Text Available The slow-releasing hydrogen sulfide (H₂S donor, GYY4137, caused concentration-dependent killing of seven different human cancer cell lines (HeLa, HCT-116, Hep G2, HL-60, MCF-7, MV4-11 and U2OS but did not affect survival of normal human lung fibroblasts (IMR90, WI-38 as determined by trypan blue exclusion. Sodium hydrosulfide (NaHS was less potent and not active in all cell lines. A structural analogue of GYY4137 (ZYJ1122 lacking sulfur and thence not able to release H₂S was inactive. Similar results were obtained using a clonogenic assay. Incubation of GYY4137 (400 µM in culture medium led to the generation of low (<20 µM concentrations of H₂S sustained over 7 days. In contrast, incubation of NaHS (400 µM in the same way led to much higher (up to 400 µM concentrations of H₂S which persisted for only 1 hour. Mechanistic studies revealed that GYY4137 (400 µM incubated for 5 days with MCF-7 but not IMR90 cells caused the generation of cleaved PARP and cleaved caspase 9, indicative of a pro-apoptotic effect. GYY4137 (but not ZYJ1122 also caused partial G₂/M arrest of these cells. Mice xenograft studies using HL-60 and MV4-11 cells showed that GYY4137 (100-300 mg/kg/day for 14 days significantly reduced tumor growth. We conclude that GYY4137 exhibits anti-cancer activity by releasing H₂S over a period of days. We also propose that a combination of apoptosis and cell cycle arrest contributes to this effect and that H₂S donors should be investigated further as potential anti-cancer agents.

  9. Anti-Cancer Effects of Protein Extracts from Calvatia lilacina, Pleurotus ostreatus and Volvariella volvacea

    Directory of Open Access Journals (Sweden)

    Jin-Yi Wu

    2011-01-01

    Full Text Available Calvatia lilacina (CL, Pleurotus ostreatus (PO and Volvariella volvacea (VV are widely distributed worldwide and commonly eaten as mushrooms. In this study, cell viabilities were evaluated for a human colorectal adenocarcinoma cell line (SW480 cells and a human monocytic leukemia cell line (THP-1 cells. Apoptotic mechanisms induced by the protein extracts of PO and VV were evaluated for SW480 cells. The viabilities of THP-1 and SW480 cells decreased in a concentration-dependent manner after 24 h of treatment with the protein extracts of CL, PO or VV. Apoptosis analysis revealed that the percentage of SW480 cells in the SubG1 phase (a marker of apoptosis was increased upon PO and VV protein-extract treatments, indicating that oligonucleosomal DNA fragmentation existed concomitantly with cellular death. The PO and VV protein extracts induced reactive oxygen species (ROS production, glutathione (GSH depletion and mitochondrial transmembrane potential (ΔΨm loss in SW480 cells. Pretreatment with N-acetylcysteine, GSH or cyclosporine A partially prevented the apoptosis induced by PO protein extracts, but not that induced by VV extracts, in SW480 cells. The protein extracts of CL, PO and VV exhibited therapeutic efficacy against human colorectal adenocarcinoma cells and human monocytic leukemia cells. The PO protein extracts induced apoptosis in SW480 cells partially through ROS production, GSH depletion and mitochondrial dysfunction. Therefore, the protein extracts of these mushrooms could be considered an important source of new anti-cancer drugs.

  10. Anticancer Effects of 15d-Prostaglandin-J(2) in Wild-Type and Doxorubicin-Resistant Ovarian Cancer Cells : Novel Actions on SIRT1 and HDAC

    NARCIS (Netherlands)

    de Jong, Edwin; Winkel, Peter; Poelstra, Klaas; Prakash, Jai

    2011-01-01

    15-deoxy-delta-12,14-prostaglandin-J(2) (15d-PGJ(2)), an arachidonic metabolite and a natural PPAR gamma agonist, is known to induce apoptosis in tumor cells. In this study, we investigated new therapeutic potentials of 15d-PGJ(2) by determining its anticancer effects in wild-type and doxorubicin-re

  11. Anthocyanins extracted from Chinese blueberry (Vaccinium uliginosum L.) and its anticancer effects on DLD-1 and COLO205 cells

    Institute of Scientific and Technical Information of China (English)

    ZU Xiao-yan; ZHANG Zhen-ya; ZHANG Xiao-wen; YOSHIOKA Masahiro; YANG Ying-nan; LI Ji

    2010-01-01

    Background Vaccinium uliginosum L. is a type of blueberry found in the Chinese Changbai Mountains. We extracted Vaccinium uliginosurn Anthocyanins (Av.uli) to investigate its bioactivity on suppressing cancer cells.Methods Av.uli was extracted under different conditions of temperature (10℃-35℃), pH 1.0-3.0, and diatomaceous earth (1.0 g-3.0 g), followed by a HPLC analysis for the determination of the ingredients. Its anticancer bioactivities on human colon and colorectal cancer cells (DLD-1 and COLO205) were compared with those on Lonicera caerulea Anthocyanins (AL.cae) and Vaccinium myrtillus Anthocyanins (Av.myr), using cell viability assays, DNA electrophoresis and nuclear morphology assays.Results The optimum process of Av.uliextraction involved conditions of temperature 20℃, pH 2.0, and diatomaceous earth 1.0 g/50 g of fruit weight. Av.uli contained 5 main components: delphinidin (40.70±1.72)%, cyanidin (3.40±0.68)%,petunidin (17.70±0.54)%, peonidin (2.90±0.63)% and malvidin (35.50±1.11)%. The malvidin percentage was significantly higher (P <0.05) than it in Av.myr. Av.uli complied with a dose-dependent repression of cancer cell proliferation with an IC50 (50% inhibitory concentration) value of 50 μg/ml, and showed greater anticancer efficiency than AL. cae and Av. myr under the same cell treatment conditions. These observations were further supported by the results of nuclear assays.Conclusions The extraction protocol and conditions we used were effective for anthocyanin extraction. Av.uli could be a feasible practical research tool and a promising therapeutic source to suppress human colon or colorectal cancers.

  12. Pig fatness in relation to FASN and INSIG2 genes polymorphism and their transcript level.

    Science.gov (United States)

    Grzes, Maria; Sadkowski, Slawomir; Rzewuska, Katarzyna; Szydlowski, Maciej; Switonski, Marek

    2016-05-01

    Fat content and fatty acid (FA) profile influence meat quality in pigs. These parameters are important for consumers due to their preferences for healthy, high quality meat. The aim of this study was searching for polymorphisms and transcript levels of two positional and functional candidate genes, FASN and INSIG2, encoding proteins which take part in lipid metabolism. The molecular findings were analyzed in relation to fatness traits. Pigs of four commercial breeds were included: Polish Landrace (PL), Polish Large White (PLW), Duroc and Pietrain. DNA sequencing, 5'RACE technique and real time PCR and association analysis were applied. In total, 20 polymorphisms in 5'-flanking, 5'UTR and 3'UTR regions of FASN (12 novel polymorphisms) and INSIG2 (seven novel ones and one known) genes were found. Association study with fatness traits (PL n = 225, PLW n = 179) revealed that four polymorphisms (c.-2908G>A, c.-2335C>T, c.*42_43insCCCCA and c.*264A>G) of the FASN gene were associated with back fat thickness in PL and PLW. Since the polymorphisms were identified in regulatory sequences of the both genes also their transcript levels were studied in PLW (n = 23), PL (n = 22), Pietrain (n = 17) and Duroc (n = 23). The INSIG2 transcript level was positively correlated with monounsaturated FA contents in the longissimus thoracis et lumborum muscle. Several correlations were also found between three polymorphisms (c.*264A>G and c.-2335C>T in FASN, and c.-5527C>G in INSIG2) and the FA content. Our study showed that the FASN gene is a promising marker for subcutaneous fat tissue accumulation, while INSIG2 is a promising marker for FA composition. PMID:26965892

  13. Combinatorial effects of geopropolis produced by Melipona fasciculata Smith with anticancer drugs against human laryngeal epidermoid carcinoma (HEp-2) cells.

    Science.gov (United States)

    Bartolomeu, Ariane Rocha; Frión-Herrera, Yahima; da Silva, Livia Matsumoto; Romagnoli, Graziela Gorete; de Oliveira, Deilson Elgui; Sforcin, José Maurício

    2016-07-01

    The identification of natural products exerting a combined effect with therapeutic agents could be an alternative for cancer treatment, reducing the concentration of the drugs and side effects. Geopropolis (Geo) is produced by some stingless bees from a mixture of vegetable resins, gland secretions of the bees and soil. It has been used popularly as an antiseptic agent and to treat respiratory diseases and dermatosis. To determine whether Geo enhances the anticancer effect of carboplatin, methotrexate and doxorubicin (DOX), human laryngeal epidermoid carcinoma (HEp-2) cells were treated with Geo alone or in combination with each drug. Cell growth, cytotoxicity and apoptosis were evaluated using 3-(4,5-dimethyl thiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release, and flow cytometry. Scratch assay was used to analyze cell migration and transmission electron microscopy to observe morphologic alterations. The influence of Geo on drug resistance was also investigated assessing P-glycoprotein (P-gp) action. Geo inhibited cell proliferation and migration. The combination Geo+DOX led to the highest cytotoxic activity and induced apoptosis, leading to loss of membrane integrity. Geo had no effect on P-gp-mediated efflux of DOX. Data indicate that Geo combined with DOX could be a potential clinical chemotherapeutic approach for laryngeal cancer treatment. PMID:27261576

  14. Prolonged local persistence of cisplatin-loaded gelatin microspheres and their chemoembolic anti-cancer effect in rabbits

    International Nuclear Information System (INIS)

    Purpose: To confirm prolonged cisplatin release from drug-loaded gelatin microspheres (GMSs) and their improved chemoembolic anti-cancer effect against VX2 liver tumors in rabbits. Materials and methods: Two groups of twelve rabbits each were treated intraarterially either with 2 mg/kg cisplatin-loaded GMSs (=0.04 mg/kg cisplatin) or 0.04 mg/kg cisplatin solution by administering them into the right renal artery. Platinum concentrations within the renal parenchyma were analyzed immediately following infusion (day 0) and on days 1, 3, and 7 using the atomic absorption method. In a second experiment four groups of five rabbits each with implanted VX2 liver tumors were treated intraarterially through the hepatic artery with the following drugs: 2 mg/kg cisplatin-loaded GMSs (=0.04 mg/kg cisplatin) (group I), 2 mg/kg GMSs without any drug (group II), 1.5 mg/kg cisplatin solution (group III) and saline (group IV). Tumor volumes were analyzed pre-injection and 7 days after with MRI allowing calculating the relative tumor growth rate (%). Degree of liver cell necrosis was assessed on the histopathological specimens. Results: The renal parenchymal platinum concentrations (μg/ml) with 4.51 ± 2.25 (day 0), 1.59 ± 0.70 (day 1), 0.72 ± 0.10 (day 3) and 0.20 ± 0.06 (day 7) were significantly more pronounced after cisplatin-loaded GMS on days one and three compared to cisplatin with 1.99 ± 0.55, 0.08 ± 0.03, 0.18 ± 0.01 and 0.10 ± 0.07, respectively. Relative tumor growth rates resulted in 84.5% ± 26.4 (group I); 241.4% ± 145.1 (II); 331.9% ± 72.2 (III), and 413.6% ± 103.6 (IV) with statistical significant differences between groups I and III, and groups I and IV. Similar degrees of necrosis were observed in both GMSs treated groups, while ballooning of hepatocytes was highest in cisplatin-loaded GMSs. Conclusions: With cisplatin-loaded GMSs more pronounced and prolonged local parenchymal cisplatin concentrations may be achieved offering the advantage of an

  15. Interfacial Cohesion and Assembly of Bioadhesive Molecules for Design of Long-Term Stable Hydrophobic Nanodrugs toward Effective Anticancer Therapy.

    Science.gov (United States)

    Shen, Guizhi; Xing, Ruirui; Zhang, Ning; Chen, Chengjun; Ma, Guanghui; Yan, Xuehai

    2016-06-28

    The majority of anticancer drugs are poorly water-soluble and thus suffer from rather low bioavailability. Although a variety of delivery carriers have been developed for bioavailability improvement, they are severely limited by low drug loading and undesired side effects. The optimum delivery vehicle would be a biocompatible and biodegradable drug nanoparticle of uniform size with a thin but stable shell, making it soluble, preventing aggregation and enabling targeting. Here, we present a general strategy for the rational design of hydrophobic drug nanoparticles with high drug loading by means of interfacial cohesion and supramolecular assembly of bioadhesive species. We demonstrate that the pathway is capable of effectively suppressing and retarding Ostwald ripening, providing drug nanoparticles with small and uniform size and long-term colloidal stability. The final complex drug nanoparticles provide higher tumor accumulation, negligible toxicity, and enhanced antitumor activity, superior to commercial formulations. Our findings demonstrate that local, on-demand coating of hydrophobic nanoparticles is achievable through cooperation and compromise of interfacial adhesion and assembly. PMID:27223166

  16. Enhanced Bioavailability and Anticancer Effect of Curcumin-Loaded Electrospun Nanofiber: In Vitro and In Vivo Study

    Science.gov (United States)

    Wang, Chuan; Ma, Chao; Wu, Zhenkai; Liang, He; Yan, Peng; Song, Jia; Ma, Nan; Zhao, Qinghua

    2015-11-01

    Nanofibers have attracted increasing attention in drug delivery and other biomedical applications due to their some special properties. The present study aims to prepare a fiber-based nanosolid dispersion system to enhance the bioavailability of curcumin (CUR). CUR-loaded polyvinyl pyrrolidone (CUR@PVP) nanofibers were successfully prepared via electrospinning. Scanning electron microscopy (SEM) was employed to observe the morphology of the nanofibers, and the SEM image showed that the drug-loaded nanofibers were smooth, and no CUR clusters were found on the surface of the nanofibers. The results of X-ray diffraction (XRD) demonstrated that the CUR was evenly distributed in the nanofibers in an amorphous state. Fourier transform infrared (FTIR) spectroscopy analysis indicated that intermolecular hydrogen bonding occurred between the CUR and the polymer matrix. In vitro dissolution profiles showed that CUR@PVP nanofiber could be quickly dissolved in phosphate-buffered saline (PBS) solution, while negligible dissolution was observed in pure CUR sample. Importantly, in vitro cell viability assays and in vivo animal tests revealed that the nanosolid dispersion system dramatically enhanced the bioavailability and showed effective anticancer effect of the CUR.

  17. Studies on In Vitro Slow-Release Characteristics and Anticancer Effect of 5-Fluorouracil-Loaded Immuno-Nanoparticles

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    OBJECTIVE To investigate slow-release features of biodegradable anticancer 5-fluorouracil-loaded immunonanoparticles (5-FU INPs), and to assess their tumor cell killing activity in vitro.METHODS The method of vibrating dialysis at a constant temperature,and first-order derivative ultraviolet spectrophotometry were used to determine the drug-releasing character of 5-FU INPs. The methyl thiazolyl tetrazolium (MTT) colorimetric method was employed to assay the killing activity of 5-FU INPs on 5 tumor cell lines at different phases.RESULTS The 5-FU INPs had a favorable slow-release function, with a t1/2 release time of 10.4 days. The 5-FU INPs had a rather strong lethal effect on 5 tumor cell lines resulting in a positive correlativity between the killing activity and the action time and amount of the drug released.CONCLUSION The drug disposition is uniform from the 5-FU INPs,and there is no impact on efficacy of the 5-FU during preparation and degradation of the 5-FU INPs. The 5-FU INPs have a favorable function for drug release, and can maintain an effective killing activity over a long period of time.

  18. The Cost-Saving Effect of a Centralized Unit for Anticancer Drugs Processing at the Oncology Department of Tirana

    Directory of Open Access Journals (Sweden)

    Artan Shkoza

    2015-11-01

    Full Text Available The worldwide increase in cancer prevalence has led to a substantial cost rising in Medical Oncology. Of particular importance are highly expensive drugs used to treat various types of cancers in developing countries like Albania. Hence, pharmacoeconomics may play an important role in reducing the drug wastage and financial burden placed on patients, family and society in general; of course, without adversely impacting patient’s health outcomes. Our aim was to calculate cost-savings effect of a centralized unit, which allows residual amounts of unused drugs to be reused by patients whose treatments are elaborated in the same working day. We calculated in a comprehensive manner the number of saved vials (flasks for seven drugs generated from residual amounts of the same working day and, converted them into cost-saving monetary value. We did not take into account prescribed drug dosages that fitted exactly with doses contained in a vial. Over a six month period, there were: a total of 6558 prescriptions for a total of 1180 patients, a total of 1524 saved vials and, a total cost-saving of 134, 348 (•. The saved value represents 6.2 percent of the cytostatic drugs budget for 2005. Our experience confirms the economic benefit of waste reduction and cost-savings effect due to a centralized unit of anticancer drug processing. The centralized unit increases also the drug traceability from preparation to patient.

  19. Anticancer chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Weller, R.E.

    1991-10-01

    This document examines chemotherapeutic agents for use in veterinary oncology. It lists some of the most common categories of chemotherapeutic drugs, such as alkylating agents and corticosteroids. For each category, the paper lists some example drugs, gives their mode of action, tumors usually susceptible to the drug, and common side effects. A brief discussion of mechanisms of drug resistance is also provided. (MHB)

  20. In situ synthesized BSA capped gold nanoparticles: Effective carrier of anticancer drug Methotrexate to MCF-7 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Murawala, Priyanka [Physical and Materials Chemistry Division, National Chemical Laboratory, Pune 411008 (India); Tirmale, Amruta [Physical and Materials Chemistry Division, National Chemical Laboratory, Pune 411008 (India); National Centre for Cell Science, NCCS, Pune 411007 (India); Shiras, Anjali, E-mail: anjalishiras@nccs.res.in [National Centre for Cell Science, NCCS, Pune 411007 (India); Prasad, B.L.V., E-mail: pl.bhagavatula@ncl.res.in [Physical and Materials Chemistry Division, National Chemical Laboratory, Pune 411008 (India)

    2014-01-01

    The proficiency of MTX loaded BSA capped gold nanoparticles (Au-BSA-MTX) in inhibiting the proliferation of breast cancer cells MCF-7 as compared to the free drug Methotrexate (MTX) is demonstrated based on MTT and Ki-67 proliferation assays. In addition, DNA ladder gel electrophoresis studies, flow cytometry and TUNEL assay confirmed the induction of apoptosis by MTX and Au-BSA-MTX in MCF-7 cells. Notably, Au-BSA-MTX was found to have higher cytotoxicity on MCF-7 cells compared with an equivalent dose of free MTX. The enhanced activity is attributed to the preferential uptake of Au-BSA-MTX particles by MCF-7 cells due to the presence of BSA that acts as a source of nutrient and energy to the rapidly proliferating MCF-7 cells. Moreover, the targeting ability of the drug MTX to the over expressed folate receptors on MCF-7 cells also contributes to the enhanced uptake and activity. Taken together, these results unveil that Au-BSA-MTX could be more effective than free drug for cancer treatment. - Highlights: • Gold nanoparticles prepared using bovine serum albumin as a reducing and capping agent. • These gold nanoparticles are extremely stable under strong electrolyte and pH conditions. • The anticancer drug methotrexate has been loaded on the Au-BSA nanoparticles. • Due to BSA loading these are taken up by cancerous cells preferentially. • Better proficiency in inhibiting MCF-7 cells as compared to the free drug Methotrexate is demonstrated.

  1. In situ cultured preantral follicles is a useful model to evaluate the effect of anticancer drugs on caprine folliculogenesis.

    Science.gov (United States)

    Guerreiro, Denise Damasceno; Lima, Laritza Ferreira de; Rodrigues, Giovanna Quintino; Carvalho, Adeline de Andrade; Castro, Simone Vieira; Campello, Cláudio Cabral; Pessoa, Cláudia do Ó; Gadelha, Carla Renata Figueiredo; Figueiredo, José Ricardo de; Bordignon, Vilceu; Rodrigues, Ana Paula Ribeiro

    2016-08-01

    Despite the increase in the incidence of cancer, the number of women who survive cancer treatment is growing. However, one of the principal results of chemotherapy is premature ovarian failure (POF). The aim of this study was to use the in situ culture preantral follicles as an in vitro model to evaluate the toxicity of two anticancer drugs, doxorubicin (DXR) and paclitaxel (PTX), on the integrity and development of ovarian follicles. Fragments of the ovarian cortex of goats were cultured in vitro for 1 or 7 days in α-MEM(+) supplemented with different concentrations of DXR (0.003, 0.03, or 0.3 µg/mL) and PTX (0.001, 0.01, or 0.1 µg/mL). Analyses were performed before and after culture to evaluate tissue integrity by classical histology, apoptosis by TUNEL assay, DNA laddering kit and the detection of activated caspase 3, and DNA damage by the immune detection of phosphorylated histone H2A.x (H2AXph139). Both DXR and PTX reduced the number of morphologically normal primordial and developing follicles. Positive staining for TUNEL and active caspase 3 was detected in all the samples (P < 0.05). Therefore, we propose the in situ culture of caprine preantral follicles as a useful experimental model for assessing the toxic effects of the chemotherapeutic agents on ovarian folliculogenesis. Microsc. Res. Tech. 79:773-781, 2016. © 2016 Wiley Periodicals, Inc. PMID:27311936

  2. In situ synthesized BSA capped gold nanoparticles: Effective carrier of anticancer drug Methotrexate to MCF-7 breast cancer cells

    International Nuclear Information System (INIS)

    The proficiency of MTX loaded BSA capped gold nanoparticles (Au-BSA-MTX) in inhibiting the proliferation of breast cancer cells MCF-7 as compared to the free drug Methotrexate (MTX) is demonstrated based on MTT and Ki-67 proliferation assays. In addition, DNA ladder gel electrophoresis studies, flow cytometry and TUNEL assay confirmed the induction of apoptosis by MTX and Au-BSA-MTX in MCF-7 cells. Notably, Au-BSA-MTX was found to have higher cytotoxicity on MCF-7 cells compared with an equivalent dose of free MTX. The enhanced activity is attributed to the preferential uptake of Au-BSA-MTX particles by MCF-7 cells due to the presence of BSA that acts as a source of nutrient and energy to the rapidly proliferating MCF-7 cells. Moreover, the targeting ability of the drug MTX to the over expressed folate receptors on MCF-7 cells also contributes to the enhanced uptake and activity. Taken together, these results unveil that Au-BSA-MTX could be more effective than free drug for cancer treatment. - Highlights: • Gold nanoparticles prepared using bovine serum albumin as a reducing and capping agent. • These gold nanoparticles are extremely stable under strong electrolyte and pH conditions. • The anticancer drug methotrexate has been loaded on the Au-BSA nanoparticles. • Due to BSA loading these are taken up by cancerous cells preferentially. • Better proficiency in inhibiting MCF-7 cells as compared to the free drug Methotrexate is demonstrated

  3. Effect of chromium on antioxidant potential of Catharanthus roseus varieties and production of their anticancer alkaloids: vincristine and vinblastine.

    Science.gov (United States)

    Rai, Vartika; Tandon, Pramod Kumar; Khatoon, Sayyada

    2014-01-01

    Catharanthus roseus (L.) G. Don, a medicinal plant, has a very important place in the traditional as well as modern pharmaceutical industry. Two common varieties of this plant rosea and alba are named so because of pink and white coloured flowers, respectively. This plant comprises of about 130 terpenoid indole alkaloids and two of them, vincristine and vinblastine, are common anticancer drugs. The effect of chromium (Cr) on enzymatic and non-enzymatic antioxidant components and on secondary metabolites vincristine and vinblastine was studied under pot culture conditions of both varieties of C. roseus. Antioxidant responses of these varieties were analyzed under 0, 10, 50, and 100  μM chromium (Cr) level in order to investigate the plant's protective mechanisms against Cr induced oxidative stress. The results indicated that Cr affects all the studied parameters and decreases growth performance. However, vincristine and vinblastine contents were increased under Cr stress. Results are quite encouraging, as this plant shows good antioxidant potential and increased the level of active constituents under Cr stress. PMID:24734252

  4. Effect of Chromium on Antioxidant Potential of Catharanthus roseus Varieties and Production of Their Anticancer Alkaloids: Vincristine and Vinblastine

    Directory of Open Access Journals (Sweden)

    Vartika Rai

    2014-01-01

    Full Text Available Catharanthus roseus (L. G. Don, a medicinal plant, has a very important place in the traditional as well as modern pharmaceutical industry. Two common varieties of this plant rosea and alba are named so because of pink and white coloured flowers, respectively. This plant comprises of about 130 terpenoid indole alkaloids and two of them, vincristine and vinblastine, are common anticancer drugs. The effect of chromium (Cr on enzymatic and non-enzymatic antioxidant components and on secondary metabolites vincristine and vinblastine was studied under pot culture conditions of both varieties of C. roseus. Antioxidant responses of these varieties were analyzed under 0, 10, 50, and 100 μM chromium (Cr level in order to investigate the plant’s protective mechanisms against Cr induced oxidative stress. The results indicated that Cr affects all the studied parameters and decreases growth performance. However, vincristine and vinblastine contents were increased under Cr stress. Results are quite encouraging, as this plant shows good antioxidant potential and increased the level of active constituents under Cr stress.

  5. Promising anticancer activity of a lichen, Parmelia sulcata Taylor, against breast cancer cell lines and genotoxic effect on human lymphocytes.

    Science.gov (United States)

    Ari, Ferda; Ulukaya, Engin; Oran, Seyhan; Celikler, Serap; Ozturk, Sule; Ozel, Mustafa Zafer

    2015-05-01

    Plants are still to be explored for new anti-cancer compounds because overall success in cancer treatment is still not satisfactory. As a new possible source for such compounds, the lichens are recently taking a great attention. We, therefore, explored both the genotoxic and anti-growth properties of lichen species Parmelia sulcata Taylor. The chemical composition of P. sulcata was analyzed with comprehensive gas chromatography-time of flight mass spectrometry. Anti-growth effect was tested in human breast cancer cell lines (MCF-7 and MDA-MB-231) by the MTT and ATP viability assays, while the genotoxic activity was studied by assays for micronucleus, chromosomal aberration and DNA fragmentation in human lymphocytes culture. Cell death modes (apoptosis/necrosis) were morphologically assessed. P. sulcata inhibited the growth in a dose-dependent manner up to a dose of 100 μg/ml and induced caspase-independent apoptosis. It also showed genotoxic activity at doses (>125 μg/ml) higher than that required for apoptosis. These results suggest that P. sulcata may induce caspase-independent apoptotic cell death at lower doses, while it may be genotoxic at relatively higher doses. PMID:24676908

  6. Cyclooxygenase/lipoxygenase shunting lowers the anti-cancer effect of cyclooxygenase-2 inhibition in colorectal cancer cells

    Directory of Open Access Journals (Sweden)

    Ganesh Radhakrishnan

    2012-09-01

    Full Text Available Abstract Background Arachidonic acid metabolite, generated by cyclooxygenase (COX, is implicated in the colorectal cancer (CRC pathogenesis. Inhibiting COX may therefore have anti-carcinogenic effects. Results from use of non-steroidal anti-inflammatory drugs inhibiting only COX have been conflicting. It has been postulated that this might result from the shunting of arachidonic acid metabolism to the 5-lipoxygenase (5-LOX pathway. Cancer cell viability is promoted by 5-LOX through several mechanisms that are similar to those of cyclooxygenase-2 (COX-2. Expression of 5-LOX is upregulated in colorectal adenoma and cancer. The aim of this study was to investigate the shunting of arachidonic acid metabolism to the 5-LOX pathway by cyclooxygenase inhibition and to determine if this process antagonizes the anti-cancer effect in colorectal cancer cells. Methods Three colorectal cancer cell lines (HCA7, HT-29 & LoVo expressing 5-LOX and different levels of COX-2 expression were used. The effects of aspirin (a non-selective COX inhibitor and rofecoxib (COX-2 selective on prostaglandin E2 (PGE2 and leukotriene B4 (LTB4 secretion were quantified by ELISA. Proliferation and viability were studied by quantifying double-stranded DNA (dsDNA content and metabolic activity. Apoptosis was determined by annexin V and propidium iodide staining using confocal microscopy, and caspase-3/7 activity by fluorescent substrate assay. Results COX inhibitors suppressed PGE2 production but enhanced LTB4 secretion in COX-2 expressing cell lines (P  Conclusions This study provides evidence of shunting between COX and 5-LOX pathways in the presence of unilateral inhibition, and may explain the conflicting anti-carcinogenic effects reported with use of COX inhibitors.

  7. Ginseng Extract Enhances Anti-cancer Effect of Cytarabine on Human Acute Leukemia Cells

    OpenAIRE

    Yiju Hou; Xiaodong Liu; Zhonghai Yuan; Yan Li

    2015-01-01

    Ginseng as a traditional medicine is well known to exhibit various pharmacological effects. Ginsenoside Rg3 is the active ingredient extracted from ginseng. The pharmacological modulatory effects of Rg3 on multidrug resistant cancer cells are reported in the present study. Cytarabine is a chemotherapeutic agent for the treatment of acute leukemia. However, this compound has serious side effects at high doses, for example hematopoiesis depression. In this study, using hl60 human leukemia cells...

  8. Anti-cancer and anti-angiogenic effects of curcumin and tetrahydrocurcumin on implanted hepatocellular carcinoma in nude mice

    Institute of Scientific and Technical Information of China (English)

    Pornprom Yoysungnoen; Ponthip Wirachwong; Chatchawan Changtam; Apichart Suksamrarn; Suthiluk Patumraj

    2008-01-01

    AIM: To determine the effect of tetrahydrocurcumin (THC) on tumor angiogenesis compared with curcumin (CUR) by using both in vitro and in vivo models of human hepatocellular carcinoma cell line (HepG2).METHODS: The 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay was used for testing the anti-proliferating activities of CUR and THC. In male BALB/c nude mice, 2 x 106 human HepG2 cells were inoculated onto a dorsal skin-fold chamber. One day after HepG2 inoculation, the experimental groups were fed oral daily with CUR or THC (300 mg/kg or 3000 mg/kg). On d 7, 14 and 21, the tumor microvasculature was observed using fluorescence videomicroscopy and capillary vascularity (CV) was measured.RESULTS: Pathological angiogenic features including microvascular dilatation, tortuosity, and hyper-permeability were observed. CUR and THC could attenuate these pathologic features. In HepG2-groups, the CV were significantly increased on d 7 (52.43%), 14 (69.17%), and 21 (74.08%), as compared to controls (33.04%,P < 0.001). Treatment with CUR and THC resulted in significant decrease in the CV (P < 0.005 and P < 0.001, respectively). In particular, the anti-angiogenic effects of CUR and THC were dose-dependent manner. However, the beneficial effect of THC treatment than CUR was observed, in particular, from the 21 d CV (44.96% and 52.86%, P < 0.05).CONCLUSION: THC expressed its anti-angiogenesis without any cytotoxic activities to HepG2 cells even at the highest doses. It is suggested that anti-angiogenic properties of CUR and THC represent a common potential mechanism for their anti-cancer actions.

  9. Enhanced targeted anticancer effects and inhibition of tumor metastasis by the TMTP1 compound peptide TMTP1-TAT-NBD.

    Science.gov (United States)

    Liu, Ronghua; Xi, Ling; Luo, Danfeng; Ma, Xiangyi; Yang, Wanhua; Xi, Yandong; Wang, Hongyan; Qian, Ming; Fan, Liangsheng; Xia, Xi; Li, Kezheng; Wang, Daowen; Zhou, Jianfeng; Meng, Li; Wang, Shixuan; Ma, Ding

    2012-08-10

    Micromolecular agents that block tumor development and metastasis hold great promise as cancer-targeted therapies. Tumor molecular targeted peptide 1 (TMTP1) was previously shown to target primary tumors and metastatic foci specifically. In this study, a group of composite peptides were incorporated to TMPT1. The NF-κB essential modulator-binding domain (NBD), and the trans-activator of transcription (TAT) peptide, were synthesized to enhance the targeted anti-tumor effects of TMTP1. TMTP1-NBD did not exhibit strong affinity to tumor cells as we had expected. Conjugating TAT with TMTP1-NBD ameliorated the poor hydrophilicity and negative charge of TMTP1-NBD. Therefore TMTP1-TAT-NBD displayed strong affinity and anti-tumor effects as we expected in vivo and in vitro. Interestingly cytoplasmic glycogen accumulation as well as apoptosis was observed in TMTP1-TAT-NBD treated PC-3M-1E8 cells. The downstream signaling pathways including AKT, GSK-3β, IκBα and NF-κB activity were verified to decrease by TMTP1-TAT-NBD. The pharmacokinetics and distribution of TMTP1-TAT-NBD in MDA-MB-231 tumor-bearing mice model provided some evidence for safety of the composite peptide, which showed the fluorescence of the peptide peaked in the tumor 6h after injection, with little fluorescence detected in normal organs except for very weak fluorescence in kidney. In conclusion, TMTP1-TAT-NBD may be a promising targeted anti-tumor agent for primary tumor and metastatic foci, which enhances the anticancer effects through inhibiting the AKT/GSK-3β/NF-κB pathway comparing with TMTP1. PMID:22580115

  10. The anti-cancer effect of Propranolol in K562 cell line: an in vitro study

    Directory of Open Access Journals (Sweden)

    S Bastani

    2016-03-01

    Full Text Available Introduction: Β-AR receptors are one of the proteins involved in cancer and stress. The therapeutic activity of β-blockers such as propranolol is attributed to the blockade of β1-adrenergic receptors (ARs. In this study, the effect of propranolol on the viability of K562 cell line was examined. Material and methods: In order to assessment of anti-tumoral effects of propranolol, different concentrations of propranolol were prepared. K562 cells were treated with different concentrations of propranolol, then the percentage of inhibitory effect of propranolol on K562 cell viability at different times (24, 48 and 72 hours was estimated by MTT assay. Gel electrophoresis of DNA and DAPI staining were used for apoptosis investigation. Statistical comparisons were performed using two-sample t-test, Nominal significance level of each univariate test was 0.05. Results: Propranolol decreased viability of K562 cell line. The inhibitory effect of propranolol is time- and concentration-dependent, thus in higher concentrations and 72 hours after treatment, the maximum inhibitory effect was observed. (P<0.05. As the results showed, Propranolol induces apoptosis in K562 cell line. Conclusions: With respect to the inhibitory effect of propranolol on cell viability and its apoptotic effect on K562 cell line, this drug may be used for cancer therapy.

  11. Cost Effectiveness of Integrated Medicine in Patients With Cancer Receiving Anticancer Chemotherapy

    OpenAIRE

    Coriat, Romain; Boudou-Rouquette, Pascaline; Durand, Jean-Philippe; Forgeot d'Arc, Priscille; Martin, Idalie; Mir, Olivier; Ropert, Stanislas; Alexandre, Jérôme; Goldwasser, François

    2012-01-01

    The hospital-home monitoring program is a cost-effective strategy for offering ambulatory chemotherapy treatment to patients with cancer and has become the authors' standard procedure for ambulatory chemotherapy.

  12. Self-Targeted, Shape-Assisted, and Controlled-Release Self-Delivery Nanodrug for Synergistic Targeting/Anticancer Effect of Cytoplasm and Nucleus of Cancer Cells.

    Science.gov (United States)

    Li, Yang; Lin, Jinyan; Huang, Yu; Li, Yanxiu; Yang, Xiangrui; Wu, Hongjie; Wu, Shichao; Xie, Liya; Dai, Lizong; Hou, Zhenqing

    2015-11-25

    We constructed 10-hydroxycamptothecin (CPT) "nanodrugs" with functionalization of lipid-PEG-methotrexate (MTX) to prepare high-drug-loaded, and sustained/controlled-release MTX-PEG-CPT nanorods (NRs), in which MTX drug itself can serve as a specific "targeting ligand". The self-targeted nanodrug can codeliver both CPT and MTX drugs with distinct anticancer mechanisms. Furthermore, MTX-PEG-CPT NRs significantly reduced burst release, improved blood circulation and tumor accumulation, enhanced cellular uptake, and synergistically increased anticancer effect against tumor cells compared with MTX-PEG-CPT nanospheres (NSs) and either both free drugs or individual free drug. Therefore, the synergistic targeting/therapeuticy nano-multi-drug codelivery assisted by shape design may advantageously offer a promising new strategy for nanomedicine. PMID:26529185

  13. Data of a fluorescent imaging-based analysis of anti-cancer drug effects on three-dimensional cultures of breast cancer cells

    Directory of Open Access Journals (Sweden)

    Junji Itou

    2015-12-01

    Full Text Available Three-dimensional (3D cell culture is a powerful tool to study cell growth under 3D condition. To perform a simple test for anti-cancer drugs in 3D culture, visualization of non-proliferated cells is required. We propose a fluorescent imaging-based assay to analyze cancer cell proliferation in 3D culture. We used a pulse-labeling technique with a photoconvertible fluorescent protein Kaede to identify non-proliferated cells. This assay allows us to observe change in cell proliferation in 3D culture by simple imaging. Using this assay, we obtained the data of the effects of anti-cancer drugs, 5-fluorouracil and PD0332991 in a breast cancer cell line, MCF-7.

  14. 13,14-Dihydroxy groups are critical for the anti-cancer effects of garcinol.

    Science.gov (United States)

    Han, Chao-Ming; Zhou, Xin-Ying; Cao, Jing; Zhang, Xin-Yan; Chen, Xin

    2015-06-01

    In the presence of K2CO3/Cs2CO3 (molar ratio 10:1), garcinol was subjected to methylation by reaction with iodomethane at room temperature to afford 13,14-dimethoxy garcinol. The methylated garcinol derivative was screened against oral cancer cell line SCC15 for cell proliferation and apoptosis. 13,14-Dimethoxy garcinol showed weaker inhibitory activity on SCC15 cell growth than garcinol, and had little effect on cell cycle and apoptosis of SCC15, whereas garcinol effectively induced cell cycle arrest and cell apoptosis. Meanwhile, the ELISA data showed that the inhibitory effect of garcinol on 5-Lox pathway was more potent than 13,14-dimethoxy garcinol (Pgarcinol. PMID:26000492

  15. Anticancer effects of fraction isolated from fruiting bodies of Chaga medicinal mushroom, Inonotus obliquus (Pers.:Fr.) Pilát (Aphyllophoromycetideae): in vitro studies.

    Science.gov (United States)

    Lemieszek, Marta Kinga; Langner, Ewa; Kaczor, Józef; Kandefer-Szerszeń, Martyna; Sanecka, Bozena; Mazurkiewicz, Witold; Rzeski, Wojciech

    2011-01-01

    The medicinal mushroom Chaga, Inonotus obliquus (Pers.:Fr.) Pilát (Hymenochaetaceae), has been used in folk medicine in Russia, Poland, and most of the Baltic countries, as a cleansing and disinfecting measure, and as decoctions for stomach diseases, intestinal worms, liver and heart ailments, and cancer treatment. Many reports have been published concerning the health promoting functions of this mushroom, including antibacterial, hepatoprotective, anti-inflammatory, antitumor, and antioxidant activities. The purpose of the present study was evaluation of in vitro anticancer activity of fraction IO4 isolated from I. obliquus. The effect on cell proliferation, motility and viability was assessed in a range of cancer and normal cells. Chaga fraction prepared from dried fruiting bodies was subjected to anticancer evaluation in human lung carcinoma (A549), colon adenocarcinoma (HT-29), and rat glioma (C6) cell cultures. Human skin fibroblasts (HSF), bovine aorta endothelial cells (BAEC), models of rat oligodendrocytes (OLN-93), hepatocytes (Fao), rat astroglia, and mouse neurons (P19) were applied to test toxicity in normal cells. The following methods were applied: tumor cell proliferation (MTT assay and BrdU assay), cytotoxicity (LDH assay), tumor cell motility (wound assay), tumor cell morphology (May-Grünwald-Giemsa staining), and death detection (ELISA). Chaga fraction elicited anticancer effects which were attributed to decreased tumor cell proliferation, motility and morphological changes induction. Of note is the fact that it produced no or low toxicity in tested normal cells. The data presented could open interesting paths for further investigations of fraction IO4 as a potential anticancer agent. PMID:22135889

  16. Berberine sensitizes mutliple human cancer cells to the anticancer effects of doxorubicin in vitro

    OpenAIRE

    TONG, NANNAN; Jie ZHANG; CHEN, YOURAN; LI, ZHUBO; LUO, YONGHUANG; Zuo, Hua; Zhao, Xiaoyan

    2012-01-01

    The clinical use of doxorubicin (DOX), a potent antineoplastic agent, is limited by its serious side-effects, which include acute and chronic cumulative dose-related cardiotoxicity. Berberine (BER), a botanical alkaloid, has been reported to possess cardioprotective and antitumor effects. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-tetrazolium bromide (MTT) assay was used to detect the cell viability of A549, HeLa and HepG2 cells after each cell line was treated with DOX, BER or a combina...

  17. Anticancer activity of Amauroderma rude.

    Directory of Open Access Journals (Sweden)

    Chunwei Jiao

    Full Text Available More and more medicinal mushrooms have been widely used as a miraculous herb for health promotion, especially by cancer patients. Here we report screening thirteen mushrooms for anti-cancer cell activities in eleven different cell lines. Of the herbal products tested, we found that the extract of Amauroderma rude exerted the highest activity in killing most of these cancer cell lines. Amauroderma rude is a fungus belonging to the Ganodermataceae family. The Amauroderma genus contains approximately 30 species widespread throughout the tropical areas. Since the biological function of Amauroderma rude is unknown, we examined its anti-cancer effect on breast carcinoma cell lines. We compared the anti-cancer activity of Amauroderma rude and Ganoderma lucidum, the most well-known medicinal mushrooms with anti-cancer activity and found that Amauroderma rude had significantly higher activity in killing cancer cells than Ganoderma lucidum. We then examined the effect of Amauroderma rude on breast cancer cells and found that at low concentrations, Amauroderma rude could inhibit cancer cell survival and induce apoptosis. Treated cancer cells also formed fewer and smaller colonies than the untreated cells. When nude mice bearing tumors were injected with Amauroderma rude extract, the tumors grew at a slower rate than the control. Examination of these tumors revealed extensive cell death, decreased proliferation rate as stained by Ki67, and increased apoptosis as stained by TUNEL. Suppression of c-myc expression appeared to be associated with these effects. Taken together, Amauroderma rude represented a powerful medicinal mushroom with anti-cancer activities.

  18. Anticancer activity of Amauroderma rude.

    Science.gov (United States)

    Jiao, Chunwei; Xie, Yi-Zhen; Yang, Xiangling; Li, Haoran; Li, Xiang-Min; Pan, Hong-Hui; Cai, Mian-Hua; Zhong, Hua-Mei; Yang, Burton B

    2013-01-01

    More and more medicinal mushrooms have been widely used as a miraculous herb for health promotion, especially by cancer patients. Here we report screening thirteen mushrooms for anti-cancer cell activities in eleven different cell lines. Of the herbal products tested, we found that the extract of Amauroderma rude exerted the highest activity in killing most of these cancer cell lines. Amauroderma rude is a fungus belonging to the Ganodermataceae family. The Amauroderma genus contains approximately 30 species widespread throughout the tropical areas. Since the biological function of Amauroderma rude is unknown, we examined its anti-cancer effect on breast carcinoma cell lines. We compared the anti-cancer activity of Amauroderma rude and Ganoderma lucidum, the most well-known medicinal mushrooms with anti-cancer activity and found that Amauroderma rude had significantly higher activity in killing cancer cells than Ganoderma lucidum. We then examined the effect of Amauroderma rude on breast cancer cells and found that at low concentrations, Amauroderma rude could inhibit cancer cell survival and induce apoptosis. Treated cancer cells also formed fewer and smaller colonies than the untreated cells. When nude mice bearing tumors were injected with Amauroderma rude extract, the tumors grew at a slower rate than the control. Examination of these tumors revealed extensive cell death, decreased proliferation rate as stained by Ki67, and increased apoptosis as stained by TUNEL. Suppression of c-myc expression appeared to be associated with these effects. Taken together, Amauroderma rude represented a powerful medicinal mushroom with anti-cancer activities. PMID:23840494

  19. Effects of Complementary and Alternative Medicines (CAM) on the Metabolism and Transport of Anticancer Drugs

    NARCIS (Netherlands)

    Mooiman, K.D.

    2013-01-01

    The use of complementary and alternative medicines (CAM), such as herbs and dietary supplements, has become more popular among cancer patients. Cancer patients use these supplements for different reasons such as reduction of side effects and improvement of their quality of life. In general, the use

  20. Anticancer effects of geopropolis produced by stingless bees on canine osteosarcoma cells in vitro.

    Science.gov (United States)

    Cinegaglia, Naiara Costa; Bersano, Paulo Ricardo Oliveira; Araújo, Maria José Abigail Mendes; Búfalo, Michelle Cristiane; Sforcin, José Maurício

    2013-01-01

    Geopropolis is produced by indigenous stingless bees from the resinous material of plants, adding soil or clay. Its biological properties have not been investigated, such as propolis, and herein its cytotoxic action on canine osteosarcoma (OSA) cells was evaluated. OSA is a primary bone neoplasm diagnosed in dogs being an excellent model in vivo to study human OSA. spOS-2 primary cultures were isolated from the tumor of a dog with osteosarcoma and incubated with geopropolis, 70% ethanol (geopropolis solvent), and carboplatin after 6, 24, 48, and 72 hours. Cell viability was analyzed by the crystal violet method. Geopropolis was efficient against canine OSA cells in a dose- and time-dependent way, leading to a distinct morphology compared to control. Geopropolis cytotoxic action was exclusively due to its constituents since 70% ethanol (its solvent) had no effect on cell viability. Carboplatin had no effect on OSA cells. Geopropolis exerted a cytotoxic effect on canine osteosarcoma, and its introduction as a possible therapeutic agent in vivo could be investigated, providing a new contribution to OSA treatment. PMID:23690851

  1. Potent anti-cancer effect of 3'-hydroxypterostilbene in human colon xenograft tumors.

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    Tzu-Chun Cheng

    Full Text Available Here we report that 3'-hydroxypterostilbene (HPSB, a natural pterostilbene analogue, was more potent than pterostilbene against the growth of human cancer cells (COLO 205, HCT-116, and HT-29 with measured IC50 values of 9.0, 40.2, and 70.9 µM, respectively. We found that HPSB effectively inhibited the growth of human colon cancer cells by inducing apoptosis and autophagy. Autophagy occurred at an early stage and was observed through the formation of acidic vesicular organelles and microtubule-associated protein 1 light chain 3-II production. At the molecular levels, the results from western blot analysis showed that HPSB significantly down-regulated phosphatidylinositol 3-kinase (PI3K/Akt and mitogen-activated protein kinases (MAPKs signalings including decreased the phosphorylation of mammalian target of rapamycin (mTOR. Significant therapeutic effects were demonstrated in vivo by treating nude mice bearing COLO 205 tumor xenografts with HPSB (10 mg/kg i.p.. These inhibitory effects were accompanied by mechanistic down-regulation of the protein levels of cyclooxygenase-2 (COX-2, matrix metallopeptidase-9 (MMP-9, vascular endothelial growth factor (VEGF, and cyclin D1, as well as by the induction of apoptosis in colon tumors. Our findings suggest that HPSB could serve as a novel promising agent for colon cancer treatment.

  2. Anticancer effect of the extracts from Polyalthia evecta against human hepatoma cell line (HepG2)

    Institute of Scientific and Technical Information of China (English)

    Sasipawan Machana; Natthida Weerapreeyakul; Sahapat Barusrux

    2012-01-01

    Objective: To investigate the anticancer activity of Polyalthia evecta (P. evecta) (Pierre) Finet& Gagnep against human hepatoma cell line (HepG2). Methods: The anticancer activity was based on (a) the cytotoxicity against human hepatoma cells (HepG2) assessed using a neutral red assay and (b) apoptosis induction determined by evaluation of nuclei morphological changes after DAPI staining. Preliminary phytochemical analysis of the crude extract was assessed by HPLC analysis. Results: The 50% ethanol-water crude leaf extract of P. evecta (EW-L) showed greater potential anticancer activity with high cytotoxicity [IC50 = (62.8 ± 7.3)μg/mL] and higher selectivity in HepG2 cells than normal Vero cells [selective index (SI) = 7.9]. The SI of EW-L was higher than the positive control, melphalan (SI = 1.6) and the apoptotic cells (46.4 ± 2.6) % induced by EW-L was higher than the melphalan (41.6 ± 2.1)% (P<0.05). The HPLC chromatogram of the EW-L revealed the presence of various kinds of polyphenolics and flavonoids in it. Conclusions:P. evecta is a potential plant with anticancer activity. The isolation of pure compounds and determination of the bioactivity of individual compounds will be further performed.

  3. Structural and dynamical effects induced by the anticancer drug topotecan on the human topoisomerase I - DNA complex.

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    Giordano Mancini

    Full Text Available BACKGROUND: Human topoisomerase I catalyzes the relaxation of DNA supercoils in fundamental cell processes like transcription, replication and chromosomal segregation. It is the only target of the camptothecin family of anticancer drugs. Among these, topotecan has been used to treat lung and ovarian carcinoma for several years. Camptothecins reversibly binds to the covalent intermediate DNA-enzyme, stabilizing the cleavable complex and reducing the religation rate. The stalled complex then collides with the progression of the replication fork, producing lethal double strand DNA breaks and eventually cell death. METHODOLOGY/PRINCIPAL FINDINGS: Long lasting molecular dynamics simulations of the DNA-topoisomerase I binary complex and of the DNA-topoisomerase-topotecan ternary complex have been performed and compared. The conformational space sampled by the binary complex is reduced by the presence of the drug, as observed by principal component and cluster analyses. This conformational restraint is mainly due to the reduced flexibility of residues 633-643 (the region connecting the linker to the core domain that causes an overall mobility loss in the ternary complex linker domain. During the simulation, DNA/drug stacking interactions are fully maintained, and hydrogen bonds are maintained with the enzyme. Topotecan keeps the catalytic residue Lys532 far from the DNA, making it unable to participate to the religation reaction. Arg364 is observed to interact with both the B and E rings of topotecan with two stable direct hydrogen bonds. An interesting constrain exerted by the protein on the geometrical arrangement of topotecan is also observed. CONCLUSIONS/SIGNIFICANCE: Atomistic-scale understanding of topotecan interactions with the DNA-enzyme complex is fundamental to the explaining of its poisonous effect and of the drug resistance observed in several single residue topoisomerase mutants. We observed significant alterations due to topotecan in

  4. Characterization of a novel mechanism accounting for the adverse cholinergic effects of the anticancer drug irinotecan

    Science.gov (United States)

    Blandizzi, Corrado; De Paolis, Barbara; Colucci, Rocchina; Lazzeri, Gloria; Baschiera, Fabio; Del Tacca, Mario

    2001-01-01

    This study investigates the mechanisms accounting for the adverse cholinergic effects of the antitumour drug irinotecan. The activity of irinotecan and its active metabolite, 7-ethyl-10-hydroxy-camptothecin (SN-38), was assayed in models suitable for pharmacological studies on cholinergic system. Irinotecan moderately inhibited human or electric eel acetylcholinesterase activity, SN-38 had no effect, whereas physostigmine blocked both the enzymes with high potency and efficacy. Irinotecan and SN-38 did not affect spontaneous or electrically-induced contractile activity of human colonic muscle. Acetylcholine and dimethylphenylpiperazinium (DMPP) caused phasic contractions or relaxations, respectively. Physostigmine enhanced the motor responses elicited by electrical stimulation. Although irinotecan and SN-38 did not modify the basal contractile activity of guinea-pig ileum longitudinal muscle strips, irinotecan 100 μM moderately enhanced cholinergic twitch contractions. Acetylcholine or DMPP caused phasic contractions, whereas physostigmine enhanced the twitch responses. Electrically-induced [3H]-acetylcholine release was reduced by irinotecan (100 μM) or physostigmine (0.1 μM). Intravenous irinotecan stimulated gastric acid secretion in rats, but no effects were obtained with SN-38, physostigmine or i.c.v. irinotecan. Hypersecretion induced by irinotecan was partly prevented by ondansetron, and unaffected by capsazepine. In the presence of atropine, vagotomy and systemic or vagal ablation of capsaicin-sensitive afferent fibres, irinotecan did not stimulate gastric secretion. The present results indicate that irinotecan and SN-38 do not act as specific acetylcholinesterase blockers or acetylcholine receptor agonists. It is rather suggested that irinotecan promotes a parasympathetic discharge to peripheral organs, mediated by capsaicin-sensitive vagal afferent fibres, and that serotonin 5-HT3 receptors are implicated in the genesis of vago-vagal reflex

  5. Anticancer effect of two diterpenoid compounds isolated from Annona glabra Linn

    Institute of Scientific and Technical Information of China (English)

    Yong-hong ZHANG; Hai-yan PENG; Guo-hao XIA; Ming-yan WANG; Ying HAN

    2004-01-01

    AIM: To study the inhibitory effect of two diterpenoid compounds isolated from Annona glabra Linn (Cunabic acid and ent-kauran-19-al-17-oic acid) on the proliferation of Human Liver Cancer (HLC) cell line SMMC-7721 and its mechanism. METHODS: Inhibition of cell proliferation was measured by MTT assay. The morphological changes of SMMC-7721 cells were observed under inverted phase-contrast microscope, fluorescent microscope,transmission electron microscope (TEM), and scanning electron microscope (SEM). Flow cytometer (FCM) was used to calculate the cell apoptotic rate, and immunohistochemical staining was used to observe the regulation of gene expression. RESULTS: The proliferation of SMMC-7721 cells was obviously inhibited after being treated with Cunabic acid at the concentration >5 μmol/L and ent-kauran-19-al-17-oic acid >10 μmol/L. The biggest inhibitory effect was 81.05 % when treated with Cunabic acid at the concentration of 25 μmol/L. The effect had a linear relationship with concentration. The result indicated that drug-treated cells exhibit typical morphological changes of apoptosis, including condensed chromatin and a reduction in volume. Sub-G0/G1 peak was found by FCM analysis and the cell cycle was arrested at G0/G1 stage. The apoptotic rates of the cells treated by Cunabic acid and ent-kauran-19-al-17-oic acid were 43.31% and 24.95 %, respectively. It was visualized by immunohistochemical staining that the d.rugs down-regulated the gene expression of bcl-2 gene and up-regulated that of bax gene. CONCLUSION: The two diterpenoid compounds isolated from Annona glabra Linn, Cunabic acid and entkauran-19-al-17-oic acid can obviously inhibit the proliferation of HLC cell line SMMC-7721. The mechanism is correlated with the induction of cell apoptosis by down-regulating the gene expression of bcl-2 gene and upregulating that of bax gene.

  6. The anticancer effect of saffron in two p53 isogenic colorectal cancer cell lines

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    Bajbouj Khuloud

    2012-05-01

    Full Text Available Abstract Background Saffron extract, a natural product, has been shown to induce apoptosis in several tumor cell lines. Nevertheless, the p53-dependency of saffron’s mechanism of action in colon cancer remains unexplored. Material and methods In order to examine saffron’s anti-proliferative and pro-apoptotic effects in colorectal cancer cells, we treated two p53 isogenic HCT116 cell lines (HCT wildtype and HCT p53−/− with different doses of the drug and analyzed cell proliferation and apoptosis in a time-dependent manner. MTT viability and crystal violet assays were performed in order to determine the effective dose of saffron on both cell lines. The cell cycle progress was examined by Flow cytometric analysis. Apoptosis was assessed using Annexin-PI-staining and Western Blotting for caspase 3 and PARP cleavage. Autophagy was determined by Western Blotting of the light chain 3 (LC3-II and Beclin 1 proteins. The protein content of phospho-H2AX (γH2AX, a sensor of DNA double strand breaks, was also analyzed by Western Blotting. Results Saffron extract induced a p53-dependent pattern of cell cycle distribution with a full G2/M stop in HCT116 p53 wildtype cells. However, it induced a remarkable delay in S/G2 phase transit with entry into mitosis in HCT116 p53 −/− cells. The apoptotic Pre-G1 cell fraction as well as Annexin V staining and caspase 3 cleavage showed a more pronounced apoptosis induction in HCT116 p53 wildtype cells. Obviously, the significantly higher DNA-damage, reflected by ɣH2AX protein levels in cells lacking p53, was coped by up-regulation of autophagy. The saffron-induced LC3-II protein level was a remarkable indication of the accumulation of autophagosomes, a response to the cellular stress condition of drug treatment. Conclusions This is the first study showing the effect of saffron in HCT116 colorectal cancer cells with different p53 status. Saffron induced DNA-damage and apoptosis in both cell lines. However

  7. The anticancer effect of saffron in two p53 isogenic colorectal cancer cell lines

    OpenAIRE

    Bajbouj Khuloud; Schulze-Luehrmann Jan; Diermeier Stefanie; Amin Amr; Schneider-Stock Regine

    2012-01-01

    Abstract Background Saffron extract, a natural product, has been shown to induce apoptosis in several tumor cell lines. Nevertheless, the p53-dependency of saffron’s mechanism of action in colon cancer remains unexplored. Material and methods In order to examine saffron’s anti-proliferative and pro-apoptotic effects in colorectal cancer cells, we treated two p53 isogenic HCT116 cell lines (HCT wildtype and HCT p53−/−) with different doses of the drug and analyzed cell proliferation and apopto...

  8. Studies on the mechanism by which indomethacin increases the anticancer effect of methotrexate.

    OpenAIRE

    Bennett, A.; Gaffen, J. D.; Melhuish, P. B.; Stamford, I. F.

    1987-01-01

    The effect of indomethacin on the response of the NC carcinoma to methotrexate has been examined in vivo and in vitro. Survival was prolonged in mice treated with indomethacin 1.25 mg kg-1 twice daily plus methotrexate 4 mg kg-1 daily, compared to mice given either drug alone or controls. Indomethacin 1 microgram ml-1 increased the killing of cultured NC cells by methotrexate. This was not due to displacement of methotrexate from binding sites on the serum proteins. Nor was it due (entirely) ...

  9. Study of combination treatment effect of the {sup 166}Ho and anticancer agents in-vitro

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, S. M.; Choi, S. J.; Park, K. B. [KAERI, Taejon (Korea, Republic of)

    2003-10-01

    For the development of new controlled drug delivery systems, the application of combination therapy using radioisotopes and tumor static agents has drawn great attention. This study was designed to estimate the treatment effect of the combination therapy with Holmium ({sup 166}Ho) and tumor static agents. Ho-166 was produced at the KAERI using HANARO reactor. The drugs applied were Sunpla, Methotrexate and Doxorubicin. Human glioblastoma (T98G), adenocarcinoma (MKN45), hepatocellular (Hep3B), lung carcinoma (Calu6), ovary adenocarcinoma (NIH:OVCAR- 3) and rat glioma (C6) were used. The cell cytotoxicity on the tumor cell lines determined by MTT assay. In the case where the chemotherapeutic agent was solely applied to the cell lines, the IC{sub 50} values wer e 2.4x10{sup -5}M of the Sunpla for MKN45 and 4.23x10{sup -6}M of the Doxorubicin for Calu6. The radioactivity of Ho-166 occurring 20% apoptosis was 10{mu}Ci. As for Sunpla and Doxorubicin, the value of IC20 was dependent on the cell lines used. The combination treatment of {sup 166}Ho and drug was to improve therapeutic success rate in T98G, MKN45, Hep3B, and Calu6. From this in vitro study it can be concluded that combining 166Ho radionuclide therapy and chemotherapy could enhance the effect of each in eliminating proliferating tumor cells.

  10. Anti-cancer effect of Cassia auriculata leaf extract in vitro through cell cycle arrest and induction of apoptosis in human breast and larynx cancer cell lines.

    Science.gov (United States)

    Prasanna, R; Harish, C C; Pichai, R; Sakthisekaran, D; Gunasekaran, P

    2009-02-01

    The in vitro anti-cancer effect of Cassia auriculata leaf extract (CALE) was evaluated in human breast adenocarcinoma MCF-7 and human larynx carcinoma Hep-2 cell lines. CALE preferentially inhibited the growth of both the cell lines in a dose-dependent manner with IC(50) values of 400 and 500 microg for MCF-7 and Hep-2 cells, respectively. The results showed the anti-cancer action is due to nuclear fragmentation and condensation, associated with the appearance of A(0) peak in cell cycle analysis that is indicative of apoptosis. In addition, CALE treated MCF-7 and Hep-2 cells had decreased expression of anti-apoptotic Bcl-2 protein and increased expression of pro-apoptotic Bax protein, eventually leading a decrease in the Bcl-2/Bax ratio. These results demonstrated that CALE inhibits the proliferation of MCF-7 and Hep-2 cells through induction of apoptosis, making CALE a candidate as new anti-cancer drug. PMID:18996213

  11. Effect of brefeldin A and castanospermine on resistant cell lines as supplements in anticancer therapy.

    Science.gov (United States)

    Wojtowicz, Karolina; Januchowski, Radosław; Sosińska, Patrycja; Nowicki, Michał; Zabel, Maciej

    2016-05-01

    In the present study, we analyzed the influence of brefeldin A (BFA) and castanospermine (CAS) on the activity, stability and localization of P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) in various resistant cell lines. The impact of BFA and CAS on cell viability was assessed using the MTT test. Western blotting (WB) was performed to assess the effect of the inhibitors on the expression of the investigated proteins. Immunofluorescence was employed to assess the effect of BFA and CAS on the cellular localization of the proteins. Flow cytometry was used to verify the functional role of inhibitors on drug uptake and efflux. The MTT test showed that BFA had a significant effect on cell viability in LoVo/Dx and W1PR cell lines. WB analysis demonstrated that BFA partially blocked Pgp N-glycosylation and induced BCRP degradation and CASP 3-dependent apoptosis in W1TR cells; however, the BFA activity was p53-independent. CAS had no effect on the stability of Pgp but increased the level of non-glycosylated BCRP. The expression of p53 protein decreased in all of the cells that were treated with CAS. Immunofluorescence revealed that BFA caused a more granular Pgp signal in W1PR and BCRP in A2780T1 cells. Furthermore, BFA caused morphological changes in LoVo/Dx and W1TR cell lines. CAS also induced a granular signal in all of the cell lines, except W1TR. The flow cytometry showed higher dye accumulation in sensitive cell lines. We observed an increase in the mean fluorescence intensity (MFI) of Rho123 in LoVo/Dx cells treated with BFA and CAS, but no differences were observed in W1PR. BFA had no effect on the MFI of W1TR, but CAS led to an increase in the level of intracellular H33342 in W1TR and A2780T1 cells. These results suggest that these compounds are likely to be useful as supplements in anticancer therapy. PMID:26985570

  12. The CYP51F1 Gene of Leptographium qinlingensis: Sequence Characteristic, Phylogeny and Transcript Levels

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    Lulu Dai

    2015-05-01

    Full Text Available Leptographium qinlingensis is a fungal associate of the Chinese white pine beetle (Dendroctonus armandi and a pathogen of the Chinese white pine (Pinus armandi that must overcome the terpenoid oleoresin defenses of host trees. L. qinlingensis responds to monoterpene flow with abundant mechanisms that include export and the use of these compounds as a carbon source. As one of the fungal cytochrome P450 proteins (CYPs, which play important roles in general metabolism, CYP51 (lanosterol 14-α demethylase can catalyze the biosynthesis of ergosterol and is a target for antifungal drug. We have identified an L. qinlingensis CYP51F1 gene, and the phylogenetic analysis shows the highest homology with the 14-α-demethylase sequence from Grosmannia clavigera (a fungal associate of Dendroctonus ponderosae. The transcription level of CYP51F1 following treatment with terpenes and pine phloem extracts was upregulated, while using monoterpenes as the only carbon source led to the downregulation of CYP5F1 expression. The homology modeling structure of CYP51F1 is similar to the structure of the lanosterol 14-α demethylase protein of Saccharomyces cerevisiae YJM789, which has an N-terminal membrane helix 1 (MH1 and transmembrane helix 1 (TMH1. The minimal inhibitory concentrations (MIC of terpenoid and azole fungicides (itraconazole (ITC and the docking of terpenoid molecules, lanosterol and ITC in the protein structure suggested that CYP51F1 may be inhibited by terpenoid molecules by competitive binding with azole fungicides.

  13. The CYP51F1 Gene of Leptographium qinlingensis: Sequence Characteristic, Phylogeny and Transcript Levels.

    Science.gov (United States)

    Dai, Lulu; Li, Zhumei; Yu, Jiamin; Ma, Mingyuan; Zhang, Ranran; Chen, Hui; Pham, Thanh

    2015-01-01

    Leptographium qinlingensis is a fungal associate of the Chinese white pine beetle (Dendroctonus armandi) and a pathogen of the Chinese white pine (Pinus armandi) that must overcome the terpenoid oleoresin defenses of host trees. L. qinlingensis responds to monoterpene flow with abundant mechanisms that include export and the use of these compounds as a carbon source. As one of the fungal cytochrome P450 proteins (CYPs), which play important roles in general metabolism, CYP51 (lanosterol 14-α demethylase) can catalyze the biosynthesis of ergosterol and is a target for antifungal drug. We have identified an L. qinlingensis CYP51F1 gene, and the phylogenetic analysis shows the highest homology with the 14-α-demethylase sequence from Grosmannia clavigera (a fungal associate of Dendroctonus ponderosae). The transcription level of CYP51F1 following treatment with terpenes and pine phloem extracts was upregulated, while using monoterpenes as the only carbon source led to the downregulation of CYP5F1 expression. The homology modeling structure of CYP51F1 is similar to the structure of the lanosterol 14-α demethylase protein of Saccharomyces cerevisiae YJM789, which has an N-terminal membrane helix 1 (MH1) and transmembrane helix 1 (TMH1). The minimal inhibitory concentrations (MIC) of terpenoid and azole fungicides (itraconazole (ITC)) and the docking of terpenoid molecules, lanosterol and ITC in the protein structure suggested that CYP51F1 may be inhibited by terpenoid molecules by competitive binding with azole fungicides. PMID:26016505

  14. Protamine nanoparticles for improving shRNA-mediated anti-cancer effects

    Science.gov (United States)

    Liu, Ming; Feng, Bo; Shi, Yijie; Su, Chang; Song, Huijuan; Cheng, Wei; Zhao, Liang

    2015-03-01

    Protamine nanoparticles were designed by encapsulating small hairpin RNA (shRNA)-expressing plasmid DNA targeting the Bcl-2 gene (shBcl-2) to silence apoptosis-related Bcl-2 protein for improving the transfection efficiency and cytotoxicity in cancer therapy. Our findings demonstrated that the obtained protamine nanoparticles possessed excellent characterizations of small particle size, homogenous distribution, positive charge, and high encapsulation efficiency of gene. shBcl-2 loaded in nanoparticles (NPs) was protected effectively from the degradation of DNase I and serum. More importantly, it significantly improved the efficiency of transfection of shRNA in vitro in A549 cells and increased its cytotoxicity and induced more cell apoptosis by silencing Bcl-2.

  15. Anti-cancer effect of thiacremonone through down regulation of peroxiredoxin 6.

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    Miran Jo

    Full Text Available Thiacremonone (2, 4-dihydroxy-2, 5-dimethyl-thiophene-3-one is an antioxidant substance as a novel sulfur compound generated from High-Temperature-High-Pressure-treated garlic. Peroxiredoxin 6 (PRDX6 is a member of peroxidases, and has glutathione peroxidase and calcium-independent phospholipase A2 (iPLA2 activities. Several studies have demonstrated that PRDX6 stimulates lung cancer cell growth via an increase of glutathione peroxidase activity. A docking model study and pull down assay showed that thiacremonone completely fits on the active site (cys-47 of glutathione peroxidase of PRDX6 and interacts with PRDX6. Thus, we investigated whether thiacremonone inhibits cell growth by blocking glutathione peroxidase of PRDX6 in the human lung cancer cells, A549 and NCI-H460. Thiacremonone (0-50 μg/ml inhibited lung cancer cell growth in a concentration dependent manner through induction of apoptotic cell death accompanied by induction of cleaved caspase-3, -8, -9, Bax, p21 and p53, but decrease of xIAP, cIAP and Bcl2 expression. Thiacremonone further inhibited glutathione peroxidase activity in lung cancer cells. However, the cell growth inhibitory effect of thiacremonone was not observed in the lung cancer cells transfected with mutant PRDX6 (C47S and in the presence of dithiothreitol and glutathione. In an allograft in vivo model, thiacremonone (30 mg/kg also inhibited tumor growth accompanied with the reduction of PRDX6 expression and glutathione peroxidase activity, but increased expression of cleaved caspase-3, -8, -9, Bax, p21 and p53. These data indicate that thiacremonone inhibits tumor growth via inhibition of glutathione peroxidase activity of PRDX6 through interaction. These data suggest that thiacremonone may have potentially beneficial effects in lung cancer.

  16. Experimental study on the anticancer effect of curcumin on mouse of S180 in vivo

    Institute of Scientific and Technical Information of China (English)

    ZHAO Dong-li; LI Ming-zhong; WANG Shu-wen; SHANG Ju-zhan

    2007-01-01

    Objective:To study curcumin's growth inhibitory effects and morphology changes on sarcoma graft's of S180 mouse,with further inquiry into the possible mechanisms.Methods:Thirty S180 mouse were randomly assigned into 3 groups:saline group (blank control group),Cytoxan group (positive control group)and curcumin group.The tumor inhibitory rates,the index of thymus and spleen,the growth of tumor and the change of pathology-morph,the index of apoptosis cells and morphology changes of apoptosis cells in the different groups were observed.Results:(1) Tumor's inhibitory rate in curcumin group and cytoxan group was 68.32% and 70.43%,respectively.Compared to blank control group,the 2 groups had significant elevated tumor inhibitory rate(P<0.01).(2) Thymus index of curcumin group did not have significant decrease compared to blank control group (P>0.05).(3)Under electroscope,curcumin group and positive control group had significant decrease in terms of growth of tumor,degree of infiltration of tumor,the number of nucleus fission,and blood vessels number compared to saline group (P<0.05).However,the degree of cell necrosis,the number of splenic segments and macrophage are increased significantly compared to negative group.(4) Accumulative score of apoptosis cell in curcumin group was significantly higher than other two groups(P<0.05).Conclusion:Internal organ study and cell morphology observation show curcumin can effectively inhibit the growth and cause the death of sarcoma graft of S180 mouse without interference with thymus.

  17. Anticancer Effect of Rutin Isolated from the Methanolic Extract of Triticum aestivum Straw in Mice

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    Savita Dixit

    2014-10-01

    Full Text Available Rutin is the bioactive flavanoid isolated from the straw part of Triticum aestivum and possess various pharmacological applications. The aim of this study is to evaluate the chemopreventive potential of rutin in an experimental skin carcinogenesis mice model system. Skin tumor was induced by topical application of 7,12-dimethyl benz(a anthracene (DMBA and promoted by croton oil in Swiss albino mice. To assess the chemopreventive potential of rutin, it was orally administered at a concentration of (200 mg/kg and 400 mg/kg body weight continued three times weekly for 16th weeks. The development of skin carcinogenesis was assessed by histopathological analysis. Reductions in tumor size and cumulative number of papillomas were seen due to rutin treatment. Average latent period was significantly increased as compared to carcinogen treated control. Rutin produced significant decrease in the activity of serum enzyme serum glutamate oxalate transaminase (SGOT, serum glutamate pyruvate transaminase (SGPT, alkaline phosphatase (ALP and bilirubin when compared with the control. They significantly increased the levels of enzyme involved in oxidative stress glutathione (GSH, superoxide dismutase (SOD and catalase. The elevated level of lipid peroxidase in the control group was significantly inhibited by rutin administration. The results from the present study suggest the chemopreventive effect of rutin in DMBA and croton oil induced skin carcinogenesis in swiss albino mice and one of the probable reasons would be its antioxidant potential.

  18. In Vitro and In Vivo Anticancer Effects of Sterol Fraction from Red Algae Porphyra dentata

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    Katarzyna Kazłowska

    2013-01-01

    Full Text Available Porphyra dentata, an edible red macroalgae, is used as a folk medicine in Asia. This study evaluated in vitro and in vivo the protective effect of a sterol fraction from P. dentata against breast cancer linked to tumor-induced myeloid derived-suppressor cells (MDSCs. A sterol fraction containing cholesterol, β-sitosterol, and campesterol was prepared by solvent fractionation of methanol extract of P. dentata  in silica gel column chromatography. This sterol fraction in vitro significantly inhibited cell growth and induced apoptosis in 4T1 cancer cells. Intraperitoneal injection of this sterol fraction at 10 and 25 mg/kg body weight into 4T1 cell-implanted tumor BALB/c mice significantly inhibited the growth of tumor nodules and increased the survival rate of mice. This sterol fraction significantly decreased the reactive oxygen species (ROS and arginase activity of MDSCs in tumor-bearing mice. Therefore, the sterol fraction from P. dentata showed potential for protecting an organism from 4T1 cell-based tumor genesis.

  19. Antiangiogenesis as the novel mechanism for justicidin A in the anticancer effect on human bladder cancer.

    Science.gov (United States)

    Wang, Yi-Wen; Chuang, Jing-Jing; Chang, Tsuey-Yu; Won, Shen-Jeu; Tsai, Hung-Wen; Lee, Chung-Ta; Cheng, Hong-Lin; Tzai, Tzong-Shin; Liu, Hsiao-Sheng; Chow, Nan-Haw

    2015-04-01

    Justicidin A (JA) is one of the methanol extracts of Justicia procumbens and was reported to induce apoptosis and inhibit the proliferation of human colon cancer cells. Using bladder cancer as a paradigm, this study was designed to identify the novel molecular basis underlying the antiangiogenic activities of JA and its potential in cancer therapy. Human bladder cancer cell lines (TSGH8301 and RT4) and immortalized uroepithelial cell lines (E6 and E7) were chosen to investigate the efficacy of JA in cell proliferation, apoptosis, and angiogenesis in vitro. The biological effects of JA treatment in vivo were examined using a xenograft tumor model in SCID mice. JA showed a dose-dependent and time-dependent inhibition of cell proliferation on TSGH8301 cancer cells, with IC50 values determined to be 0.44 μmol/l. Of interest, TSGH8301 cancer cells were more sensitive to JA than E7 immortalized uroepithelial cells, especially at lower concentrations. We further showed that JA inhibited the autocrine production of angiogenic factors and matrix-degrading enzymes in vitro and microvessel density in SCID mice in vivo (P< 0.01). Both differential cytotoxicity and angiogenesis inhibition of JA were confirmed by SCID mice experiments. Together, JA showed antiangiogenesis in vitro and in vivo through pleiotropic positive and negative regulators of angiogenesis molecules. The current investigation supports the potential of JA as an alternative chemoprevention agent for human bladder cancer. PMID:25569706

  20. Regulation of leptin on insulin secretion and sulfonulurea receptor 1 transcription level in isolated rats pancreatic islets

    Institute of Scientific and Technical Information of China (English)

    袁莉; 安汉祥; 邓秀玲; 李卓娅

    2003-01-01

    Objective To investigate the regulation of leptin on insulin secretion and expression of ATP-sensitive potassium channel subunit sulfonulurea receptor 1 (SUR1) mRNA, and to determine whether the effects of leptin are mediated through known intracellular signaling transduction. Methods Pancreatic islets were isolated by the collagenase method from male SD rats. The purified islets were incubated with different concentrations of leptin for 2 h in the presence of different concentrations of glucose. Insulin release was measured using radioimmunoassay. Expression of SUR1 mRNA was detected by RT-PCR. Results In the presence of leptin 2 nmol/L, insulin release was significantly inhibited at either 11.1 or 16.7 mmol/L glucose concentration (bothP<0.05), but insulin release was not altered at glucose of 5.6 mmol/L physiological concentration. The dose-response experiment showed that the maximal effect of leptin on insulin secretion achieved at 2 nmol/L. Exposure of islets to 2 nmol/L leptin induced a significant increase of SUR1 transcription evels by 71% (P<0.01) at 11.1 mmol/L glucose and by 56% (P<0.05) at 16.7 mmol/L glucose concentration. Selective phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor wortmannin significantly prevented the leptin effect on insulin secretion and SUR1 mRNA expression. Conclusions Regulatory effects of leptin on insulin secretion could be biphasic at different concentrations of glucose and leptin. The stimulatory regulation of SUR1 transcription levels may be mediated through activation of PI 3-kinase pathway, which may be a possible mechanism of leptin in regulating insulin secretion.

  1. Quercetin induces cell cycle arrest and apoptosis in CD133+ cancer stem cells of human colorectal HT29 cancer cell line and enhances anticancer effects of doxorubicin

    Science.gov (United States)

    Atashpour, Shekoufeh; Fouladdel, Shamileh; Movahhed, Tahereh Komeili; Barzegar, Elmira; Ghahremani, Mohammad Hossein; Ostad, Seyed Nasser; Azizi, Ebrahim

    2015-01-01

    Objective(s): The colorectal cancer stem cells (CSCs) with the CD133+ phenotype are a rare fraction of cancer cells with the ability of self-renewal, unlimited proliferation and resistance to treatment. Quercetin has anticancer effects with the advantage of exhibiting low side effects. Therefore, we evaluated the anticancer effects of quercetin and doxorubicin (Dox) in HT29 cancer cells and its isolated CD133+ CSCs. Materials and Methods: The CSCs from HT29 cells were isolated using CD133 antibody conjugated to magnetic beads by MACS. Anticancer effects of quercetin and Dox alone and in combination on HT29 cells and CSCs were evaluated using MTT cytotoxicity assay and flow cytometry analysis of cell cycle distribution and apoptosis induction. Results: The CD133+ CSCs comprised about 10% of HT29 cells. Quercetin and Dox alone and in combination inhibited cell proliferation and induced apoptosis in HT29 cells and to a lesser extent in CSCs. Quercetin enhanced cytotoxicity and apoptosis induction of Dox at low concentration in both cell populations. Quercetin and Dox and their combination induced G2/M arrest in the HT29 cells and to a lesser extent in CSCs. Conclusion: The CSCs were a minor population with a significantly high level of drug resistance within the HT29 cancer cells. Quercetin alone exhibited significant cytotoxic effects on HT29 cells and also increased cytoxicity of Dox in combination therapy. Altogether, our data showed that adding quercetin to Dox chemotherapy is an effective strategy for treatment of both CSCs and bulk tumor cells. PMID:26351552

  2. Application of a Nonlinear Model to Transcript Levels of Upregulated Stress Response Gene ibpA in Stationary-Phase Salmonella enterica Subjected to Sublethal Heat Stress.

    Science.gov (United States)

    Carroll, Laura M; Bergholz, Teresa M; Hildebrandt, Ian M; Marks, Bradley P

    2016-07-01

    Sublethal heating, which can occur during slow cooking of meat products, is known to induce increased thermal resistance in Salmonella. However, very few studies have addressed the kinetics of this response. Although several recent studies have reported improved thermal inactivation models that include the effect of prior sublethal history on subsequent thermal resistance, none of these models were based on cellular-level responses to sublethal thermal stress. The goal of this study was to determine whether a nonlinear model could accurately portray the response of Salmonella to heat stress induced by prolonged exposure to sublethal temperatures. To accomplish this, stationary-phase Salmonella Montevideo cultures were subjected to various heating profiles (held at either 40 or 45°C for 0, 5, 10, 15, 30, 60, 90, 180, or 240 min) using a PCR thermal cycler. Differential plating on selective and nonselective media was used to confirm the presence of cellular injury. Reverse transcription quantitative PCR was used to screen the transcript levels of six heat stress-related genes to find candidate genes for nonlinear modeling. Injury was detected in populations of Salmonella held at 45°C for 30, 60, and 90 min and at 40°C for 0, 5, and 90 min (P 0.05). The transcript levels of ibpA, which codes for a small heat shock protein associated with the ClpB and DnaK-DnaJ-GrpE chaperone systems, showed the greatest increase relative to the transcript levels at 0 min, which was significant at 5, 10, 15, 30, 60, 90, and 180 min at 45°C and at 5, 10, 15, 30, 60, and 90 min at 40°C (P < 0.05). Using ibpA transcript levels as an indicator of adaptation to thermal stress, a nonlinear model for sublethal injury is proposed. The use of variables indicating the physiological state of the pathogen during stress has the potential to increase the accuracy of thermal inactivation models that must account for prolonged exposure to sublethal temperatures. PMID:27357027

  3. Resveratrol‑4‑O‑D‑(2'‑galloyl)‑glucopyranoside exerts an anticancer effect on leukemia cells via inducing apoptosis.

    Science.gov (United States)

    Chen, Pu; Wang, Beili; Pan, Baishen; Guo, Wei

    2016-03-01

    The aim of the present study was to investigate the anticancer effects of resveratrol‑4‑O‑D-(2'‑galloyl)-glucopyranoside (REG) on leukemia and the mechanism underlying its effects. Three leukemia cell lines (HL‑60, Jurkat and U937) were used in this study. A Cell Counting kit‑8 assay was performed to evaluate the anti‑proliferative activity of REG on leukemia cell lines, and flow cytometric analysis was used to detect REG‑induced apoptosis. In addition, western blot analysis was conducted to detect the levels of apoptosis‑related proteins including, cytochrome c, cleaved (c)‑caspases‑3 and ‑9, B‑cell lymphoma 2 (Bcl‑2) and Bcl‑2‑associated protein x (Bax). Finally, a HL‑60 cell xenograft model in nude mice was used to evaluate the antitumor effect of REG on leukemia in vivo. The present results indicated that REG can significantly inhibit the proliferation of HL‑60, Jurkat and U937 cell lines in a concentration‑ and time‑dependent manner. The half maximal inhibitory concentration values were 38.4, 49.1 and 48.2 µg/ml for HL‑60, Jurkat and U937 cells, respectively. Furthermore, flow cytometric analysis demonstrated that REG can induce the apoptosis of HL‑60 cells, as well as increase the levels of cytochrome c, c‑caspases‑3 and ‑9, and Bax, as well as downregulate the expression of Bcl‑2. In vivo, REG was found to possess a marked anticancer effect on leukemia. In combination, the present results indicated that REG exerts significant anticancer effects on leukemia in vivo and in vitro through the induction of apoptosis. PMID:26781500

  4. Structural and Dynamical Effects Induced by the Anticancer Drug Topotecan on the Human Topoisomerase I – DNA Complex

    OpenAIRE

    Mancini, Giordano; D'Annessa, Ilda; Coletta, Andrea; Sanna, Nico; Chillemi, Giovanni; Desideri, Alessandro

    2010-01-01

    Background Human topoisomerase I catalyzes the relaxation of DNA supercoils in fundamental cell processes like transcription, replication and chromosomal segregation. It is the only target of the camptothecin family of anticancer drugs. Among these, topotecan has been used to treat lung and ovarian carcinoma for several years. Camptothecins reversibly binds to the covalent intermediate DNA-enzyme, stabilizing the cleavable complex and reducing the religation rate. The stalled complex then col...

  5. Anticancer effect of metformin on estrogen receptor-positive and tamoxifen-resistant breast cancer cell lines.

    Science.gov (United States)

    Kim, Jinkyoung; Lee, Jiyun; Jang, Soon Young; Kim, Chungyeul; Choi, Yoojin; Kim, Aeree

    2016-05-01

    Acquisition of tamoxifen resistance (TR) during anti-estrogenic therapy using tamoxifen is a major obstacle in the treatment of estrogen receptor (ER)-positive breast cancer. As a biguanide derivative, metformin is commonly used to treat type II diabetes. It has recently emerged as a potential anticancer agent. The objective of the present study was to investigate the anticancer activity of metformin in relation to ERα expression and its signaling pathway in ERα-positive MCF-7 and MDA-MB-361 breast cancer cells as well as TR MCF-7 breast cancer cells. Metformin inhibited both protein and mRNA levels of ERα in the presence or absence of estrogen (E2) in the MCF-7, TR MCF-7 and MDA-MB-361 cells. Metformin repressed E2-inducible estrogen response element (ERE) luciferase activity, protein levels and mRNA levels of E2/ERα-regulated genes [including c-Myc, cyclin D1, progesterone receptor (PR) and pS2] to a greater degree than tamoxifen, resulting in inhibition of cell proliferation of MCF-7, TR MCF-7 and MDA-MB-361 cells. Collectively, our results suggest that one of the anticancer mechanisms of metformin could be attributable to the repression of expression and transcriptional activity of ERα. Metformin may be a good therapeutic agent for treating ERα-positive breast cancer by inhibiting the expression and function of ERα. In addition, metformin may be useful to treat tamoxifen-resistant breast cancer. PMID:26986571

  6. Effect of Amino Acids on the Generation of Ginsenoside Rg3 Epimers by Heat Processing and the Anticancer Activities of Epimers in A2780 Human Ovarian Cancer Cells.

    Science.gov (United States)

    Park, Jun Yeon; Choi, Pilju; Lee, Dahae; Kim, Taejung; Jung, Eun Bee; Hwang, Buyng-Su; Kang, Ki Sung; Ham, Jungyeob

    2016-01-01

    Ginsenosides are the active components of Panax ginseng. Many research studies indicate that these deglycosylated, less-polar ginsenosides have better bioactivity than the major ginsenosides. In the present study, we sought to verify the enhanced anticancer effect of P. ginseng extract after undergoing the Maillard reaction as well as elucidate the underlying mechanism of action. The effects of 9 amino acids were tested; among them, the content of 20(S)-Rg3 in the ginseng extract increased to more than 30, 20, and 20% when processed with valine, arginine, and alanine, respectively, compared with that after normal heat processing. The ginseng extract that was heat-processed with arginine exhibited the most potent inhibitory effect on A2780 ovarian cancer cell proliferation. Therefore, the generation of 20(S)-Rg3 was suggested to be involved in this effect. Moreover, the inhibitory effect of 20(S)-Rg3 on A2780 cell proliferation was significantly stronger than that of 20(R)-Rg3. Protein expression levels of cleaved caspase-3, caspase-8, caspase-9, and PARP in the A2780 ovarian cancer cells markedly increased, whereas the expression of BID decreased after 20(S)-Rg3 treatment. Therefore, we confirmed that the anticancer effects of the products of ginseng that was heat-processed with arginine are mediated mainly via the generation of the less-polar ginsenoside 20(S)-Rg3. PMID:27051448

  7. Effect of Amino Acids on the Generation of Ginsenoside Rg3 Epimers by Heat Processing and the Anticancer Activities of Epimers in A2780 Human Ovarian Cancer Cells

    Directory of Open Access Journals (Sweden)

    Jun Yeon Park

    2016-01-01

    Full Text Available Ginsenosides are the active components of Panax ginseng. Many research studies indicate that these deglycosylated, less-polar ginsenosides have better bioactivity than the major ginsenosides. In the present study, we sought to verify the enhanced anticancer effect of P. ginseng extract after undergoing the Maillard reaction as well as elucidate the underlying mechanism of action. The effects of 9 amino acids were tested; among them, the content of 20(S-Rg3 in the ginseng extract increased to more than 30, 20, and 20% when processed with valine, arginine, and alanine, respectively, compared with that after normal heat processing. The ginseng extract that was heat-processed with arginine exhibited the most potent inhibitory effect on A2780 ovarian cancer cell proliferation. Therefore, the generation of 20(S-Rg3 was suggested to be involved in this effect. Moreover, the inhibitory effect of 20(S-Rg3 on A2780 cell proliferation was significantly stronger than that of 20(R-Rg3. Protein expression levels of cleaved caspase-3, caspase-8, caspase-9, and PARP in the A2780 ovarian cancer cells markedly increased, whereas the expression of BID decreased after 20(S-Rg3 treatment. Therefore, we confirmed that the anticancer effects of the products of ginseng that was heat-processed with arginine are mediated mainly via the generation of the less-polar ginsenoside 20(S-Rg3.

  8. Bacteriocins as potential anticancer agents

    OpenAIRE

    Sukhraj eKaur; Sumanpreet eKaur

    2015-01-01

    Cancer remains one of the leading causes of deaths worldwide, despite advances in its treatment and detection. The conventional chemotherapeutic agents used for the treatment of cancer have nonspecific toxicity towards normal body cells that cause various side effects. Secondly, cancer cells are known to develop chemotherapy resistance in due course of treatment. Thus, the demand for novel anti-cancer agents is increasing day by day. Some of the experimental studies have reported the therapeu...

  9. Bacteriocins as Potential Anticancer Agents

    OpenAIRE

    Kaur, Sumanpreet; Kaur, Sukhraj

    2015-01-01

    Cancer remains one of the leading causes of deaths worldwide, despite advances in its treatment and detection. The conventional chemotherapeutic agents used for the treatment of cancer have non-specific toxicity toward normal body cells that cause various side effects. Secondly, cancer cells are known to develop chemotherapy resistance in due course of treatment. Thus, the demand for novel anti-cancer agents is increasing day by day. Some of the experimental studies have reported the therapeu...

  10. Warburg effect increases steady-state ROS condition in cancer cells through decreasing their antioxidant capacities (anticancer effects of 3-bromopyruvate through antagonizing Warburg effect).

    Science.gov (United States)

    El Sayed, Salah Mohamed; Mahmoud, Ahmed Alamir; El Sawy, Samer Ahmed; Abdelaal, Esam Abdelrahim; Fouad, Amira Murad; Yousif, Reda Salah; Hashim, Marwa Shaban; Hemdan, Shima Badawy; Kadry, Zainab Mahmoud; Abdelmoaty, Mohamed Ahmed; Gabr, Adel Gomaa; Omran, Faten M; Nabo, Manal Mohamed Helmy; Ahmed, Nagwa Sayed

    2013-11-01

    substrate G6P that is a direct product of HK II. 3-bromopyruvate (3BP, inhibitor of HK II) may prove as a promising anticancer and antimetastatic agent based on antagonizing the Warburg effect and disturbing the malignant behavior in cancer cells. PMID:24071366

  11. Enhanced Anti-Cancer Effect of Snake Venom Activated NK Cells on Lung Cancer Cells by Inactivation of NF-κB

    OpenAIRE

    Kollipara, Pushpa Saranya; Won, Do Hee; Hwang, Chul Ju; Jung, Yu Yeon; Yoon, Heui Seoung; Park, Mi Hee; Song, Min Jong; Song, Ho Sueb; Hong, Jin Tae

    2014-01-01

    In the present study, we investigated anti-cancer effect of snake venom activated NK cells (NK-92MI) in lung cancer cell lines. We used snake venom (4 μg/ml) treated NK-92MI cells to co-culture with lung cancer cells. There was a further decrease in cancer cell growth up to 65% and 70% in A549 and NCI-H460 cell lines respectively, whereas 30–40% was decreased in cancer cell growth by snake venom or NK-92MI alone treatment. We further found that the expression of various apoptotic proteins suc...

  12. Anticancer Molecular Mechanisms of Resveratrol

    Science.gov (United States)

    Varoni, Elena M.; Lo Faro, Alfredo Fabrizio; Sharifi-Rad, Javad; Iriti, Marcello

    2016-01-01

    Resveratrol is a pleiotropic phytochemical belonging to the stilbene family. Though it is only significantly present in grape products, a huge amount of preclinical studies investigated its anticancer properties in a plethora of cellular and animal models. Molecular mechanisms of resveratrol involved signaling pathways related to extracellular growth factors and receptor tyrosine kinases; formation of multiprotein complexes and cell metabolism; cell proliferation and genome instability; cytoplasmic tyrosine kinase signaling (cytokine, integrin, and developmental pathways); signal transduction by the transforming growth factor-β super-family; apoptosis and inflammation; and immune surveillance and hormone signaling. Resveratrol also showed a promising role to counteract multidrug resistance: in adjuvant therapy, associated with 5-fluoruracyl and cisplatin, resveratrol had additive and/or synergistic effects increasing the chemosensitization of cancer cells. Resveratrol, by acting on diverse mechanisms simultaneously, has been emphasized as a promising, multi-target, anticancer agent, relevant in both cancer prevention and treatment.

  13. The flavonoid p-hydroxycinnamic acid exhibits anticancer effects in human pancreatic cancer MIA PaCa-2 cells in vitro: Comparison with gemcitabine.

    Science.gov (United States)

    Yamaguchi, Masayoshi; Murata, Tomiyasu; El-Rayes, Bassel F; Shoji, Mamoru

    2015-12-01

    Pancreatic cancer is a highly aggressive malignancy with a notoriously dismal prognosis. A major contributor to this poor clinical outcome is pancreatic cancer's prominent chemoresistance. The present study was undertaken to determine whether the flavonoid p‑hydroxycinnamic acid (HCA), which is a botanical factor, possesses anticancer effects on cloned human pancreatic cancer MIA PaCa‑2 cells that possess resistance to radiation therapy in vitro. Proliferation of MIA PaCa‑2 cells was suppressed after culture with HCA (10‑1,000 nM). Such an effect was also noted in human pancreatic cancer Pt45P1 cells. In the MIA PaCa‑2 cells, HCA induced G1 and G2/M phase cell cycle arrest in the cells. The suppressive effects of HCA on proliferation were suggested to be mediated through the inhibition of various signaling pathways related to nuclear factor‑κB (NF‑κB), extracellular signal‑regulated kinase (ERK), protein kinase C, phosphatidylinositol 3‑kinase (PI3K) or nuclear transcription activity. Moreover, HCA was found to stimulate cell death in the MIA PaCa‑2 and Pt45P1 cells in vitro. The anticancer effects of HCA on MIA PaCa‑2 cells were exhibited at a lower concentration than gemcitabine, a potent cancer drug. The flavonoid HCA may be a useful tool in the therapy of human pancreatic cancer in vivo. PMID:26397991

  14. Anticancer and Cancer Prevention Effects of Piperine-Free Piper nigrum Extract on N-nitrosomethylurea-Induced Mammary Tumorigenesis in Rats.

    Science.gov (United States)

    Sriwiriyajan, Somchai; Tedasen, Aman; Lailerd, Narissara; Boonyaphiphat, Pleumjit; Nitiruangjarat, Anupong; Deng, Yan; Graidist, Potchanapond

    2016-01-01

    Piper nigrum (P. nigrum) is commonly used in traditional medicine. This current study aimed to investigate the anticancer and cancer preventive activity of a piperine-free P. nigrum extract (PFPE) against breast cancer cells and N-nitrosomethylurea (NMU)-induced mammary tumorigenesis in rats. The cytotoxic effects and the mechanism of action were investigated in breast cancer cells using the MTT assay and Western blot analysis, respectively. An acute toxicity study was conducted according to the Organization for Economic Co-operation and Development guideline. Female Sprague-Dawley rats with NMU-induced mammary tumors were used in preventive and anticancer studies. The results showed that PFPE inhibited the growth of luminal-like breast cancer cells more so than the basal-like ones by induction of apoptosis. In addition, PFPE exhibited greater selectivity against breast cancer cells than colorectal cancer, lung cancer, and neuroblastoma cells. In an acute toxicity study, a single oral administration of PFPE at a dose of 5,000 mg/kg body weight resulted in no mortality and morbidity during a 14-day observation period. For the cancer preventive study, the incidence of tumor-bearing rats was 10% to 20% in rats treated with PFPE. For the anticancer activity study, the growth rate of tumors in the presence of PFPE-treated groups was much slower when compared with the control and vehicle groups. The extract itself caused no changes to the biochemical and hematologic parameters when compared with the control and vehicle groups. In conclusion, PFPE had a low toxicity and a potent antitumor effect on mammary tumorigenesis in rats. PMID:26511488

  15. Evaluation of the toxic effects of four anti-cancer drugs in plant bioassays and its potency for screening in the context of waste water reuse for irrigation.

    Science.gov (United States)

    Lutterbeck, Carlos Alexandre; Kern, Deivid Ismael; Machado, Ênio Leandro; Kümmerer, Klaus

    2015-09-01

    Anti-cancer drugs are compounds that are of high environmental relevance because of their lack of specific mode of action. They can be extremely harmful to living organisms even at low concentrations. The present study evaluated the toxic effects of four frequently used anti-cancer drugs against plant seedlings, namely Cyclophosphamide (CP), Methotrexate (MTX), 5-Fluorouracil (5-FU) and Imatinib (IM). The phytotoxicity experiments were performed with Lactuca sativa seedlings whereas cytotoxicity, genotoxicity and mutagenicity investigations were performed with the well-established Allium cepa assays. MTX was the most phytotoxic compound, followed by 5-FU, CP and IM. Significant differences in the Mitotic Indexes (MI) were observed in three of the studied compounds (MTX, 5-FU and CP), indicating potential cytotoxic activity of these substances. Chromosome aberrations were registered in cells that were exposed to 5-FU, CP and IM. All the four compounds caused the formation of micronucleated cells indicating mutagenic potential. Besides, the assays performed with MTX samples presented a high number of cell apoptosis (cell death). Although it is unlikely that the pharmaceuticals concentrations measured in the environment could cause lethal effects in plants, the obtained results indicate that these compounds may affect the growth and normal development of these plants. So, both tests can constitute important tools for a fast screening of environmental contamination e.g. in the context of the reuse of treated wastewater and biosolids of agricultural purpose. PMID:26002047

  16. Proapoptotic and Antiproliferative Effects of Thymus caramanicus on Human Breast Cancer Cell Line (MCF-7 and Its Interaction with Anticancer Drug Vincristine

    Directory of Open Access Journals (Sweden)

    Saeed Esmaeili-Mahani

    2014-01-01

    Full Text Available Thymus caramanicus Jalas is one of the species of thymus that grows in the wild in different regions of Iran. Traditionally, leaves of this plant are used in the treatment of diabetes, arthritis, and cancerous situation. Therefore, the present study was designed to investigate the selective cytotoxic and antiproliferative properties of Thymus caramanicus extract (TCE. MCF-7 human breast cancer cells were used in this study. Cytotoxicity of the extract was determined using MTT and neutral red assays. Biochemical markers of apoptosis (caspase 3, Bax, and Bcl-2 and cell proliferation (cyclin D1 were evaluated by immunoblotting. Vincristine was used as anticancer control drug in extract combination therapy. The data showed that incubation of cells with TCE (200 and 250 μg/mL significantly increased cell damage, activated caspase 3 and Bax/Bcl2 ratio. In addition, cyclin D1 was significantly decreased in TCE-treated cells. Furthermore, concomitant treatment of cells with extract and anticancer drug produced a significant cytotoxic effect as compared to extract or drugs alone. In conclusion, thymus extract has a potential proapoptotic/antiproliferative property against human breast cancer cells and its combination with chemotherapeutic agent vincristine may induce cell death effectively and be a potent modality to treat this type of cancer.

  17. A network biology approach evaluating the anticancer effects of bortezomib identifies SPARC as a therapeutic target in adult T-cell leukemia cells

    Directory of Open Access Journals (Sweden)

    Yu Zhang

    2008-10-01

    Full Text Available Junko H Ohyashiki1, Ryoko Hamamura2, Chiaki Kobayashi2, Yu Zhang2, Kazuma Ohyashiki21Intractable Immune System Disease Research Center, Tokyo Medical University, Tokyo, Japan; 2First Department of Internal Medicine, Tokyo Medical University, Tokyo, JapanAbstract: There is a need to identify the regulatory gene interaction of anticancer drugs on target cancer cells. Whole genome expression profiling offers promise in this regard, but can be complicated by the challenge of identifying the genes affected by hundreds to thousands of genes that induce changes in expression. A proteasome inhibitor, bortezomib, could be a potential therapeutic agent in treating adult T-cell leukemia (ATL patients, however, the underlying mechanism by which bortezomib induces cell death in ATL cells via gene regulatory network has not been fully elucidated. Here we show that a Bayesian statistical framework by VoyaGene® identified a secreted protein acidic and rich in cysteine (SPARC gene, a tumor-invasiveness related gene, as a possible modulator of bortezomib-induced cell death in ATL cells. Functional analysis using RNAi experiments revealed that inhibition of the expression SPARC by siRNA enhanced the apoptotic effect of bortezomib on ATL cells in accordance with an increase of cleaved caspase 3. Targeting SPARC may help to treat ATL patients in combination with bortezomib. This work shows that a network biology approach can be used advantageously to identify the genetic interaction related to anticancer effects.Keywords: network biology, adult T cell leukemia, bortezomib, SPARC

  18. Specific Design of Titanium(IV) Phenolato Chelates Yields Stable and Accessible, Effective and Selective Anticancer Agents.

    Science.gov (United States)

    Meker, Sigalit; Braitbard, Ori; Hall, Matthew D; Hochman, Jacob; Tshuva, Edit Y

    2016-07-11

    Octahedral titanium(IV) complexes of phenolato hexadentate ligands were developed and showed very high stability for days in water solutions. In vitro cytotoxicity studies showed that, whereas tetrakis(phenolato) systems are generally of low activity presumably due to inaccessibility, smaller bis(phenolato)bis(alkoxo) complexes feature high anticancer activity and accessibility even without formulations, also toward a cisplatin-resistant cell line. An all-aliphatic control complex was unstable and inactive. A leading phenolato complex also revealed: 1) high durability in fully aqueous solutions; accordingly, negligible loss of activity after preincubation for three days in medium or in serum; 2) maximal cellular accumulation and induction of apoptosis following 24-48 h of administration; 3) reduced impact on noncancerous fibroblast cells; 4) in vivo efficacy toward lymphoma cells in murine model; 5) high activity in NCI-60 panel, with average GI50 of 4.6±2 μm. This newly developed family of Ti(IV) complexes is thus of great potential for anticancer therapy. PMID:27320784

  19. Changes in Dietary Fat Content Rapidly Alters the Mouse Plasma Coagulation Profile without Affecting Relative Transcript Levels of Coagulation Factors

    Science.gov (United States)

    van Diepen, Janna A.; Verhoef, Daniël; Voshol, Peter J.; Reitsma, Pieter H.; van Vlijmen, Bart J. M.

    2015-01-01

    Background Obesity is associated with a hypercoagulable state and increased risk for thrombotic cardiovascular events. Objective Establish the onset and reversibility of the hypercoagulable state during the development and regression of nutritionally-induced obesity in mice, and its relation to transcriptional changes and clearance rates of coagulation factors as well as its relation to changes in metabolic and inflammatory parameters. Methods Male C57BL/6J mice were fed a low fat (10% kcal as fat; LFD) or high fat diet (45% kcal as fat; HFD) for 2, 4, 8 or 16 weeks. To study the effects of weight loss, mice were fed the HFD for 16 weeks and switched to the LFD for 1, 2 or 4 weeks. For each time point analyses of plasma and hepatic mRNA levels of coagulation factors were performed after overnight fasting, as well as measurements of circulating metabolic and inflammatory parameters. Furthermore, in vivo clearance rates of human factor (F) VII, FVIII and FIX proteins were determined after 2 weeks of HFD-feeding. Results HFD feeding gradually increased the body and liver weight, which was accompanied by a significant increase in plasma glucose levels from 8 weeks onwards, while insulin levels were affected after 16 weeks. Besides a transient rise in cytokine levels at 2 weeks after starting the HFD, no significant effect on inflammation markers was present. Increased plasma levels of fibrinogen, FII, FVII, FVIII, FIX, FXI and FXII were observed in mice on a HFD for 2 weeks, which in general persisted throughout the 16 weeks of HFD-feeding. Interestingly, with the exception of FXI the effects on plasma coagulation levels were not paralleled by changes in relative transcript levels in the liver, nor by decreased clearance rates. Switching from HFD to LFD reversed the HFD-induced procoagulant shift in plasma, again not coinciding with transcriptional modulation. Conclusions Changes in dietary fat content rapidly alter the mouse plasma coagulation profile, thereby

  20. Differential analyses for RNA-seq: transcript-level estimates improve gene-level inferences [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Charlotte Soneson

    2016-02-01

    Full Text Available High-throughput sequencing of cDNA (RNA-seq is used extensively to characterize the transcriptome of cells. Many transcriptomic studies aim at comparing either abundance levels or the transcriptome composition between given conditions, and as a first step, the sequencing reads must be used as the basis for abundance quantification of transcriptomic features of interest, such as genes or transcripts. Various quantification approaches have been proposed, ranging from simple counting of reads that overlap given genomic regions to more complex estimation of underlying transcript abundances. In this paper, we show that gene-level abundance estimates and statistical inference offer advantages over transcript-level analyses, in terms of performance and interpretability. We also illustrate that the presence of differential isoform usage can lead to inflated false discovery rates in differential gene expression analyses on simple count matrices but that this can be addressed by incorporating offsets derived from transcript-level abundance estimates. We also show that the problem is relatively minor in several real data sets. Finally, we provide an R package (tximport to help users integrate transcript-level abundance estimates from common quantification pipelines into count-based statistical inference engines.

  1. Dihydroartemisinin potentiates the anticancer effect of cisplatin via mTOR inhibition in cisplatin-resistant ovarian cancer cells: involvement of apoptosis and autophagy

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Xue [Department of Gynecology and Obstetrics, The First Affiliated Hospital of Harbin Medical University, Harbin 150001 (China); Li, Ling [Department of Brain Cognition Computing Lab, University of Kent, Kent CT2 7NZ (United Kingdom); Jiang, Hong; Jiang, Keping; Jin, Ye [Department of Gynecology and Obstetrics, The First Affiliated Hospital of Harbin Medical University, Harbin 150001 (China); Zheng, Jianhua, E-mail: zhengjianhua1115@126.com [Department of Gynecology and Obstetrics, The First Affiliated Hospital of Harbin Medical University, Harbin 150001 (China)

    2014-02-14

    Highlights: • Phosphorylation of mTOR is abnormal activation in SKOV3/DDP ovarian cancer cells. • Downregulation of mTOR by DHA helps to sensitize the SKOV3/DDP cells to chemotherapy. • DHA has the potential of induce autophagy in cancer cells. - Abstract: Dihydroartemisinin (DHA) exhibits anticancer activity in tumor cells but its mechanism of action is unclear. Cisplatin (DDP) is currently the best known chemotherapeutic available for ovarian cancer. However, tumors return de novo with acquired resistance over time. Mammalian target of rapamycin (mTOR) is an important kinase that regulates cell apoptosis and autophagy, and its dysregulation has been observed in chemoresistant human cancers. Here, we show that compared with control ovarian cancer cells (SKOV3), mTOR phosphorylation was abnormally activated in cisplatin-resistant ovarian cancer cells (SKOV3/DDP) following cisplatin monotherapy. Treatment with cisplatin combined with DHA could enhance cisplatin-induced proliferation inhibition in SKOV3/DDP cells. This mechanism is at least partially due to DHA deactivation of mTOR kinase and promotion of apoptosis. Although autophagy was also induced by DHA, the reduced cell death was not found by suppressing autophagic flux by Bafilomycin A1 (BAF). Taken together, we conclude that inhibition of cisplatin-induced mTOR activation is one of the main mechanisms by which DHA dramatically promotes its anticancer effect in cisplatin-resistant ovarian cancer cells.

  2. Effects of intra-arterial chemotherapy with a new lipophilic anticancer agent, estradiol-chlorambucil (KM2210), dissolved in lipiodol on experimental liver tumor in rats

    International Nuclear Information System (INIS)

    Anticancer effects and biodistribution of a new lipophilic anticancer agent, estradiol-chlorambucil (KM2210), dissolved in lipiodol (LPD) were investigated as an intra-arterial chemotherapy (IAC) on Walker 256 carcinosarcoma grown in the liver of 136 Wistar rats. All rats treated with KM2210 (10 mg)-LPD survived for 90 days after administration, whereas none of the rats with LPD alone were alive for more than 19 days. Histological examination revealed that there was no viable tumor cell in the encapsulated necrotic tumor at 21 days after administration. There was no significant liver dysfunction or leukopenia due to KM2210. The biodistribution study using [14C, 3H]KM2210-LPD solution showed that KM2210 accumulated selectively in tumor and that the tumor-to-normal-liver and tumor-to-blood ratios were 10 and 1,000, respectively, at 21 days after administration. These results suggest that KM2210 has potential clinical application in the treatment of human liver cancer

  3. PLGA-based microparticles loaded with bacterial-synthesized prodigiosin for anticancer drug release: Effects of particle size on drug release kinetics and cell viability.

    Science.gov (United States)

    Obayemi, J D; Danyuo, Y; Dozie-Nwachukwu, S; Odusanya, O S; Anuku, N; Malatesta, K; Yu, W; Uhrich, K E; Soboyejo, W O

    2016-09-01

    This paper presents the synthesis and physicochemical characterization of biodegradable poly (d,l-lactide-co-glycolide) (PLGA)-based microparticles that are loaded with bacterial-synthesized prodigiosin drug obtained from Serratia marcescens subsp. Marcescens bacteria for controlled anticancer drug delivery. The micron-sized particles were loaded with anticancer drugs [prodigiosin (PG) and paclitaxel (PTX) control] using a single-emulsion solvent evaporation technique. The encapsulation was done in the presence of PLGA (as a polymer matrix) and poly-(vinyl alcohol) (PVA) (as an emulsifier). The effects of processing conditions (on the particle size and morphology) are investigated along with the drug release kinetics and drug-loaded microparticle degradation kinetics. The localization and apoptosis induction by prodigiosin in breast cancer cells is also elucidated along with the reduction in cell viability due to prodigiosin release. The implication of this study is for the potential application of prodigiosin PLGA-loaded microparticles for controlled delivery of cancer drug and treatment to prevent the regrowth or locoregional recurrence, following surgical resection of triple negative breast tumor. PMID:27207038

  4. Dihydroartemisinin potentiates the anticancer effect of cisplatin via mTOR inhibition in cisplatin-resistant ovarian cancer cells: involvement of apoptosis and autophagy

    International Nuclear Information System (INIS)

    Highlights: • Phosphorylation of mTOR is abnormal activation in SKOV3/DDP ovarian cancer cells. • Downregulation of mTOR by DHA helps to sensitize the SKOV3/DDP cells to chemotherapy. • DHA has the potential of induce autophagy in cancer cells. - Abstract: Dihydroartemisinin (DHA) exhibits anticancer activity in tumor cells but its mechanism of action is unclear. Cisplatin (DDP) is currently the best known chemotherapeutic available for ovarian cancer. However, tumors return de novo with acquired resistance over time. Mammalian target of rapamycin (mTOR) is an important kinase that regulates cell apoptosis and autophagy, and its dysregulation has been observed in chemoresistant human cancers. Here, we show that compared with control ovarian cancer cells (SKOV3), mTOR phosphorylation was abnormally activated in cisplatin-resistant ovarian cancer cells (SKOV3/DDP) following cisplatin monotherapy. Treatment with cisplatin combined with DHA could enhance cisplatin-induced proliferation inhibition in SKOV3/DDP cells. This mechanism is at least partially due to DHA deactivation of mTOR kinase and promotion of apoptosis. Although autophagy was also induced by DHA, the reduced cell death was not found by suppressing autophagic flux by Bafilomycin A1 (BAF). Taken together, we conclude that inhibition of cisplatin-induced mTOR activation is one of the main mechanisms by which DHA dramatically promotes its anticancer effect in cisplatin-resistant ovarian cancer cells

  5. The Study on Anti-cancer Effects of Distilling Fresh-ginseng Herbal acupuncture against implanted Sarcoma-180 in vivo and A549 human epithelial lung cancer cells in vitro

    OpenAIRE

    Hae-Young Jang; Ki-Rok Kwon; Hee-Soo Park

    2004-01-01

    Objectives : This study was to investigate the anti-cancer effects of herbal acupuncture with distilled fresh ginseng. The herbal acupuncture was injected to Chung-wan(C.V12) and Wisu(BL21) of mice that were subjected to Sarcoma-180 abdominal cancer cell and A549 human epithelial lung cancer cells in vitro. Methods : Anti-cancer effects of distilled fresh ginseng herbal acupuncture were tested by measruing Cox, Bcl-2, and Bax by using RT-PCR in A549 human epithelial lung cancer cells in v...

  6. Selenoprotein Transcript Level and Enzyme Activity as Biomarkers for Selenium Status and Selenium Requirements in the Turkey (Meleagris gallopavo)

    Science.gov (United States)

    Taylor, Rachel M.; Sunde, Roger A.

    2016-01-01

    The current National Research Council (NRC) selenium (Se) requirement for the turkey is 0.2 μg Se/g diet. The sequencing of the turkey selenoproteome offers additional molecular biomarkers for assessment of Se status. To determine dietary Se requirements using selenoprotein transcript levels and enzyme activities, day-old male turkey poults were fed a Se-deficient diet supplemented with graded levels of Se (0, 0.025, 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, 0.75, 1.0 μg Se/g diet) as selenite, and 12.5X the vitamin E requirement. Poults fed less than 0.05 μg Se/g diet had a significantly reduced rate of growth, indicating the Se requirement for growth in young male poults is 0.05 μg Se/g diet. Se deficiency decreased plasma GPX3 (glutathione peroxidase), liver GPX1, and liver GPX4 activities to 2, 3, and 7%, respectively, of Se-adequate levels. Increasing Se supplementation resulted in well-defined plateaus for all blood, liver and gizzard enzyme activities and mRNA levels, showing that these selenoprotein biomarkers could not be used as biomarkers for supernutritional-Se status. Using selenoenzyme activity, minimum Se requirements based on red blood cell GPX1, plasma GPX3, and pancreas and liver GPX1 activities were 0.29–0.33 μg Se/g diet. qPCR analyses using all 10 dietary Se treatments for all 24 selenoprotein transcripts (plus SEPHS1) in liver, gizzard, and pancreas found that only 4, 4, and 3 transcripts, respectively, were significantly down-regulated by Se deficiency and could be used as Se biomarkers. Only GPX3 and SELH mRNA were down regulated in all 3 tissues. For these transcripts, minimum Se requirements were 0.07–0.09 μg Se/g for liver, 0.06–0.15 μg Se/g for gizzard, and 0.13–0.18 μg Se/g for pancreas, all less than enzyme-based requirements. Panels based on multiple Se-regulated transcripts were effective in identifying Se deficiency. These results show that the NRC turkey dietary Se requirement should be raised to 0.3 μg Se/g diet. PMID

  7. Ultrathin polyaniline film coated on an indium-tin oxide cell-based chip for study of anticancer effect

    International Nuclear Information System (INIS)

    Polyaniline emeraldine base (EB) coated indium-tin oxide (ITO) electrode was prepared for the construction of a cell-based chip. Ultrathin polyaniline PANI film on an ITO was electroactive at neutral pH without co-deposition of an acidic counterion. HeLa cells were cultured on a PANI/ITO substrate and utilized to assess the biological toxicity of anticancer drugs. Cell growth, cell viability and drug-related cell toxicity were evaluated by a cyclic voltammetry (CV) method under a neutral pH. We demonstrated the functionality of a PANI coated ITO electrode for use as a cell chip and found that PANI was a good surface for the HeLa cells to grow without any significant morphological changes.

  8. Anticancer Activities of Brassinosteroids

    Czech Academy of Sciences Publication Activity Database

    Hoffmannová, Lucie; Oklešťková, Jana; Steigerová, J.; Kohout, Ladislav; Kolář, Z.; Strnad, Miroslav

    AG Bussum : Bentham Science, 2012 - (Pereira-Netto, A.), s. 84-93 ISBN 978-1-60805-298-1 Grant ostatní: GA AV ČR(CZ) IAA400550801 Institutional research plan: CEZ:AV0Z50380511 Keywords : antiangiogenic activity * anticancer drugs * apoptosis Subject RIV: CC - Organic Chemistry http://home.ueb.cas.cz/publikace/2012_Strnad_chapter.pdf

  9. Biosynthesis, Antibacterial Activity and Anticancer Effects Against Prostate Cancer (PC-3) Cells of Silver Nanoparticles Using Dimocarpus Longan Lour. Peel Extract.

    Science.gov (United States)

    He, Yan; Du, Zhiyun; Ma, Shijing; Cheng, Shupeng; Jiang, Sen; Liu, Yue; Li, Dongli; Huang, Huarong; Zhang, Kun; Zheng, Xi

    2016-12-01

    Metal nanoparticles, particularly silver nanoparticles (AgNPs), are developing more important roles as diagnostic and therapeutic agents for cancers with the improvement of eco-friendly synthesis methods. This study demonstrates the biosynthesis, antibacterial activity, and anticancer effects of silver nanoparticles using Dimocarpus Longan Lour. peel aqueous extract. The AgNPs were characterized by UV-vis absorption spectroscopy, X-ray diffraction (XRD), high-resolution transmission electron microscopy (HRTEM), scanning electron microscopy (SEM), and Fourier transform infrared spectroscope (FTIR). The bactericidal properties of the synthesized AgNPs were observed via the agar dilution method and the growth inhibition test. The cytotoxicity effect was explored on human prostate cancer PC-3 cells in vitro by trypan blue assay. The expressions of phosphorylated stat 3, bcl-2, survivin, and caspase-3 were examined by Western blot analysis. The longan peel extract acted as a strong reducing and stabilizing agent during the synthesis. Water-soluble AgNPs of size 9-32 nm was gathered with a face-centered cubic structure. The AgNPs had potent bactericidal activities against gram-positive and gram-negative bacteria with a dose-related effect. AgNPs also showed dose-dependent cytotoxicity against PC-3 cells through a decrease of stat 3, bcl-2, and survivin, as well as an increase in caspase-3. These findings confirm the bactericidal properties and explored a potential anticancer application of AgNPs for prostate cancer therapy. Further research should be focused on the comprehensive study of molecular mechanism and in vivo effects on the prostate cancer. PMID:27316741

  10. Anticancer Effects of 1,3-Dihydroxy-2-Methylanthraquinone and the Ethyl Acetate Fraction of Hedyotis Diffusa Willd against HepG2 Carcinoma Cells Mediated via Apoptosis.

    Directory of Open Access Journals (Sweden)

    Yun-Lan Li

    Full Text Available Hedyotis Diffusa Willd, used in Traditional Chinese Medicine, is a treatment for various diseases including cancer, owing to its mild effectiveness and low toxicity. The aim of this study was to identify the main anticancer components in Hedyotis Diffusa Willd, and explore mechanisms underlying their activity. Hedyotis Diffusa Willd was extracted and fractionated using ethyl acetate to obtain the H-Ethyl acetate fraction, which showed higher anticancer activity than the other fractions obtained against HepG2 cells with sulforhodamine B assays. The active component of the H-Ethyl acetate fraction was identified to be 1,3-dihydroxy-2-methylanthraquinone (DMQ with much high inhibitory rate up to 48.9 ± 3.3% and selectivity rate up to 9.4 ± 4.5 folds (p<0.01 at 125 μmol/L. HepG2 cells treated with the fraction and DMQ visualized morphologically using light and fluorescence microscopy. Annexin V--fluorescein isothiocyanate / propidium iodide staining flow cytometry, DNA ladder and cell cycle distribution assays. Mechanistic studies showed up-regulation of caspase-3, -8, and -9 proteases activities (p<0.001, indicating involvement of mitochondrial apoptotic and death receptor pathways. Further studies revealed that reactive oxygen species in DMQ and the fraction treated HepG2 cells increased (p<0.01 while mitochondrial membrane potential reduced significantly (p<0.001 compared to the control by flow cytometry assays. Western blot analysis showed that Bax, p53, Fas, FasL, p21 and cytoplasmic cytochrome C were up-regulated (p<0.01, while Bcl-2, mitochondrial cytochrome C, cyclin E and CDK 2 were down-regulated dose-dependently (p<0.01. The reverse transcriptase-polymerase chain reaction showed that mRNA expressions of p53 and Bax increased (p<0.001 while that of Bcl-2 decreased (p<0.001. Pre-treatment with caspase-8 inhibitor Z-IETD-FMK, or caspase-9 inhibitor Z-LEHD-FMK, attenuated the growth-inhibitory and apoptosis-inducing effects of DMQ and the

  11. CancerHSP: anticancer herbs database of systems pharmacology

    Science.gov (United States)

    Tao, Weiyang; Li, Bohui; Gao, Shuo; Bai, Yaofei; Shar, Piar Ali; Zhang, Wenjuan; Guo, Zihu; Sun, Ke; Fu, Yingxue; Huang, Chao; Zheng, Chunli; Mu, Jiexin; Pei, Tianli; Wang, Yuan; Li, Yan; Wang, Yonghua

    2015-06-01

    The numerous natural products and their bioactivity potentially afford an extraordinary resource for new drug discovery and have been employed in cancer treatment. However, the underlying pharmacological mechanisms of most natural anticancer compounds remain elusive, which has become one of the major obstacles in developing novel effective anticancer agents. Here, to address these unmet needs, we developed an anticancer herbs database of systems pharmacology (CancerHSP), which records anticancer herbs related information through manual curation. Currently, CancerHSP contains 2439 anticancer herbal medicines with 3575 anticancer ingredients. For each ingredient, the molecular structure and nine key ADME parameters are provided. Moreover, we also provide the anticancer activities of these compounds based on 492 different cancer cell lines. Further, the protein targets of the compounds are predicted by state-of-art methods or collected from literatures. CancerHSP will help reveal the molecular mechanisms of natural anticancer products and accelerate anticancer drug development, especially facilitate future investigations on drug repositioning and drug discovery. CancerHSP is freely available on the web at http://lsp.nwsuaf.edu.cn/CancerHSP.php.

  12. Low-Temperature Affected LC-PUFA Conversion and Associated Gene Transcript Level in Nannochioropsis oculata CS-179

    Institute of Scientific and Technical Information of China (English)

    MA Xiaolei; ZHANG Lin; ZHU Baohua; PAN Kehou; LI Si; YANG Guanpin

    2011-01-01

    Nannochloropsis oculata CS-179,a marine eukaryotic unicellular microalga,is rich in long-chain polyunsaturated fatty acids (LC-PUFAs).Culture temperature affected cell growth and the composition of LC-PUFAs.At an initial cell density of 1.5 × 106cell mL-1,the highest growth was observed at 25 ℃ and the cell density reached 3 × 107 cell mL -1 at the beginning of logarithmic phase.The content of LC-PUFAs varied with culture temperature.The highest content of LC-PUFAs (43.96%) and EPA (36.6%) was gained at 20℃.Real-time PCR showed that the abundance of A6-desaturase gene transcripts was significantly different among 5 culture temperatures and the highest transcript level (1 5℃) of Nanoc-D6D took off at cycle 21.45.The gene transcript of C20-elongase gene was higher at lower temperatures (10,15,and 20℃),and the highest transcript level (20℃) of Nanoc-E took off at cycle 21.18.The highest conversion rate (39.3%) of A6-desaturase was also gained at 20℃.But the conversion rate of Nanoc-E was not detected.The higher content of LC-PUFAs was a result of higher gene transcript level and higher enzyme activity.Compared with C20-elongase gene,A6-desaturase gene transcript and enzyme activity varied significantly with temperature.It will be useful to study the mechanism of how the content of LC-PUFAs is affected by temperature.

  13. Bisphenol A alters transcript levels of biomarker genes for Major Depressive Disorder in vascular endothelial cells and colon cancer cells.

    Science.gov (United States)

    Ribeiro-Varandas, Edna; Pereira, H Sofia; Viegas, Wanda; Delgado, Margarida

    2016-06-01

    Bisphenol A (BPA) is capable of mimicking endogenous hormones with potential consequences for human health and BPA exposure has been associated with several human diseases including neuropsychiatric disorders. Here, quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) results show that BPA at low concentrations (10 ng/mL and 1 μg/mL) induces differential transcript levels of four biomarker genes for Major Depressive Disorder (MDD) in HT29 human colon adenocarcinona cell line and Human Umbilical Vein Endothelial Cells (HUVEC). These results substantiate increasing concerns of BPA exposure in levels currently detected in humans. PMID:27010169

  14. Evaluation of anticancer effects of a novel proteasome inhibitor (Velcade), interferon (alpha-interferon) and anti myeloma antibodies on the growth of myeloma cells

    International Nuclear Information System (INIS)

    Cancer is an abnormal growth of cells caused by multiple changes in gene expression leading to deregulated balance of cell proliferation and cell death and ultimately evolving into a population of cells that can invade tissues and metastasize to distant sites, causing significant morbidity. Multiple myeloma (MM) is characterized by the accumulation of malignant plasma cells in the bone marrow leading to impaired hematopoiesis and bone diseases, which includes mainly lytic lesions, pathological fractures, hypercalcaemia and osteoporosis. Chemotherapy is the systemic treatment of cancer with anticancer drugs. Chemotherapy uses powerful drugs that work by slowing or stopping the cancer cells from growing, spreading or multiplying to other parts of the body. Extensive studies were run all over the world during the last years to discovery some new drugs which possess anticancer effect with less toxicity and have the ability to increase the survival time. In the current study Bortezomib was employed as chemotherapeutic drug for the treatment of myeloma cells where a variable dose of Bortezomib (5, 10,20,30,50 and 100 nM/ml) were used for treatment of myeloma cells in vitro. The results obtained indicated that the T.C/ml was decreased by increasing the drug conc. compared to that of control group. These results illustrated the effect of Bortezomib on the growth of myeloma cells, where the myeloma cell division was decreased while the older cells were deteriorated so that the T.C/ml were decreased. Also the viability of myeloma cells were significantly decreased after 72 hours of addition at drug concentration 20, 30, 50 and 100 nM/ml).

  15. Anticancer properties of lamellarins.

    Science.gov (United States)

    Bailly, Christian

    2015-03-01

    In 1985 the first lamellarins were isolated from a small oceanic sea snail. Today, more than 50 lamellarins have been inventoried and numerous derivatives synthesized and tested as antiviral or anticancer agents. The lead compound in the family is lamellarin D, characterized as a potent inhibitor of both nuclear and mitochondrial topoisomerase I but also capable of directly interfering with mitochondria to trigger cancer cell death. The pharmacology and chemistry of lamellarins are discussed here and the mechanistic portrait of lamellarin D is detailed. Lamellarins frequently serve as a starting point in the design of anticancer compounds. Extensive efforts have been devoted to create novel structures as well as to improve synthetic methods, leading to lamellarins and related pyrrole-derived marine alkaloids. PMID:25706633

  16. Anticancer Properties of Lamellarins

    Directory of Open Access Journals (Sweden)

    Christian Bailly

    2015-02-01

    Full Text Available In 1985 the first lamellarins were isolated from a small oceanic sea snail. Today, more than 50 lamellarins have been inventoried and numerous derivatives synthesized and tested as antiviral or anticancer agents. The lead compound in the family is lamellarin D, characterized as a potent inhibitor of both nuclear and mitochondrial topoisomerase I but also capable of directly interfering with mitochondria to trigger cancer cell death. The pharmacology and chemistry of lamellarins are discussed here and the mechanistic portrait of lamellarin D is detailed. Lamellarins frequently serve as a starting point in the design of anticancer compounds. Extensive efforts have been devoted to create novel structures as well as to improve synthetic methods, leading to lamellarins and related pyrrole-derived marine alkaloids.

  17. Anticancer Properties of Lamellarins

    OpenAIRE

    Christian Bailly

    2015-01-01

    In 1985 the first lamellarins were isolated from a small oceanic sea snail. Today, more than 50 lamellarins have been inventoried and numerous derivatives synthesized and tested as antiviral or anticancer agents. The lead compound in the family is lamellarin D, characterized as a potent inhibitor of both nuclear and mitochondrial topoisomerase I but also capable of directly interfering with mitochondria to trigger cancer cell death. The pharmacology and chemistry of lamellarins are discussed ...

  18. Transcript level coordination of carbon pathways during silicon starvation-induced lipid accumulation in the diatom Thalassiosira pseudonana.

    Science.gov (United States)

    Smith, Sarah R; Glé, Corine; Abbriano, Raffaela M; Traller, Jesse C; Davis, Aubrey; Trentacoste, Emily; Vernet, Maria; Allen, Andrew E; Hildebrand, Mark

    2016-05-01

    Diatoms are one of the most productive and successful photosynthetic taxa on Earth and possess attributes such as rapid growth rates and production of lipids, making them candidate sources of renewable fuels. Despite their significance, few details of the mechanisms used to regulate growth and carbon metabolism are currently known, hindering metabolic engineering approaches to enhance productivity. To characterize the transcript level component of metabolic regulation, genome-wide changes in transcript abundance were documented in the model diatom Thalassiosira pseudonana on a time-course of silicon starvation. Growth, cell cycle progression, chloroplast replication, fatty acid composition, pigmentation, and photosynthetic parameters were characterized alongside lipid accumulation. Extensive coordination of large suites of genes was observed, highlighting the existence of clusters of coregulated genes as a key feature of global gene regulation in T. pseudonana. The identity of key enzymes for carbon metabolic pathway inputs (photosynthesis) and outputs (growth and storage) reveals these clusters are organized to synchronize these processes. Coordinated transcript level responses to silicon starvation are probably driven by signals linked to cell cycle progression and shifts in photophysiology. A mechanistic understanding of how this is accomplished will aid efforts to engineer metabolism for development of algal-derived biofuels. PMID:26844818

  19. A hairpin within YAP mRNA 3'UTR functions in regulation at post-transcription level.

    Science.gov (United States)

    Gao, Yuen; Wang, Yuan; Feng, Jinyan; Feng, Guoxing; Zheng, Minying; Yang, Zhe; Xiao, Zelin; Lu, Zhanping; Ye, Lihong; Zhang, Xiaodong

    2015-04-01

    The central dogma of gene expression is that DNA is transcribed into messenger RNAs, which in turn serve as the template for protein synthesis. Recently, it has been reported that mRNAs display regulatory roles that rely on their ability to compete for microRNA binding, independent of their protein-coding function. However, the regulatory mechanism of mRNAs remains poorly understood. Here, we report that a hairpin within YAP mRNA 3'untranslated region (3'UTR) functions in regulation at post-transcription level through generating endogenous siRNAs (esiRNAs). Bioinformatics analysis for secondary structure showed that YAP mRNA displayed a hairpin structure (termed standard hairpin, S-hairpin) within its 3'UTR. Surprisingly, we observed that the overexpression of S-hairpin derived from YAP 3'UTR (YAP-sh) increased the luciferase reporter activities of transcriptional factor NF-κB and AP-1 in 293T cells. Moreover, we identified that a fragment from YAP-sh, an esiRNA, was able to target mRNA 3'UTR of NF2 (a member of Hippo-signaling pathway) and YAP mRNA 3'UTR itself in hepatoma cells. Thus, we conclude that the YAP-sh within YAP mRNA 3'UTR may serve as a novel regulatory element, which functions in regulation at post-transcription level. Our finding provides new insights into the mechanism of mRNAs in regulatory function. PMID:25727017

  20. Sesterterpenoids with Anticancer Activity.

    Science.gov (United States)

    Evidente, Antonio; Kornienko, Alexander; Lefranc, Florence; Cimmino, Alessio; Dasari, Ramesh; Evidente, Marco; Mathieu, Véronique; Kiss, Robert

    2015-01-01

    Terpenes have received a great deal of attention in the scientific literature due to complex, synthetically challenging structures and diverse biological activities associated with this class of natural products. Based on the number of C5 isoprene units they are generated from, terpenes are classified as hemi- (C5), mono- (C10), sesqui- (C15), di- (C20), sester- (C25), tri (C30), and tetraterpenes (C40). Among these, sesterterpenes and their derivatives known as sesterterpenoids, are ubiquitous secondary metabolites in fungi, marine organisms, and plants. Their structural diversity encompasses carbotricyclic ophiobolanes, polycyclic anthracenones, polycyclic furan-2-ones, polycyclic hydroquinones, among many other carbon skeletons. Furthermore, many of them possess promising biological activities including cytotoxicity and the associated potential as anticancer agents. This review discusses the natural sources that produce sesterterpenoids, provides sesterterpenoid names and their chemical structures, biological properties with the focus on anticancer activities and literature references associated with these metabolites. A critical summary of the potential of various sesterterpenoids as anticancer agents concludes the review. PMID:26295461

  1. In silico identification of anti-cancer compounds and plants from traditional Chinese medicine database

    OpenAIRE

    Shao-Xing Dai; Wen-Xing Li; Fei-Fei Han; Yi-Cheng Guo; Jun-Juan Zheng; Jia-Qian Liu; Qian Wang; Yue-Dong Gao; Gong-Hua Li; Jing-Fei Huang

    2016-01-01

    There is a constant demand to develop new, effective, and affordable anti-cancer drugs. The traditional Chinese medicine (TCM) is a valuable and alternative resource for identifying novel anti-cancer agents. In this study, we aim to identify the anti-cancer compounds and plants from the TCM database by using cheminformatics. We first predicted 5278 anti-cancer compounds from TCM database. The top 346 compounds were highly potent active in the 60 cell lines test. Similarity analysis revealed t...

  2. Use of metformin alone is not associated with survival outcomes of colorectal cancer cell but AMPK activator AICAR sensitizes anticancer effect of 5-fluorouracil through AMPK activation.

    Directory of Open Access Journals (Sweden)

    Xinbing Sui

    Full Text Available Colorectal cancer (CRC is still the third most common cancer and the second most common causes of cancer-related death around the world. Metformin, a biguanide, which is widely used for treating diabetes mellitus, has recently been shown to have a suppressive effect on CRC risk and mortality, but not all laboratory studies suggest that metformin has antineoplastic activity. Here, we investigated the effect of metformin and AMPK activator AICAR on CRC cells proliferation. As a result, metformin did not inhibit cell proliferation or induce apoptosis for CRC cell lines in vitro and in vivo. Different from metformin, AICAR emerged antitumor activity and sensitized anticancer effect of 5-FU on CRC cells in vitro and in vivo. In further analysis, we show that AMPK activation may be a key molecular mechanism for the additive effect of AICAR. Taken together, our results suggest that metformin has not antineoplastic activity for CRC cells as a single agent but AMPK activator AICAR can induce apoptosis and enhance the cytotoxic effect of 5-FU through AMPK activation.

  3. 3-Bromopyruvate (3BP) a fast acting, promising, powerful, specific, and effective "small molecule" anti-cancer agent taken from labside to bedside: introduction to a special issue.

    Science.gov (United States)

    Pedersen, Peter L

    2012-02-01

    Although the "Warburg effect", i.e., elevated glucose metabolism to lactic acid (glycolysis) even in the presence of oxygen, has been recognized as the most common biochemical phenotype of cancer for over 80 years, its biochemical and genetic basis remained unknown for over 50 years. Work focused on elucidating the underlying mechanism(s) of the "Warburg effect" commenced in the author's laboratory in 1969. By 1985 among the novel findings made two related most directly to the basis of the "Warburg effect", the first that the mitochondrial content of tumors exhibiting this phenotype is markedly decreased relative to the tissue of origin, and the second that such mitochondria have markedly elevated amounts of the enzyme hexokinase-2 (HK2) bound to their outer membrane. HK2 is the first of a number of enzymes in cancer cells involved in metabolizing the sugar glucose to lactic acid. At its mitochondrial location HK2 binds at/near the protein VDAC (voltage dependent anion channel), escapes inhibition by its product glucose-6-phosphate, and gains access to mitochondrial produced ATP. As shown by others, it also helps immortalize cancer cells, i.e., prevents cell death. Based on these studies, the author's laboratory commenced experiments to elucidate the gene basis for the overexpression of HK2 in cancer. These studies led to both the discovery of a unique HK2 promoter region markedly activated by both hypoxic conditions and moderately activated by several metabolites (e.g., glucose), Also discovered was the promoter's regulation by epigenetic events (i.e., methylation, demethylation). Finally, the author's laboratory turned to the most important objective. Could they selectively and completely destroy cancerous tumors in animals? This led to the discovery in an experiment conceived, designed, and conducted by Young Ko that the small molecule 3-bromopyruvate (3BP), the subject of this mini-review series, is an incredibly powerful and swift acting anticancer agent

  4. Specific internalization and synergistic anticancer effect of docetaxel-encapsulated chitosan-modified polymeric nanocarriers: a novel approach in cancer chemotherapy

    International Nuclear Information System (INIS)

    Nanocarriers can be surface engineered to increase endocytosis for applications in delivery of chemotherapeutics. This study investigated the chitosan (CS)-mediated effects on the anticancer efficacy and uptake of docetaxel-loaded nanometric particles (5-fold) in intracellular uptake as well as antitumor efficacy of modified nanoparticles (NPs) that explicate the possibility of saccharide marker-mediated tumor targeting along with synergism via proapoptotic effect of CS. Additionally, high positivity of optimized tailored nanocarrier (+23.3 ± 2.02 mV, 242.8 ± 9.42 nm) may have accounted for the increased adsorption-mediated endocytosis, preferably toward tumor cells with negative potential. Developed drug carrier system showed high stability in human blood which is in compliance with mucoadhesive property of CS. Transmission electron microscopy technique was applied to observe shape and morphological features of NPs. Furthermore, in vivo tissue toxicity study revealed safe use of drug at 20 mg/kg dose in nanoparticulate form. Moreover, the enhanced in vitro uptake of these NPs and their cytotoxicity against the tumor cells along with synergistic effect of CS clearly suggest that CS-modified carrier system is a promising candidate for preclinical studies to achieve wider anti-tumor therapeutic window and lower side effects

  5. A hairpin within YAP mRNA 3′UTR functions in regulation at post-transcription level

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Yuen; Wang, Yuan; Feng, Jinyan; Feng, Guoxing; Zheng, Minying; Yang, Zhe; Xiao, Zelin; Lu, Zhanping [State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071 (China); Ye, Lihong [State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071 (China); Zhang, Xiaodong, E-mail: zhangxd@nankai.edu.cn [State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071 (China)

    2015-04-03

    The central dogma of gene expression is that DNA is transcribed into messenger RNAs, which in turn serve as the template for protein synthesis. Recently, it has been reported that mRNAs display regulatory roles that rely on their ability to compete for microRNA binding, independent of their protein-coding function. However, the regulatory mechanism of mRNAs remains poorly understood. Here, we report that a hairpin within YAP mRNA 3′untranslated region (3′UTR) functions in regulation at post-transcription level through generating endogenous siRNAs (esiRNAs). Bioinformatics analysis for secondary structure showed that YAP mRNA displayed a hairpin structure (termed standard hairpin, S-hairpin) within its 3′UTR. Surprisingly, we observed that the overexpression of S-hairpin derived from YAP 3′UTR (YAP-sh) increased the luciferase reporter activities of transcriptional factor NF-κB and AP-1 in 293T cells. Moreover, we identified that a fragment from YAP-sh, an esiRNA, was able to target mRNA 3′UTR of NF2 (a member of Hippo-signaling pathway) and YAP mRNA 3′UTR itself in hepatoma cells. Thus, we conclude that the YAP-sh within YAP mRNA 3′UTR may serve as a novel regulatory element, which functions in regulation at post-transcription level. Our finding provides new insights into the mechanism of mRNAs in regulatory function. - Highlights: • An S-hairpin within YAP mRNA 3′UTR possesses regulatory function. • YAP-sh acts as a regulatory element for YAP at post-transcription level. • YAP-sh-3p20, an esiRNA derived from YAP-sh, targets mRNAs of YAP and NF2. • YAP-sh-3p20 depresses the proliferation of HepG2 cells in vitro.

  6. A hairpin within YAP mRNA 3′UTR functions in regulation at post-transcription level

    International Nuclear Information System (INIS)

    The central dogma of gene expression is that DNA is transcribed into messenger RNAs, which in turn serve as the template for protein synthesis. Recently, it has been reported that mRNAs display regulatory roles that rely on their ability to compete for microRNA binding, independent of their protein-coding function. However, the regulatory mechanism of mRNAs remains poorly understood. Here, we report that a hairpin within YAP mRNA 3′untranslated region (3′UTR) functions in regulation at post-transcription level through generating endogenous siRNAs (esiRNAs). Bioinformatics analysis for secondary structure showed that YAP mRNA displayed a hairpin structure (termed standard hairpin, S-hairpin) within its 3′UTR. Surprisingly, we observed that the overexpression of S-hairpin derived from YAP 3′UTR (YAP-sh) increased the luciferase reporter activities of transcriptional factor NF-κB and AP-1 in 293T cells. Moreover, we identified that a fragment from YAP-sh, an esiRNA, was able to target mRNA 3′UTR of NF2 (a member of Hippo-signaling pathway) and YAP mRNA 3′UTR itself in hepatoma cells. Thus, we conclude that the YAP-sh within YAP mRNA 3′UTR may serve as a novel regulatory element, which functions in regulation at post-transcription level. Our finding provides new insights into the mechanism of mRNAs in regulatory function. - Highlights: • An S-hairpin within YAP mRNA 3′UTR possesses regulatory function. • YAP-sh acts as a regulatory element for YAP at post-transcription level. • YAP-sh-3p20, an esiRNA derived from YAP-sh, targets mRNAs of YAP and NF2. • YAP-sh-3p20 depresses the proliferation of HepG2 cells in vitro

  7. Anti-Cancer Effect of Metabotropic Glutamate Receptor 1 Inhibition in Human Glioma U87 Cells: Involvement of PI3K/Akt/mTOR Pathway

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    Chi Zhang

    2015-01-01

    Full Text Available Background: Metabotropic glutamate receptors (mGluRs are G-protein-coupled receptors that mediate neuronal excitability and synaptic plasticity in the central nervous system, and emerging evidence suggests a role of mGluRs in the biology of cancer. Previous studies showed that mGluR1 was a potential therapeutic target for the treatment of breast cancer and melanoma, but its role in human glioma has not been determined. Methods: In the present study, we investigated the effects of mGluR1 inhibition in human glioma U87 cells using specific targeted small interfering RNA (siRNA or selective antagonists Riluzole and BAY36-7620. The anti-cancer effects of mGluR1 inhibition were measured by cell viability, lactate dehydrogenase (LDH release, TUNEL staining, cell cycle assay, cell invasion and migration assays in vitro, and also examined in a U87 xenograft model in vivo. Results: Inhibition of mGluR1 significantly decreased the cell viability but increased the LDH release in a dose-dependent fashion in U87 cells. These effects were accompanied with the induction of caspase-dependent apoptosis and G0/G1 cell cycle arrest. In addition, the results of Matrigel invasion and cell tracking assays showed that inhibition of mGluR1 apparently attenuated cell invasion and migration in U87 cells. All these anti-cancer effects were ablated by the mGluR1 agonist L-quisqualic acid. The results of western blot analysis showed that mGluR1 inhibition overtly decreased the phosphorylation of PI3K, Akt, mTOR and P70S6K, indicating the mitigated activation of PI3K/Akt/mTOR pathway. Moreover, the anti-tumor activity of mGluR1 inhibition in vivo was also demonstrated in a U87 xenograft glioma model in athymic nude mice. Conclusion: The remarkable efficiency of mGluR1 inhibition to induce cell death in U87 cells may find therapeutic application for the treatment of glioma patients.

  8. Survivin knockdown increased anti-cancer effects of (-)-epigallocatechin-3-gallate in human malignant neuroblastoma SK-N-BE2 and SH-SY5Y cells

    Energy Technology Data Exchange (ETDEWEB)

    Hossain, Md. Motarab [Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, SC (United States); Banik, Naren L. [Department of Neurosciences, Medical University of South Carolina, Charleston, SC (United States); Ray, Swapan K., E-mail: swapan.ray@uscmed.sc.edu [Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, SC (United States)

    2012-08-01

    network formation ability of cells was significantly inhibited by survivin silencing and completely by combination of survivin silencing and EGCG treatment. Collectively, survivin silencing potentiated anti-cancer effects of EGCG in human malignant neuroblastoma cells having survivin overexpression. -- Highlights: Black-Right-Pointing-Pointer Survivin shRNA + EGCG controlled growth of human malignant neuroblastoma cells. Black-Right-Pointing-Pointer Survivin knockdown induced neuronal differentiation in neuroblastoma cells. Black-Right-Pointing-Pointer Survivin shRNA + EGCG induced morphological and biochemical features of apoptosis. Black-Right-Pointing-Pointer Combination therapy inhibited invasion, proliferation, and angiogenesis as well. Black-Right-Pointing-Pointer So, combination therapy showed multiple anti-cancer mechanisms in neuroblastoma.

  9. Anticancer activity of an extract from needles and twigs of Taxus cuspidata and its synergistic effect as a cocktail with 5-fluorouracil

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    Shang Weihu

    2011-12-01

    Full Text Available Abstract Background Botanical medicines are increasingly combined with chemotherapeutics as anticancer drug cocktails. This study aimed to assess the chemotherapeutic potential of an extract of Taxus cuspidata (TC needles and twigs produced by artificial cuttage and its co-effects as a cocktail with 5-fluorouracil (5-FU. Methods Components of TC extract were identified by HPLC fingerprinting. Cytotoxicity analysis was performed by MTT assay or ATP assay. Apoptosis studies were analyzed by H & E, PI, TUNEL staining, as well as Annexin V/PI assay. Cell cycle analysis was performed by flow cytometry. 5-FU concentrations in rat plasma were determined by HPLC and the pharmacokinetic parameters were estimated using 3p87 software. Synergistic efficacy was subjected to median effect analysis with the mutually nonexclusive model using Calcusyn1 software. The significance of differences between values was estimated by using a one-way ANOVA. Results TC extract reached inhibition rates of 70-90% in different human cancer cell lines (HL-60, BGC-823, KB, Bel-7402, and HeLa but only 5-7% in normal mouse T/B lymphocytes, demonstrating the broad-spectrum anticancer activity and low toxicity to normal cells of TC extract in vitro. TC extract inhibited cancer cell growth by inducing apoptosis and G2/M cell cycle arrest. Most interestingly, TC extract and 5-FU, combined as a cocktail, synergistically inhibited the growth of cancer cells in vitro, with Combination Index values (CI ranging from 0.90 to 0.26 at different effect levels from IC50 to IC90 in MCF-7 cells, CI ranging from 0.93 to 0.13 for IC40 to IC90 in PC-3M-1E8 cells, and CI TC extract did not affect the pharmacokinetics of 5-FU in rats. Conclusions The combinational use of the TC extract with 5-FU displays strong cytotoxic synergy in cancer cells and low cytotoxicity in normal cells. These findings suggest that this cocktail may have a potential role in cancer treatment.

  10. Simulation Model Based on Non-Newtonian Fluid Mechanics Applied to the Evaluation of the Embolic Effect of Emulsions of Iodized Oil and Anticancer Drug

    International Nuclear Information System (INIS)

    Purpose: To verify the difference in embolic effect between oil-in-water (O-W) and water-in-oil (W-O) emulsions composed of iodized oil and an anticancer drug, epirubicin, using a simulation model based on non-Newtonian fluid mechanics.Methods: Flow curves of pure iodized oil and two types of O-W and W-O emulsions immediately and 1 hr after preparation were examined with a viscometer. Using the yield stress data obtained, we simulated the stagnation of each fluid with steady flow in a rigid tube.Results: The W-O emulsions were observed to stagnate in the thin tube at a low pressure gradient. However, the embolic effect of the W-O emulsions decreased 1 hr after preparation. The O-W emulsions were stable and did not stagnate under the conditions in which the W-O emulsions stagnated.Conclusion: The simulation model showed that the embolic effect of the W-O emulsions was superior to that of the O-W emulsions

  11. Anticancer Effect of Fucoidan on DU-145 Prostate Cancer Cells through Inhibition of PI3K/Akt and MAPK Pathway Expression

    Science.gov (United States)

    Choo, Gang-Sik; Lee, Hae-Nim; Shin, Seong-Ah; Kim, Hyeong-Jin; Jung, Ji-Youn

    2016-01-01

    In this study, we showed that PI3K/Akt signaling mediates fucoidan’s anticancer effects on prostate cancer cells, including suppression of proliferation. Fucoidan significantly decreased viability of DU-145 cancer cells in a concentration-dependent manner as shown by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The drug also significantly increased chromatin condensation, which indicates apoptosis, in a concentration-dependent manner as shown by DAPI (4′,6-diamidino-2-phenylindole) staining. Fucoidan increased expression of Bax, cleaved poly-ADP ribose polymerase and cleaved caspase-9, and decreased of the Bcl-2, p-Akt, p-PI3K, p-P38, and p-ERK in a concentration-dependent manner. In vivo, fucoidan (at 5 and 10 mg/kg) significantly decreased tumor volume, and increased apoptosis as assessed by the TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay, confirming the tumor inhibitory effect. The drug also increased expression of p-Akt and p-ERK as shown by immunohistochemistry staining. Therefore, fucoidan may be a promising cancer preventive medicine due to its growth inhibitory effects and induction of apoptosis in human prostate cancer cells. PMID:27399727

  12. Anticancer Effects of Paris Saponins by Apoptosis and PI3K/AKT Pathway in Gefitinib-Resistant Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Zhu, XinHai; Jiang, Hao; Li, Jinhui; Xu, Ji; Fei, Zhenghua

    2016-01-01

    BACKGROUND Paris saponins have been studied for their anticancer effects in various cancer types, but the mechanisms underlying the cytotoxic effects, especially in EGFR-TKI-resistant cells, are still unclear. We explored the potential mechanism of the antitumor effects of PSI, II, VI, VII in EGFR-TKI-resistant cells and attempted to develop PSI, II, VI, VII as a systemic treatment strategy for EGFR-TKI-resistant lung cancer. MATERIAL AND METHODS Growth inhibition was detected by MTT assay. The apoptosis assay was detected using annexin-V/PI and Hoechst staining. The level of PI3K, pAKT, Bax, Bcl-2, caspase-3, and caspase-9 protein expression were detected using Western blot analysis. RESULTS The results revealed that PSI, II, VI, VII inhibited the proliferation of PC-9-ZD cells. Furthermore, PSI, II, VI, VII induced significant cell apoptosis. The levels of PI3K, pAKT, Bcl-2 protein decreased, while the Bax, caspase-3, and caspase-9 protein was increased by PSI, II, PSVI, PSVII treatment and resulted in increased sensitivity to gefitinib in PC-9-ZD cells. CONCLUSIONS The underlying mechanism of Paris saponins may be related to targeting the PI3K/AKT pathways to cause apoptosis. Our results suggest a therapeutic potential of Paris saponins in clinical settings for gefitinib-resistant NSCLC. PMID:27125283

  13. Dynamic modeling of bone metastasis, microenvironment and therapy: Integrating parathyroid hormone (PTH) effect, anti-resorptive and anti-cancer therapy.

    Science.gov (United States)

    Coelho, Rui Moura; Lemos, João Miranda; Alho, Irina; Valério, Duarte; Ferreira, Arlindo R; Costa, Luís; Vinga, Susana

    2016-02-21

    Bone is a common site for the development of metastasis, as its microenvironment provides the necessary conditions for the growth and proliferation of cancer cells. Several mathematical models to describe the bone remodeling process and how osteoclasts and osteoblasts coupled action ensures bone homeostasis have been proposed and further extended to include the effect of cancer cells. The model proposed here includes the influence of the parathyroid hormone (PTH) as capable of triggering and regulating the bone remodeling cycle. It also considers the secretion of PTH-related protein (PTHrP) by cancer cells, which stimulates the production of receptor activator of nuclear factor kappa-B ligand (RANKL) by osteoblasts that activates osteoclasts, increasing bone resorption and the subsequent release of growth factors entrapped in the bone matrix, which induce tumor growth, giving rise to a self-perpetuating cycle known as the vicious cycle of bone metastases. The model additionally describes how the presence of metastases contributes to the decoupling between bone resorption and formation. Moreover, the effects of anti-cancer and anti-resorptive treatments, through chemotherapy and the administration of bisphosphonates or denosumab, are also included, along with their corresponding pharmacokinetics (PK) and pharmacodynamics (PD). The simulated models, available at http://sels.tecnico.ulisboa.pt/software/, are able to describe bone remodeling cycles, the growth of bone metastases and how treatment can effectively reduce tumor burden on bone and prevent loss of bone strength. PMID:26657065

  14. Screening for impact of popular herbs improving mental abilities on the transcriptional level of brain transporters

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    Mrozikiewicz Przemyslaw M.

    2014-06-01

    Full Text Available There are a number of compounds that can modify the activity of ABC (ATP-binding cassette and SLC (solute carrier transporters in the blood-brain barrier (BBB. The aim of this study was to investigate the effect of natural and synthetic substances on the expression level of genes encoding transporters present in the BBB (mdr1a, mdr1b, mrp1, mrp2, oatp1a4, oatp1a5 and oatp1c1. Our results showed that verapamil caused the greatest reduction in the mRNA level while other synthetic (piracetam, phenobarbital and natural (codeine, cyclosporine A, quercetin substances showed a selective inhibitory effect. Further, the extract from the roots of Panax ginseng C. A. Meyer exhibited a decrease of transcription against selected transporters whereas the extract from Ginkgo biloba L. leaves resulted in an increase of the expression level of tested genes, except for mrp2. Extract from the aerial parts of Hypericum perforatum L. was the only one to cause an increased mRNA level for mdr1 and oatp1c1. These findings suggest that herbs can play an important role in overcoming the BBB and multidrug resistance to pharmacotherapy of brain cancer and mental disorders, based on the activity of selected drug-metabolizing enzymes and transporters located in the BBB

  15. High ACSL5 transcript levels associate with systemic lupus erythematosus and apoptosis in Jurkat T lymphocytes and peripheral blood cells.

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    Antonio Catalá-Rabasa

    Full Text Available BACKGROUND: Systemic lupus erythematosus (SLE is a prototypical autoimmune disease in which increased apoptosis and decreased apoptotic cells removal has been described as most relevant in the pathogenesis. Long-chain acyl-coenzyme A synthetases (ACSLs have been involved in the immunological dysfunction of mouse models of lupus-like autoimmunity and apoptosis in different in vitro cell systems. The aim of this work was to assess among the ACSL isoforms the involvement of ACSL2, ACSL4 and ACSL5 in SLE pathogenesis. FINDINGS: With this end, we determined the ACSL2, ACSL4 and ACSL5 transcript levels in peripheral blood mononuclear cells (PBMCs of 45 SLE patients and 49 healthy controls by quantitative real time-PCR (q-PCR. We found that patients with SLE had higher ACSL5 transcript levels than healthy controls [median (range, healthy controls = 16.5 (12.3-18.0 vs. SLE = 26.5 (17.8-41.7, P = 3.9×10 E-5] but no differences were found for ACSL2 and ACSL4. In in vitro experiments, ACSL5 mRNA expression was greatly increased when inducing apoptosis in Jurkat T cells and PBMCs by Phorbol-Myristate-Acetate plus Ionomycin (PMA+Io. On the other hand, short interference RNA (siRNA-mediated silencing of ACSL5 decreased induced apoptosis in Jurkat T cells up to the control levels as well as decreased mRNA expression of FAS, FASLG and TNF. CONCLUSIONS: These findings indicate that ACSL5 may play a role in the apoptosis that takes place in SLE. Our results point to ACSL5 as a potential novel functional marker of pathogenesis and a possible therapeutic target in SLE.

  16. Antroquinonol displays anticancer potential against human hepatocellular carcinoma cells: a crucial role of AMPK and mTOR pathways.

    Science.gov (United States)

    Chiang, Po-Cheng; Lin, Ssu-Chia; Pan, Shiow-Lin; Kuo, Ching-Hua; Tsai, I-Lin; Kuo, Mao-Tien; Wen, Wu-Che; Chen, Peini; Guh, Jih-Hwa

    2010-01-15

    5'AMP-activated protein kinase (AMPK) and the mammalian target of rapamycin (mTOR) are two serine/threonine protein kinases responsible for cellular energy homeostasis and translational control, respectively. Evidence suggests that these two kniases are potential targets for cancer chemotherapy against hepatocellular carcinoma (HCC). Antroquinonol that is isolated from Antrodia camphorate, a well-known Traditional Chinese Medicine for treatment of liver diseases, displayed effective anticancer activity against both HBV DNA-positive and -negative HCC cell lines. The rank order of potency against HCCs is HepG2>HepG2.2.15>Mahlavu>PLC/PRF/5>SK-Hep1>Hep3B. Antroquinonol completely abolished cell-cycle progression released from double-thymidine-block synchronization and caused a subsequent apoptosis. The data were supported by down-regulation and reduced nuclear translocation of G1-regulator proteins, including cyclin D1, cyclin E, Cdk4 and Cdk2. Further analysis showed that the mRNA expressions of the G1-regulator proteins were not modified by antroquinonol, indicating an inhibition of translational but not transcriptional levels. Antroquinonol induced the assembly of tuberous sclerosis complex (TSC)-1/TSC2, leading to the blockade of cellular protein synthesis through inhibition of protein phosphorylation including mTOR (Ser(2448)), p70(S6K) (Thr(421)/Ser(424) and Thr(389)) and 4E-BP1 (Thr(37)/Thr(46) and Thr(70)). Furthermore, the AMPK activity was elevated by antroquinonol. Compound C, a selective AMPK inhibitor, significantly reversed antroquinonol-mediated effects suggesting the crucial role of AMPK. Besides, the loss of mitochondrial membrane potential and depletion of mitochondrial content indicated the mitochondrial stress caused by antroquinonol. In summary, the data suggest that antroquinonol displays anticancer activity against HCCs through AMPK activation and inhibition of mTOR translational pathway, leading to G1 arrest of the cell-cycle and subsequent cell

  17. Deciphering Mineral Homeostasis in Barley Seed Transfer Cells at Transcriptional Level.

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    Behrooz Darbani

    Full Text Available In addition to the micronutrient inadequacy of staple crops for optimal human nutrition, a global downtrend in crop-quality has emerged from intensive breeding for yield. This trend will be aggravated by elevated levels of the greenhouse gas carbon dioxide. Therefore, crop biofortification is inevitable to ensure a sustainable supply of minerals to the large part of human population who is dietary dependent on staple crops. This requires a thorough understanding of plant-mineral interactions due to the complexity of mineral homeostasis. Employing RNA sequencing, we here communicate transfer cell specific effects of excess iron and zinc during grain filling in our model crop plant barley. Responding to alterations in mineral contents, we found a long range of different genes and transcripts. Among them, it is worth to highlight the auxin and ethylene signaling factors Arfs, Abcbs, Cand1, Hps4, Hac1, Ecr1, and Ctr1, diurnal fluctuation components Sdg2, Imb1, Lip1, and PhyC, retroelements, sulfur homeostasis components Amp1, Hmt3, Eil3, and Vip1, mineral trafficking components Med16, Cnnm4, Aha2, Clpc1, and Pcbps, and vacuole organization factors Ymr155W, RabG3F, Vps4, and Cbl3. Our analysis introduces new interactors and signifies a broad spectrum of regulatory levels from chromatin remodeling to intracellular protein sorting mechanisms active in the plant mineral homeostasis. The results highlight the importance of storage proteins in metal ion toxicity-resistance and chelation. Interestingly, the protein sorting and recycling factors Exoc7, Cdc1, Sec23A, and Rab11A contributed to the response as well as the polar distributors of metal-transporters ensuring the directional flow of minerals. Alternative isoform switching was found important for plant adaptation and occurred among transcripts coding for identical proteins as well as transcripts coding for protein isoforms. We also identified differences in the alternative-isoform preference between

  18. Transcript level of AKR1C3 is down-regulated in gastric cancer.

    Science.gov (United States)

    Frycz, Bartosz Adam; Murawa, Dawid; Borejsza-Wysocki, Maciej; Wichtowski, Mateusz; Spychała, Arkadiusz; Marciniak, Ryszard; Murawa, Paweł; Drews, Michał; Jagodziński, Paweł Piotr

    2016-04-01

    Steroid hormones have been shown to play a role in gastric carcinogenesis. Large amounts of steroid hormones are locally produced in the peripheral tissues of both genders. Type 5 of 17β-hydroxysteroid dehydrogenase, encoded by the AKR1C3 gene, plays a pivotal role in both androgen and estrogen metabolism, and its expression was found to be deregulated in different cancers. In this study we measured AKR1C3 transcript and protein levels in nontumoral and primary tumoral gastric tissues, and evaluated their association with some clinicopathological features of gastric cancer (GC). We found decreased levels of AKR1C3 transcript (p T3, T4, and G3 grades. We also determined the effect of the histone deacetylase inhibitor sodium butyrate (NaBu) on AKR1C3 expression in EPG 85-257 and HGC-27 GC cell lines. We found that NaBu elevates the levels of both AKR1C3 transcript and protein in the cell lines we investigated. Together, our results suggest that decreased expression of AKR1C3 may be involved in development of GC and can be restored by NaBu. PMID:27019068

  19. Regulation of nucleus accumbens transcript levels in mice by early-life social stress and cocaine.

    Science.gov (United States)

    Lo Iacono, Luisa; Valzania, Alessandro; Visco-Comandini, Federica; Viscomi, Maria Teresa; Felsani, Armando; Puglisi-Allegra, Stefano; Carola, Valeria

    2016-04-01

    Much interest has been piqued regarding the quality of one's environment at early ages in modulating the susceptibility to drug addiction in adulthood. However, the molecular mechanisms that are engaged during early trauma and mediate the risk for drug addiction are poorly understood. In rodents, exposure to early-life stress alters the rewarding effects of cocaine, amphetamine, and morphine in adulthood. Recently, we demonstrated that the exposure of juvenile mice to social threat (Social Stress, S-S) promoted cocaine-seeking behavior and relapse of cocaine-seeking after periods of withdrawal, compared with unhandled controls (UN) and with juvenile mice that experienced only daily isolation in a novel environment (no social stress, NS-S). Interestingly, while the exposure to NS-S slightly increased cocaine-seeking behavior compared with UN, the same was not sufficient to promote cocaine reinstatement. In this study, we examined the long-term transcriptional changes that are induced by S-S compared to NS-S and linked the increased susceptibility of S-S mice to cocaine reinstatement. To this end, we performed genome-wide RNA sequencing analysis in the nucleus accumbens (NAC), which revealed that 89 transcripts were differentially expressed between S-S and NS-S mice. By Gene Ontology classification, these hits were enriched in genes that mediate cell proliferation, neuronal differentiation, and neuron/forebrain development. Eleven of these genes have been reported to be involved in substance use disorders, and the remaining genes are novel candidates in this area. We characterized 4 candidates with regard to their significant neurobiological relevance (ZIC1, ZIC2, FABP7, and PRDM12) and measured their expression in the NAC by immunohistochemistry. These findings provide insights into novel molecular mechanisms in NAC that might be associated with the risk of relapse in cocaine-dependent individuals. PMID:26706499

  20. Anti-cancer effects of p21WAF1/CIP1 transcriptional activation induced by dsRNAs in human hepatocellular carcinoma cell lines

    Institute of Scientific and Technical Information of China (English)

    Zhi-ming WU; Gang CHEN; Chun DAI; Ying HUANG; Cui-fang ZHENG; Qiong-zhu DONG; Guan WANG; Xiao-wen LI; Xiao-fei ZHANG; Bin LI

    2011-01-01

    Aim: To investigate the anti-cancer effects of p21WAF1/CIP1 transcriptional activation induced by dsRNAs in hepatocellular carcinoma (HCC) cell lines.Methods: HCC cell lines BEL7402, SMMC-7721, MHCC97L, MHCC97H, and MHCCLM3 were used. HCC ceils were treated with dsP21322 (50 nmol/L), dsControl (50 nmol/L), siP21 (50 nmol/L), or mock transfection. The expression of p21 was detected using quantitative PCR and Western blot. The effects of RNA activation on HCC cells were determined using cell viability assays, apoptosis analyses and clonogenic survival assays. Western blot was also conducted to detect the expression of Bcl-xL, survivin, cleaved caspase-3,cleaved caspase-9 and cleaved PARP.Results: At 72 to 120 h following the transfection, dsP21-322 markedly inhibited the viability of HCC cells and clone formation. At the same times, dsP21-322 caused a significant increase in HCC cell apoptosis, as demonstrated with cytometric analysis. The phenomena were correlated with decreased expression levels of the anti-apoptotic proteins Bcl-xL, surviving, and increased expression of cleaved caspase-3, cleaved caspase-9 and cleaved PARP.Conclusion: RNA-induced activation of p21 gene expression may have significant therapeutic potential for the treatment of hepatocellular carcinoma and other cancers.

  1. Immune-mediated mechanisms influencing the efficacy of anticancer therapies.

    Science.gov (United States)

    Coffelt, Seth B; de Visser, Karin E

    2015-04-01

    Conventional anticancer therapies, such as chemotherapy, radiotherapy, and targeted therapy, are designed to kill cancer cells. However, the efficacy of anticancer therapies is not only determined by their direct effects on cancer cells but also by off-target effects within the host immune system. Cytotoxic treatment regimens elicit several changes in immune-related parameters including the composition, phenotype, and function of immune cells. Here we discuss the impact of innate and adaptive immune cells on the success of anticancer therapy. In this context we examine the opportunities to exploit host immune responses to boost tumor clearing, and highlight the challenges facing the treatment of advanced metastatic disease. PMID:25857662

  2. In silico identification of anti-cancer compounds and plants from traditional Chinese medicine database

    Science.gov (United States)

    Dai, Shao-Xing; Li, Wen-Xing; Han, Fei-Fei; Guo, Yi-Cheng; Zheng, Jun-Juan; Liu, Jia-Qian; Wang, Qian; Gao, Yue-Dong; Li, Gong-Hua; Huang, Jing-Fei

    2016-05-01

    There is a constant demand to develop new, effective, and affordable anti-cancer drugs. The traditional Chinese medicine (TCM) is a valuable and alternative resource for identifying novel anti-cancer agents. In this study, we aim to identify the anti-cancer compounds and plants from the TCM database by using cheminformatics. We first predicted 5278 anti-cancer compounds from TCM database. The top 346 compounds were highly potent active in the 60 cell lines test. Similarity analysis revealed that 75% of the 5278 compounds are highly similar to the approved anti-cancer drugs. Based on the predicted anti-cancer compounds, we identified 57 anti-cancer plants by activity enrichment. The identified plants are widely distributed in 46 genera and 28 families, which broadens the scope of the anti-cancer drug screening. Finally, we constructed a network of predicted anti-cancer plants and approved drugs based on the above results. The network highlighted the supportive role of the predicted plant in the development of anti-cancer drug and suggested different molecular anti-cancer mechanisms of the plants. Our study suggests that the predicted compounds and plants from TCM database offer an attractive starting point and a broader scope to mine for potential anti-cancer agents.

  3. Regulating expressions of cyclin D1, pRb, and anti-cancer effects of deguelin on human Burkitt's lymphoma Daudi cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Hong-li LIU; Yan CHEN; Guo-hui CUI; Qiu-ling WU; Jing HE

    2005-01-01

    Aim: To investigate anticancer effects and molecular mechanism of deguelin on human Burkitt' s lymphoma Daudi cells in vitro and compare the cytotoxicities of deguelin on Daudi cells and human peripheral blood monocular cells (PBMC).Methods: The effects of deguelin on the growth of Daudi cells were studied by 3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium (MTT) assay.Apoptosis were dectected through Hoechst 33258 staining and Annexin V/PI double-labeled cytometry.The effect of deguelin on the cell cycle of Daudi cells were studied by a propidium iodide method.The expressions of cyclin D1 and pRb were checked by Western blot.Results: The proliferation of Daudi cells were decreased in deguelin-treated group with a 24-h IC50 value of 51.55 nmol/L.Deguelin induced Daudi cells apoptosis was in a time- and dose-dependent manner.G0/G1 phase increased and S phase decreased in Daudi cells treated with deguelin.With deguelin 0, 5, 10, 20, and 40 nmol/L treatment for 24 h, G0/G1 phase increased from 37.34% to 56.56%, whereas S phase decreased from 37.72% to 21.36%.PBMC was less sensitive to the cytotoxic effect of deguelin than Daudi cells.The expression of cyclin D 1 and pRb protein were decreased sharply in Daudi cells treated with deguelin.Conclusion: Deguelin is able to inhibit the proliferation of Daudi cells by regulating the cell cycle that arrested cells at G0/G1 phase and inducing the cell apoptosis.Moreover, deguelin selectively induced apoptosis of Daudi cells with low toxicity in PBMC.The antitumor effects of deguelin were related to downregulating the expression of cyclin D 1 and pRb protein.

  4. Reengineered tricyclic anti-cancer agents.

    Science.gov (United States)

    Kastrinsky, David B; Sangodkar, Jaya; Zaware, Nilesh; Izadmehr, Sudeh; Dhawan, Neil S; Narla, Goutham; Ohlmeyer, Michael

    2015-10-01

    The phenothiazine and dibenzazepine tricyclics are potent neurotropic drugs with a documented but underutilized anti-cancer side effect. Reengineering these agents (TFP, CPZ, CIP) by replacing the basic amine with a neutral polar functional group (e.g., RTC-1, RTC-2) abrogated their CNS effects as demonstrated by in vitro pharmacological assays and in vivo behavioral models. Further optimization generated several phenothiazines and dibenzazepines with improved anti-cancer potency, exemplified by RTC-5. This new lead demonstrated efficacy against a xenograft model of an EGFR driven cancer without the neurotropic effects exhibited by the parent molecules. Its effects were attributed to concomitant negative regulation of PI3K-AKT and RAS-ERK signaling. PMID:26372073

  5. Quantitative Analysis of the Relative Transcript Levels of ABC Transporter Atr Genes in Aspergillus nidulans by Real-Time Reverse Transcription-PCR Assay

    Science.gov (United States)

    Pizeta Semighini, Camile; Marins, Mozart; Goldman, Maria Helena S.; Goldman, Gustavo Henrique

    2002-01-01

    The development of assays for quantitative analysis of the relative transcript levels of ABC transporter genes by real-time reverse transcription-PCR (RT-PCR) might provide important information about multidrug resistance in filamentous fungi. Here, we evaluate the potential of real-time RT-PCR to quantify the relative transcript levels of ABC transporter Atr genes from Aspergillus nidulans. The AtrA to AtrD genes showed different and higher levels in the presence of structurally unrelated drugs, such as camptothecin, imazalil, itraconazole, hygromycin, and 4-nitroquinoline oxide. We also verified the relative transcript levels of the Atr genes in the A. nidulans imazalil-resistant mutants. These genes displayed a very complex pattern in different ima genetic backgrounds. The imaB mutant has higher basal transcript levels of AtrB and -D than those of the wild-type strain. The levels of these two genes are comparable when the imaB mutant is grown in the presence and absence of imazalil. The imaC, -D, and -H mutants have higher basal levels of AtrA than that of the wild type. The same behavior is observed for the relative transcript levels of AtrB in the imaG mutant background. PMID:11872487

  6. Studies of the effect on the cell cycle and of the radiosensitization of a novel anti-cancer agent TZT-1027

    International Nuclear Information System (INIS)

    The anticancer agent TZT-1027, an analog of dolastatin 10 originated from a marine organism, is an anti-microtubule agent and the present studies were performed to elucidate its activities in the title. Cell cycle analysis was done in mouse breast carcinoma tsFT210 cell line by flow-cytometry, which revealed that TZT-1027 specifically acted at G2/M, the stage most sensitive to radiation. Human non-small cell lung cancer H460 cell line was used for clonogenic assay: the dose enhancement factor at survival 0.1, estimated by the survival curve of cells irradiated by 60Co gamma ray at 0-6 Gy with or without TZT-1027, was found to be 1.2, which revealed the enhancement of radiosenstivity. In addition, their radiation-induced apoptosis was found to be also enhanced by the agent. When nude-mice transplanted with H460 cells were treated with TZT-1027 and 60Co gamma ray at 10 Gy, radiosensitization and apoptosis enhancement by the agent were also clear in vivo. Thus, TZT-1027 enhances the anti-tumor effect of radiation and this radiosensitizing mechanism involves the apoptotic process at least partly, both of which are conceivably the basis of future clinical trial of the agent. (T.I.)

  7. Medicinal Plants: Their Use in Anticancer Treatment

    OpenAIRE

    Greenwell, M.; Rahman, P.K.S.M.

    2015-01-01

    Globally cancer is a disease which severely effects the human population. There is a constant demand for new therapies to treat and prevent this life-threatening disease. Scientific and research interest is drawing its attention towards naturally-derived compounds as they are considered to have less toxic side effects compared to current treatments such as chemotherapy. The Plant Kingdom produces naturally occurring secondary metabolites which are being investigated for their anticancer activ...

  8. Specific internalization and synergistic anticancer effect of docetaxel-encapsulated chitosan-modified polymeric nanocarriers: a novel approach in cancer chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Asthana, Shalini; Gupta, Pramod K. [CSIR-Central Drug Research Institute, Pharmaceutics Division (India); Konwar, Rituraj [CSIR-Central Drug Research Institute, Endocrinology Division (India); Chourasia, Manish K., E-mail: manish_chourasia@cdri.res.in [CSIR-Central Drug Research Institute, Pharmaceutics Division (India)

    2013-09-15

    Nanocarriers can be surface engineered to increase endocytosis for applications in delivery of chemotherapeutics. This study investigated the chitosan (CS)-mediated effects on the anticancer efficacy and uptake of docetaxel-loaded nanometric particles (<250 nm) by MCF-7 tumor cells. Herein, negatively charged poly lactic-co-glycolic acid (PLGA) nanoparticles (-18.4 {+-} 2.57 mV, 162 {+-} 6.34 nm), poorly endocytosed by the MCF-7 cells, were subjected to surface modification with CS. It demonstrated significant increase (>5-fold) in intracellular uptake as well as antitumor efficacy of modified nanoparticles (NPs) that explicate the possibility of saccharide marker-mediated tumor targeting along with synergism via proapoptotic effect of CS. Additionally, high positivity of optimized tailored nanocarrier (+23.3 {+-} 2.02 mV, 242.8 {+-} 9.42 nm) may have accounted for the increased adsorption-mediated endocytosis, preferably toward tumor cells with negative potential. Developed drug carrier system showed high stability in human blood which is in compliance with mucoadhesive property of CS. Transmission electron microscopy technique was applied to observe shape and morphological features of NPs. Furthermore, in vivo tissue toxicity study revealed safe use of drug at 20 mg/kg dose in nanoparticulate form. Moreover, the enhanced in vitro uptake of these NPs and their cytotoxicity against the tumor cells along with synergistic effect of CS clearly suggest that CS-modified carrier system is a promising candidate for preclinical studies to achieve wider anti-tumor therapeutic window and lower side effects.

  9. Chemical and preclinical studies on Hedyotis diffusa with anticancer potential.

    Science.gov (United States)

    Niu, Yu; Meng, Qiu-Xia

    2013-01-01

    This paper presents the chemical and preclinical anticancer research on Hedyotis diffusa Willd. in detail, one of the most renowned herbs often prescribed in the polyherbal formulas for cancer treatment in traditional Chinese medicine. Anthraquinones, flavonoids, and terpenoids constitute the majority of the 69 compounds that have been isolated and identified from H. diffusa. The anticancer effects of the methanolic, ethanolic, and aqueous extracts in various preclinical cancer models have been described. This review also summarized the anticancer activity of constituents of the herb and the mechanisms of action. All the studies suggest that H. diffusa has enormous potential in the therapy of cancer and warrants further chemical and pharmacological investigation. PMID:23600735

  10. Transcript levels of ten caste-related genes in adult diploid males of Melipona quadrifasciata (Hymenoptera, Apidae: a comparison with haploid males, queens and workers

    Directory of Open Access Journals (Sweden)

    Andreia A. Borges

    2011-01-01

    Full Text Available In Hymenoptera, homozygosity at the sex locus results in the production of diploid males. In social species, these pose a double burden by having low fitness and drawing resources normally spent for increasing the work force of a colony. Yet, diploid males are of academic interest as they can elucidate effects of ploidy (normal males are haploid, whereas the female castes, the queens and workers, are diploid on morphology and life history. Herein we investigated expression levels of ten caste-related genes in the stingless bee Melipona quadrifasciata, comparing newly emerged and 5-day-old diploid males with haploid males, queens and workers. In diploid males, transcript levels for dunce and paramyosin were increased during the first five days of adult life, while those for diacylglycerol kinase and the transcriptional co-repressor groucho diminished. Two general trends were apparent, (i gene expression patterns in diploid males were overall more similar to haploid ones and workers than to queens, and (ii in queens and workers, more genes were up-regulated after emergence until day five, whereas in diploid and especially so in haploid males more genes were down-regulated. This difference between the sexes may be related to longevity, which is much longer in females than in males.

  11. Toxicities of anticancer drugs and its management

    Directory of Open Access Journals (Sweden)

    Ambili Remesh

    2012-02-01

    Full Text Available One of the characteristics that distinguish anticancer agents from other drugs is the frequency and severity of side effects at therapeutic doses. Most cytotoxic drugs target rapidly multiplying cells and the putative targets are the nucleic acids and their precursors, which are rapidly synthesised during cell division. Many solid tumours have a lower growth fraction than the normal bone marrow, gastro intestinal lining, reticuloendothelial system and gonads. Drugs affect these tissues in a dose dependant manner and there is individual susceptibility also. So toxicities are more frequently associated with these tissues. The side effects may be acute or chronic, self-limited, permanent, mild or potentially life threatening. Management of these side effects is of utmost importance because they affect the treatment, tolerability and overall quality of life. This paper gives an overview of different toxicities of anticancer drugs and its management. [Int J Basic Clin Pharmacol 2012; 1(1.000: 2-12

  12. Effects of a Shuangling Fuzheng anticancer preparation on the proliferation of SGC-7901 cells and immune function in a cyclophosphamide-treated murine model

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To study the inhibitory effects of a Shuangling Fuzheng anticancer preparation (SFAP) on the human gastric cancer cell line SGC-7901 in vitro as well as its immune-modulated effects in a cyclophosphamide-treated murine model.METHODS: MTT experiments and immunocytochemistry ABC experiments were performed for detecting the proliferation of SGC-7901 cells in vitro and protein expression of c-myc. The staphylococcal protein A (SPA) rosette test was utilized for measuring the ratio of T-lymphocyte subsets from peripheral blood in a cyclophosphamide-treated murine model. Enzymelinked immunosorbant assay (ELISA) was performed for measuring the levels of serum sIL-2R in treated mice, while immunoturbidimetry was used for measuring the levels of immunoglobulins (Ig).RESULTS: SFAP (40-640 mg/L, 48 h) inhibited the proliferation of SGC-7901 cells, and a positive correlation was noted between inhibitory effects and dosage. At a dosage of 160-320 mg/L in cultured cells, the expression of c-myc was decreased. SFAP (50-200 mg/kg) increased the percentage of CD3+ and CD4+ T-lymphocytes, the ratio of CD4/CD8, and the contents of Ig such as IgM,IgG or IgA, but decreased the levels of serum sIL-2R in peripheral blood from cyclophosphamide-treated mice.CONCLUSION: SFAP can inhibit the proliferation of SGC-7901 cells via the c-myc gene. In addition, SFAP can modulat the cellular and humoral immunity in cyclophosphamide-induced immunosuppressed mice.

  13. Anticancer effects of 15d-prostaglandin-J2 in wild-type and doxorubicin-resistant ovarian cancer cells: novel actions on SIRT1 and HDAC.

    Directory of Open Access Journals (Sweden)

    Edwin de Jong

    Full Text Available 15-Deoxy-delta-12,14-prostaglandin-J(2 (15d-PGJ(2, an arachidonic metabolite and a natural PPARγ agonist, is known to induce apoptosis in tumor cells. In this study, we investigated new therapeutic potentials of 15d-PGJ(2 by determining its anticancer effects in wild-type and doxorubicin-resistant ovarian carcinoma cells. Despite high expression of resistance-inducing genes like MDR1, Bcl2 and Bcl-xl, 15d-PGJ(2 strongly induced apoptosis in doxorubicin-resistant (A2780/AD cells similar to the wild-type (A2780. This was found to be related to caspase-3/7- and NF-κB pathways but not to its PPARγ agonistic activity. 15d-PGJ(2 also was able to reduce the doxorubicin resistance of A2780/AD cells at low doses as confirmed by the inhibition of gene expression of MDR1 (p-glycoprotein and SIRT1 (a drug senescence gene. We also investigated effects of 15d-PGJ(2 on cell migration and transformation using a wound-healing assay and morphological analyses, respectively. We found that 15d-PGJ(2 inhibited migration most likely due to NF-κB inhibition and induced transformation of the round-shape A2780/AD cells into elongated epithelial cells due to HDAC1 inhibition. Using a 15d-PGJ(2 analog, we found the mechanism of action of these new activities of 15d-PGJ(2 on SIRT1 and HDAC1 gene expressions and enzyme activities. In conclusion, the present study demonstrates that 15d-PGJ(2 has a high therapeutic potential to kill drug-resistant tumor cells and, the newly described inhibitory effects of this cyclo-oxygenase product on SIRT1 and HDAC will provide new opportunities for cancer therapeutics.

  14. 含黄酮类中药的抗癌抗肿瘤作用研究概况%The General Research on Effects of Flavonoids Ingredients of Chinese Herbs on Anti-cancer

    Institute of Scientific and Technical Information of China (English)

    王博

    2012-01-01

    黄酮类化合物是自然界中广泛存在的一大类化合物,具有多种多样的生物学活性,其抗癌抗肿瘤作用是目前的研究热点,它在中草药中分布,引来国内外学者对中草药中黄酮类成分的研究兴趣,发现其抗癌抗肿瘤作用与抗氧化、抗自由基、抑制癌细胞生长、抗致癌因子、调节免等作用相关.中草药中白花蛇舌草、陈皮、黄芩、夏枯草、半枝莲等含有较高的黄酮类成分,本文将对中草药中黄酮类成分的抗癌抗肿瘤作用进介绍.%Flavonoids is widespread compounds with various biological activities, its anti-cancer effects are the research hot-spot recently. It also has been greatly impressed by considerable domestic and foreign scientists due to the bioactivities of Flavonoids ingredients of Chinese herbs on anti-cancer. Its anti-cancer effect relates to antioxidation, inhibiting proliferation, anti-cancerigenic factor, mediated immune. Flavonoids distribute in many Chinese herbs, such as Hedyotis diffusa, Citrus, Scutellaria, Common Selfheal Fruit-Spike, Sculellaria barbata. This article introduces the effects of Flavonoids ingredients of Chinese herbs on anti-cancer.

  15. Dimethyl sulfoxide inactivates the anticancer effect of cisplatin against human myelogenous leukemia cell lines in in vitro assays

    OpenAIRE

    Rahul Raghavan; Sanith Cheriyamundath; Joseph Madassery

    2015-01-01

    Objectives: To investigate the effect of DMSO on cisplatin induced cytotoxicity (invitro) against K562 (Human mylogenous leukemia) cell line and to study the cisplatin-DMSO adduct formation using UV-spectrophotometer. Materials and methods: Effect of DMSO on the cytotoxicity of cisplatin was studied in K562 (Chronic mylogenous leukemia) cell line by MTT assay. Cisplatin-DMSO adduct formation was studied by continuously monitoring the increase in absorption peaks for 30 minutes using UV-s...

  16. Quantitative Analysis of the Relative Transcript Levels of ABC Transporter Atr Genes in Aspergillus nidulans by Real-Time Reverse Transcription-PCR Assay

    OpenAIRE

    Pizeta Semighini, Camile; Marins, Mozart; Goldman, Maria Helena S.; Goldman, Gustavo Henrique

    2002-01-01

    The development of assays for quantitative analysis of the relative transcript levels of ABC transporter genes by real-time reverse transcription-PCR (RT-PCR) might provide important information about multidrug resistance in filamentous fungi. Here, we evaluate the potential of real-time RT-PCR to quantify the relative transcript levels of ABC transporter Atr genes from Aspergillus nidulans. The AtrA to AtrD genes showed different and higher levels in the presence of structurally unrelated dr...

  17. Anti-cancer effect of bee venom toxin and melittin in ovarian cancer cells through induction of death receptors and inhibition of JAK2/STAT3 pathway

    Energy Technology Data Exchange (ETDEWEB)

    Jo, Miran; Park, Mi Hee; Kollipara, Pushpa Saranya [College of Pharmacy and Medical Research Center, Chungbuk National University, 48, Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk, 361-763 (Korea, Republic of); An, Byeong Jun; Song, Ho Sueb [College of Oriental Medicine, Kyungwon University, San 65, Bokjeong-dong, Sujeong-gu, Seongnam, Gyeonggii 461-701 (Korea, Republic of); Han, Sang Bae [College of Pharmacy and Medical Research Center, Chungbuk National University, 48, Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk, 361-763 (Korea, Republic of); Kim, Jang Heub [Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, 505, Banpo-dong, Seocho-gu, Seoul 137-040 (Korea, Republic of); Song, Min Jong, E-mail: bitsugar@catholic.ac.kr [Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, 505, Banpo-dong, Seocho-gu, Seoul 137-040 (Korea, Republic of); Hong, Jin Tae, E-mail: jinthong@chungbuk.ac.kr [College of Pharmacy and Medical Research Center, Chungbuk National University, 48, Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk, 361-763 (Korea, Republic of)

    2012-01-01

    We investigated whether bee venom and melittin, a major component of bee venom, inhibit cell growth through enhancement of death receptor expressions in the human ovarian cancer cells, SKOV3 and PA-1. Bee venom (1–5 μg/ml) and melittin (0.5–2 μg/ml) inhibited the growth of SKOV3 and PA-1 ovarian cancer cells by the induction of apoptotic cell death in a dose dependent manner. Consistent with apoptotic cell death, expression of death receptor (DR) 3 and DR6 was increased in both cancer cells, but expression of DR4 was increased only in PA-1 cells. Expression of DR downstream pro-apoptotic proteins including caspase-3, 8, and Bax was concomitantly increased, but the phosphorylation of JAK2 and STAT3 and the expression of Bcl-2 were inhibited by treatment with bee venom and melittin in SKOV3 and PA-1 cells. Expression of cleaved caspase-3 was increased in SKOV3, but cleaved caspase-8 was increased in PA-1 cells. Moreover, deletion of DR3, DR4, and DR6 by small interfering RNA significantly reversed bee venom and melittin-induced cell growth inhibitory effect as well as down regulation of STAT3 by bee venom and melittin in SKOV3 and PA-1 ovarian cancer cell. These results suggest that bee venom and melittin induce apoptotic cell death in ovarian cancer cells through enhancement of DR3, DR4, and DR6 expression and inhibition of STAT3 pathway. -- Highlights: ► Some studies have showed that bee venom and/or melittin have anti-cancer effects. ► We found that bee venom and melittin inhibited cell growth in ovarian cancer cells. ► Bee venom and melittin induce apoptosis in SKOV3 and PA-1.

  18. AMPK-mediated up-regulation of mTORC2 and MCL-1 compromises the anti-cancer effects of aspirin

    Science.gov (United States)

    Hua, Hui; Yin, Yancun; Wang, Jiao; Luo, Ting; Jiang, Yangfu

    2016-01-01

    AMP-activated protein kinase (AMPK) is an important energy sensor that may inhibit cell proliferation or promote cell survival during stresses. Besides cyclooxygenase, AMPK is another target of the nonsteroid anti-inflammatory agent aspirin. Preclinical and clinical investigations demonstrate that aspirin can inhibit several types of cancer such as colorectal adenomas and hepatocellular carcinoma (HCC). However, little is known about the cellular response to aspirin that may lead to aspirin resistance. Here, we show that aspirin induces the expression of MCL-1 in HepG2 and SW480 cells through AMPK-mTOR-Akt/ERK axis. Treatment of HepG2 and SW480 cells with aspirin leads to increased MCL-1 expression, Akt and ERK1/2 phosphorylation. Inhibition of Akt/MEK abrogates the induction of MCL-1 by aspirin. Aspirin activates AMPK, which in turn up-regulates mTORC2 activity, Akt, ERK1/2 phosphorylation and MCL-1 expression. MCL-1 knockdown sensitizes cancer cells to aspirin-induced apoptosis. Combination of aspirin and AMPK, Akt or MEK inhibitor results in more significant inhibition of cell proliferation and induction of apoptosis than single agent. Moreover, sorafenib blocks aspirin-induced MCL-1 up-regulation. Combination of aspirin and sorafenib leads to much more cell death and less cell proliferation than each drug alone. Treatment of HCC and colon cancer xenografts with both aspirin and sorafenib results in more significant tumor suppression than single agent. These data demonstrate that AMPK-mediated up-regulation of mTORC2 and MCL-1 may compromise the anticancer effects of aspirin. Combination of aspirin and sorafenib may be an effective regimen to treat HCC and colon cancer. PMID:26918349

  19. Anti-cancer effect of metformin by suppressing signaling pathway of HER2 and HER3 in tamoxifen-resistant breast cancer cells.

    Science.gov (United States)

    Kim, Jinkyoung; Lee, Jiyun; Kim, Chungyeul; Choi, Jinhyuk; Kim, Aeree

    2016-05-01

    Development of new therapeutic strategies is becoming increasingly important to overcome tamoxifen resistance. Recently, much interest has been focused on anti-tumor effects of metformin commonly used to treat type II diabetes. Increased protein expression and signaling of epidermal growth factor receptor (EGFR) family is a possible mechanism involved in tamoxifen resistance. Since HER2/HER3 heterodimers are able to induce strong downstream signaling and activate various biological responses such as cellular proliferation and growth, we investigated the anti-cancer effect of metformin by inhibition of signaling pathway via downregulation of HER2 and HER3 using tamoxifen-resistant MCF-7 (TR MCF-7) cells. Compared to MCF-7 cells, TR MCF-7 cells showed increased expression of EGFR, HER2, and HER3, and metformin inhibited the expression of these proteins in a dose- and time-dependent manner. Metformin inhibited activation of HER2 (Tyr1248)/HER3 (Tyr1289)/Akt (Ser473) as well as cell proliferation and colony formation by estrogenic promotion in MCF-7 and TR MCF-7 cells. Known as a HER3 ligand, heregulin (HRG)-β1-induced phosphorylation of HER2, HER3 and Akt, and protein interaction of HER2/HER3 and colony formation were inhibited by metformin in both cells. Consistent with the results in the two cell lines, we identified that metformin inhibited HER2/HER3/Akt signaling axis activated by HRG-β1 using the HER2 and HER3-overexpressing breast cancer cell line SK-BR-3. Lastly, lapatinib-induced HER3 upregulation was significantly inhibited by treatment of metformin in HER3 siRNA-transfected TR MCF-7 cells. These data suggest that metformin might overcome tamoxifen resistance through the inhibition of expression and signaling of receptor tyrosine kinase HER2 and HER3. PMID:26581908

  20. Effect of anticancer drugs on breast cancer cells sensitive and resistant to doxorubicin: expression of mRNAs of TGF-β and its receptors

    Directory of Open Access Journals (Sweden)

    Chorna I. V.

    2014-01-01

    Full Text Available Aim. Comparative study of the effect of chemotherapeutic drugs (doxorubicin, methotrexate and cisplatin and TGF-β on the human breast carcinoma MCF-7 cells, sensitive (wt and resistant (DOX/R to the doxorubicin action. Methods. Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR was used for the estimation of expression of mRNAs coding for the TGF-β isoforms (TGF-β1 and TGF-β2 and the TGF-β type I and II receptors (TRI and TRII. Trypan blue exclusion method was used for measuring cell number and cell viability. Results. The MCF-7(DOX/R cells were more refractory to the TGF1-dependent growth inhibition than the MCF-7(wt cells. The level of mRNAs coding for TGF and its receptors was higher in the untreated MCF-7 (DOX/R cells comparing to the MCF-7(wt cells. The expression of mRNA coding for TRII was decreased in both cell lines treated with doxorubicin, methotrexate and cisplatin, while the down-regulation of mRNA coding for TRI was revealed only in the MCF-7(DOX/R cells upon the treatment with doxorubicin and methotrexate. Conclusions. The differential effects of studied anticancer drugs and TGF-β on the doxorubicin-sensitive and -resistant cells have been demonstrated. The elucidation of the molecular mechanisms of escape of the MCF-7 (DOX/R cells from the growth inhibition by TGF-β requires further investigation.

  1. Thymoquinone overcomes chemoresistance and enhances the anticancer effects of bortezomib through abrogation of NF-κB regulated gene products in multiple myeloma xenograft mouse model.

    Science.gov (United States)

    Siveen, Kodappully Sivaraman; Mustafa, Nurulhuda; Li, Feng; Kannaiyan, Radhamani; Ahn, Kwang Seok; Kumar, Alan Prem; Chng, Wee-Joo; Sethi, Gautam

    2014-02-15

    Multiple myeloma (MM) is a B cell malignancy characterized by clonal proliferation of plasma cells in the bone marrow. With the advent of novel targeted agents, the median survival rate has increased to 5 -7 years. However, majority of patients with myeloma suffer relapse or develop chemoresistance to existing therapeutic agents. Thus, there is a need to develop novel alternative therapies for the treatment of MM. Thus in the present study, we investigated whether thymoquinone (TQ), a bioactive constituent of black seed oil, could suppress the proliferation and induce chemosensitization in human myeloma cells and xenograft mouse model. Our results show that TQ inhibited the proliferation of MM cells irrespective of their sensitivity to doxorubicin, melphalan or bortezomib. Interestingly, TQ treatment also resulted in a significant inhibition in the proliferation of CD138+ cells isolated from MM patient samples in a concentration dependent manner. TQ also potentiated the apoptotic effects of bortezomib in various MM cell lines through the activation of caspase-3, resulting in the cleavage of PARP. TQ treatment also inhibited chemotaxis and invasion induced by CXCL12 in MM cells. Furthermore, in a xenograft mouse model, TQ potentiated the antitumor effects of bortezomib (p<0.05, vehicle versus bortezomib + TQ; p<0.05, bortezomib versus bortezomib + TQ), and this correlated with modulation of various markers for survival and angiogenesis, such as Ki-67, vascular endothelial growth factor (VEGF), Bcl-2 and p65 expression. Overall, our results demonstrate that TQ can enhance the anticancer activity of bortezomib in vitro and in vivo and may have a substantial potential in the treatment of MM. PMID:24504138

  2. Anti-cancer effect of bee venom toxin and melittin in ovarian cancer cells through induction of death receptors and inhibition of JAK2/STAT3 pathway

    International Nuclear Information System (INIS)

    We investigated whether bee venom and melittin, a major component of bee venom, inhibit cell growth through enhancement of death receptor expressions in the human ovarian cancer cells, SKOV3 and PA-1. Bee venom (1–5 μg/ml) and melittin (0.5–2 μg/ml) inhibited the growth of SKOV3 and PA-1 ovarian cancer cells by the induction of apoptotic cell death in a dose dependent manner. Consistent with apoptotic cell death, expression of death receptor (DR) 3 and DR6 was increased in both cancer cells, but expression of DR4 was increased only in PA-1 cells. Expression of DR downstream pro-apoptotic proteins including caspase-3, 8, and Bax was concomitantly increased, but the phosphorylation of JAK2 and STAT3 and the expression of Bcl-2 were inhibited by treatment with bee venom and melittin in SKOV3 and PA-1 cells. Expression of cleaved caspase-3 was increased in SKOV3, but cleaved caspase-8 was increased in PA-1 cells. Moreover, deletion of DR3, DR4, and DR6 by small interfering RNA significantly reversed bee venom and melittin-induced cell growth inhibitory effect as well as down regulation of STAT3 by bee venom and melittin in SKOV3 and PA-1 ovarian cancer cell. These results suggest that bee venom and melittin induce apoptotic cell death in ovarian cancer cells through enhancement of DR3, DR4, and DR6 expression and inhibition of STAT3 pathway. -- Highlights: ► Some studies have showed that bee venom and/or melittin have anti-cancer effects. ► We found that bee venom and melittin inhibited cell growth in ovarian cancer cells. ► Bee venom and melittin induce apoptosis in SKOV3 and PA-1.

  3. siRNA inhibition of telomerase enhances the anti-cancer effect of doxorubicin in breast cancer cells

    International Nuclear Information System (INIS)

    Doxorubicin is an effective breast cancer drug but is hampered by a severe, dose-dependent toxicity. Concomitant administration of doxorubicin and another cancer drug may be able to sensitize tumor cells to the cytotoxicity of doxorubicin and lowers the therapeutic dosage. In this study, we examined the combined effect of low-dose doxorubicin and siRNA inhibition of telomerase on breast cancer cells. We found that when used individually, both treatments were rapid and potent apoptosis inducers; and when the two treatments were combined, we observed an enhanced and sustained apoptosis induction in breast cancer cells. siRNA targeting the mRNA of the protein component of telomerase, the telomerase reverse transcriptase (hTERT), was transfected into two breast cancer cell lines. The siRNA inhibition was confirmed by RT-PCR and western blot on hTERT mRNA and protein levels, respectively, and by measuring the activity level of telomerase using the TRAP assay. The effect of the hTERT siRNA on the tumorigenicity of the breast cancer cells was also studied in vivo by injection of the siRNA-transfected breast cancer cells into nude mice. The effects on cell viability, apoptosis and senescence of cells treated with hTERT siRNA, doxorubicin, and the combined treatment of doxorubicin and hTERT siRNA, were examined in vitro by MTT assay, FACS and SA-β-galactosidase staining. The hTERT siRNA effectively knocked down the mRNA and protein levels of hTERT, and reduced the telomerase activity to 30% of the untreated control. In vivo, the tumors induced by the hTERT siRNA-transfected cells were of reduced sizes, indicating that the hTERT siRNA also reduced the tumorigenic potential of the breast cancer cells. The siRNA treatment reduced cell viability by 50% in breast cancer cells within two days after transfection, while 0.5 μM doxorubicin treatment had a comparable effect but with a slower kinetics. The combination of hTERT siRNA and 0.5 μM doxorubicin killed twice as many

  4. Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance.

    Science.gov (United States)

    Pietrocola, Federico; Pol, Jonathan; Vacchelli, Erika; Rao, Shuan; Enot, David P; Baracco, Elisa E; Levesque, Sarah; Castoldi, Francesca; Jacquelot, Nicolas; Yamazaki, Takahiro; Senovilla, Laura; Marino, Guillermo; Aranda, Fernando; Durand, Sylvère; Sica, Valentina; Chery, Alexis; Lachkar, Sylvie; Sigl, Verena; Bloy, Norma; Buque, Aitziber; Falzoni, Simonetta; Ryffel, Bernhard; Apetoh, Lionel; Di Virgilio, Francesco; Madeo, Frank; Maiuri, Maria Chiara; Zitvogel, Laurence; Levine, Beth; Penninger, Josef M; Kroemer, Guido

    2016-07-11

    Caloric restriction mimetics (CRMs) mimic the biochemical effects of nutrient deprivation by reducing lysine acetylation of cellular proteins, thus triggering autophagy. Treatment with the CRM hydroxycitrate, an inhibitor of ATP citrate lyase, induced the depletion of regulatory T cells (which dampen anticancer immunity) from autophagy-competent, but not autophagy-deficient, mutant KRAS-induced lung cancers in mice, thereby improving anticancer immunosurveillance and reducing tumor mass. Short-term fasting or treatment with several chemically unrelated autophagy-inducing CRMs, including hydroxycitrate and spermidine, improved the inhibition of tumor growth by chemotherapy in vivo. This effect was only observed for autophagy-competent tumors, depended on the presence of T lymphocytes, and was accompanied by the depletion of regulatory T cells from the tumor bed. PMID:27411589

  5. Isocorydine Derivatives and Their Anticancer Activities

    Directory of Open Access Journals (Sweden)

    Mei Zhong

    2014-08-01

    Full Text Available In order to improve the anticancer activity of isocorydine (ICD, ten isocorydine derivatives were prepared through chemical structure modifications, and their in vitro and in vivo activities were experimentally investigated. 8-Amino-isocorydine (8 and 6a,7-dihydrogen-isocorydione (10 could inhibit the growth of human lung (A549, gastric (SGC7901 and liver (HepG2 cancer cell lines in vitro. Isocorydione (2 could inhibit the tumor growth of murine sarcoma S180-bearing mice, and 8-acetamino-isocorydine (11, a pro-drug of 8-amino-isocorydine (8, which is instable in water solution at room temperature, had a good inhibitory effect on murine hepatoma H22-induced tumors. The results suggested that the isocorydine structural modifications at C-8 could significantly improve the biological activity of this alkaloid, indicating its suitability as a lead compound in the development of an effective anticancer agent.

  6. SETDB1 mediated FosB expression increases the cell proliferation rate during anticancer drug therapy

    Science.gov (United States)

    Na, Han-Heom; Noh, Hee-Jung; Cheong, Hyang-Min; Kang, Yoonsung; Kim, Keun-Cheol

    2016-01-01

    The efficacy of anticancer drugs depends on a variety of signaling pathways, which can be positively or negatively regulated. In this study, we show that SETDB1 HMTase is down-regulated at the transcriptional level by several anticancer drugs, due to its inherent instability. Using RNA sequence analysis, we identified FosB as being regulated by SETDB1 during anticancer drug therapy. FosB expression was increased by treatment with doxorubicin, taxol and siSETDB1. Moreover, FosB was associated with an increased rate of proliferation. Combinatory transfection of siFosB and siSETDB1 was slightly increased compared to transfection of siFosB. Furthermore, FosB was regulated by multiple kinase pathways. ChIP analysis showed that SETDB1 and H3K9me3 interact with a specific region of the FosB promoter. These results suggest that SETDB1-mediated FosB expression is a common molecular phenomenon, and might be a novel pathway responsible for the increase in cell proliferation that frequently occurs during anticancer drug therapy. [BMB Reports 2016; 49(4): 238-243] PMID:26949019

  7. Optimization of personalized therapies for anticancer treatment

    OpenAIRE

    Vazquez, Alexei

    2013-01-01

    Background As today, there are hundreds of targeted therapies for the treatment of cancer, many of which have companion biomarkers that are in use to inform treatment decisions. If we would consider this whole arsenal of targeted therapies as a treatment option for every patient, very soon we will reach a scenario where each patient is positive for several markers suggesting their treatment with several targeted therapies. Given the documented side effects of anticancer drugs, it is clear tha...

  8. Oral mucositis induced by anticancer treatments: physiopathology and treatments

    OpenAIRE

    Lionel, D'Hondt; Christophe, Lonchay; Marc, André; Jean-Luc, Canon

    2006-01-01

    Oral mucositis is a frequent and devastating side effect of anticancer treatments. It impairs the patient's quality of life and also can be life threatening because severe infections and delayed or incomplete anticancer treatments may result. This problem has been largely overlooked and underestimated in the past. However, recently studies have been performed to precisely identify the epidemiology, cost, consequences, physiopathology, and treatments of oral mucositis. Clinical guidelines have...

  9. Anti-cancer potential of South Asian plants

    OpenAIRE

    Rahman, Mohammad Mijanur; Khan, Md Asaduzzaman

    2013-01-01

    Phyto-chemicals are increasingly being used in the treatment of cancer because of their availability, potential anti-cancer activity with less adverse effects when compared with chemotherapy. The variation of climate and geography in South Asian countries provides a nursing environment for the growth of versatile plant species, that are repeatedly drawing attention of the scientific community. In this review, we have focused on the anti-cancer potential of thirty plants, which are commonly fo...

  10. Molecular mechanisms of cytotoxic side effects of platinum anti-cancer drugs – a molecular orbital study

    OpenAIRE

    Fong, Clifford,

    2015-01-01

    The side effects of Pt drugs have been examined by evaluating the literature on Pt chemistry, pharmacology, cellular transport, and clinical efficacy and correlating these studies with molecular orbital computations. It is concluded that Pt chemotherapeutical regimes are dominated by side reactions, particularly hydrolysis in blood serum and delivery efficiency. For example, it is shown that transplatin is therapeutically inactive because it hydrolyses faster in blood serum than ciplatin, so ...

  11. Molecular profiling of signalling proteins for effects induced by the anti-cancer compound GSAO with 400 antibodies

    International Nuclear Information System (INIS)

    GSAO (4-[N-[S-glutathionylacetyl]amino] phenylarsenoxide) is a hydrophilic derivative of the protein tyrosine phosphatase inhibitor phenylarsine oxide (PAO). It inhibits angiogenesis and tumour growth in mouse models and may be evaluated in a phase I clinical trial in the near future. Initial experiments have implicated GSAO in perturbing mitochondrial function. Other molecular effects of GSAO in human cells, for example on the phosphorylation of proteins, are still largely unknown. Peripheral white blood cells (PWBC) from healthy volunteers were isolated and used to profile effects of GSAO vs. a control compound, GSCA. Changes in site-specific phosphorylations, other protein modifications and expression levels of many signalling proteins were analysed using more than 400 different antibodies in Western blots. PWBC were initially cultured in low serum conditions, with the aim to reduce basal protein phosphorylation and to increase detection sensitivity. Under these conditions pleiotropic intracellular signalling protein changes were induced by GSAO. Subsequently, PWBC were cultured in 100% donor serum to reflect more closely in vivo conditions. This eliminated detectable GSAO effects on most, but not all signalling proteins analysed. Activation of the MAP kinase Erk2 was still observed and the paxillin homologue Hic-5 still displayed a major shift in protein mobility upon GSAO-treatment. A GSAO induced change in Hic-5 mobility was also found in endothelial cells, which are thought to be the primary target of GSAO in vivo. Serum conditions greatly influence the molecular activity profile of GSAO in vitro. Low serum culture, which is typically used in experiments analysing protein phosphorylation, is not suitable to study GSAO activity in cells. The signalling proteins affected by GSAO under high serum conditions are candidate surrogate markers for GSAO bioactivity in vivo and can be analysed in future clinical trials. GSAO effects on Hic-5 in endothelial cells may

  12. Anti-cancer potential of MAPK pathway inhibition in paragangliomas-effect of different statins on mouse pheochromocytoma cells.

    Directory of Open Access Journals (Sweden)

    Stephanie M J Fliedner

    Full Text Available To date, malignant pheochromocytomas and paragangliomas (PHEOs/PGLs cannot be effectively cured and thus novel treatment strategies are urgently needed. Lovastatin has been shown to effectively induce apoptosis in mouse PHEO cells (MPC and the more aggressive mouse tumor tissue-derived cells (MTT, which was accompanied by decreased phosphorylation of mitogen-activated kinase (MAPK pathway players. The MAPK pathway plays a role in numerous aggressive tumors and has been associated with a subgroup of PHEOs/PGLs, including K-RAS-, RET-, and NF1-mutated tumors. Our aim was to establish whether MAPK signaling may also play a role in aggressive, succinate dehydrogenase (SDH B mutation-derived PHEOs/PGLs. Expression profiling and western blot analysis indicated that specific aspects of MAPK-signaling are active in SDHB PHEOs/PGLs, suggesting that inhibition by statin treatment could be beneficial. Moreover, we aimed to assess whether the anti-proliferative effect of lovastatin on MPC and MTT differed from that exerted by fluvastatin, simvastatin, atorvastatin, pravastatin, or rosuvastatin. Simvastatin and fluvastatin decreased cell proliferation most effectively and the more aggressive MTT cells appeared more sensitive in this respect. Inhibition of MAPK1 and 3 phosphorylation following treatment with fluvastatin, simvastatin, and lovastatin was confirmed by western blot. Increased levels of CASP-3 and PARP cleavage confirmed induction of apoptosis following the treatment. At a concentration low enough not to affect cell proliferation, spontaneous migration of MPC and MTT was significantly inhibited within 24 hours of treatment. In conclusion, lipophilic statins may present a promising therapeutic option for treatment of aggressive human paragangliomas by inducing apoptosis and inhibiting tumor spread.

  13. Anti-Cancer Potential of MAPK Pathway Inhibition in Paragangliomas–Effect of Different Statins on Mouse Pheochromocytoma Cells

    Science.gov (United States)

    Lendvai, Nikoletta K.; Shankavaram, Uma; Nölting, Svenja; Wesley, Robert; Elkahloun, Abdel G.; Ungefroren, Hendrik; Oldoerp, Angela; Lampert, Gary; Lehnert, Hendrik; Timmers, Henri; Pacak, Karel

    2014-01-01

    To date, malignant pheochromocytomas and paragangliomas (PHEOs/PGLs) cannot be effectively cured and thus novel treatment strategies are urgently needed. Lovastatin has been shown to effectively induce apoptosis in mouse PHEO cells (MPC) and the more aggressive mouse tumor tissue-derived cells (MTT), which was accompanied by decreased phosphorylation of mitogen-activated kinase (MAPK) pathway players. The MAPK pathway plays a role in numerous aggressive tumors and has been associated with a subgroup of PHEOs/PGLs, including K-RAS-, RET-, and NF1-mutated tumors. Our aim was to establish whether MAPK signaling may also play a role in aggressive, succinate dehydrogenase (SDH) B mutation-derived PHEOs/PGLs. Expression profiling and western blot analysis indicated that specific aspects of MAPK-signaling are active in SDHB PHEOs/PGLs, suggesting that inhibition by statin treatment could be beneficial. Moreover, we aimed to assess whether the anti-proliferative effect of lovastatin on MPC and MTT differed from that exerted by fluvastatin, simvastatin, atorvastatin, pravastatin, or rosuvastatin. Simvastatin and fluvastatin decreased cell proliferation most effectively and the more aggressive MTT cells appeared more sensitive in this respect. Inhibition of MAPK1 and 3 phosphorylation following treatment with fluvastatin, simvastatin, and lovastatin was confirmed by western blot. Increased levels of CASP-3 and PARP cleavage confirmed induction of apoptosis following the treatment. At a concentration low enough not to affect cell proliferation, spontaneous migration of MPC and MTT was significantly inhibited within 24 hours of treatment. In conclusion, lipophilic statins may present a promising therapeutic option for treatment of aggressive human paragangliomas by inducing apoptosis and inhibiting tumor spread. PMID:24846270

  14. Anti-cancer potential of MAPK pathway inhibition in paragangliomas-effect of different statins on mouse pheochromocytoma cells.

    Science.gov (United States)

    Fliedner, Stephanie M J; Engel, Tobias; Lendvai, Nikoletta K; Shankavaram, Uma; Nölting, Svenja; Wesley, Robert; Elkahloun, Abdel G; Ungefroren, Hendrik; Oldoerp, Angela; Lampert, Gary; Lehnert, Hendrik; Timmers, Henri; Pacak, Karel

    2014-01-01

    To date, malignant pheochromocytomas and paragangliomas (PHEOs/PGLs) cannot be effectively cured and thus novel treatment strategies are urgently needed. Lovastatin has been shown to effectively induce apoptosis in mouse PHEO cells (MPC) and the more aggressive mouse tumor tissue-derived cells (MTT), which was accompanied by decreased phosphorylation of mitogen-activated kinase (MAPK) pathway players. The MAPK pathway plays a role in numerous aggressive tumors and has been associated with a subgroup of PHEOs/PGLs, including K-RAS-, RET-, and NF1-mutated tumors. Our aim was to establish whether MAPK signaling may also play a role in aggressive, succinate dehydrogenase (SDH) B mutation-derived PHEOs/PGLs. Expression profiling and western blot analysis indicated that specific aspects of MAPK-signaling are active in SDHB PHEOs/PGLs, suggesting that inhibition by statin treatment could be beneficial. Moreover, we aimed to assess whether the anti-proliferative effect of lovastatin on MPC and MTT differed from that exerted by fluvastatin, simvastatin, atorvastatin, pravastatin, or rosuvastatin. Simvastatin and fluvastatin decreased cell proliferation most effectively and the more aggressive MTT cells appeared more sensitive in this respect. Inhibition of MAPK1 and 3 phosphorylation following treatment with fluvastatin, simvastatin, and lovastatin was confirmed by western blot. Increased levels of CASP-3 and PARP cleavage confirmed induction of apoptosis following the treatment. At a concentration low enough not to affect cell proliferation, spontaneous migration of MPC and MTT was significantly inhibited within 24 hours of treatment. In conclusion, lipophilic statins may present a promising therapeutic option for treatment of aggressive human paragangliomas by inducing apoptosis and inhibiting tumor spread. PMID:24846270

  15. Molecular Basis of the Anti-Cancer Effects of Genistein Isoflavone in LNCaP Prostate Cancer Cells.

    OpenAIRE

    Hartmann J; Zoeller R; Esiobu N; Rathinavelu A; Kumi-Diaka J; Merchant K; Johnson M

    2011-01-01

    Background: Prostate cancer is the most common form of non-skin cancer within the United States and the second leading cause of cancer deaths. Survival rates for the advanced disease remain relatively low, and conventional treatments may be accompanied by significant side effects. As a result, current research is aimed at alternative or adjuvant treatments that will target components of the signal transduction, cell-cycle and apoptosis pathways, to induce cell death with little or no toxic si...

  16. Anti-cancer effect and gene modulation of ET-743 in human biliary tract carcinoma preclinical models

    OpenAIRE

    Peraldo-Neia, Caterina; Cavalloni, Giuliana; Soster, Marco; Gammaitoni, Loretta; Marchiò, Serena; Sassi, Francesco; Trusolino, Livio; Bertotti, Andrea; Medico, Enzo; Capussotti, Lorenzo; Aglietta, Massimo; Leone, Francesco

    2014-01-01

    Background Standard chemotherapy in unresectable biliary tract carcinoma (BTC) patients is based on gemcitabine combined with platinum derivatives. However, primary or acquired resistance is inevitable and no second-line chemotherapy is demonstrated to be effective. Thus, there is an urgent need to identify new alternative (chemo)therapy approaches. Methods We evaluated the mechanism of action of ET-743 in preclinical models of BTC. Six BTC cell lines (TFK-1, EGI-1, TGBC1, WITT, KMCH, HuH28),...

  17. Aminoflavone-loaded EGFR-targeted unimolecular micelle nanoparticles exhibit anti-cancer effects in triple negative breast cancer.

    Science.gov (United States)

    Brinkman, Ashley M; Chen, Guojun; Wang, Yidan; Hedman, Curtis J; Sherer, Nathan M; Havighurst, Thomas C; Gong, Shaoqin; Xu, Wei

    2016-09-01

    Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer for which there is no available targeted therapy. TNBC cases contribute disproportionately to breast cancer-related mortality, thus the need for novel and effective therapeutic methods is urgent. We have previously shown that a National Cancer Institute (NCI) investigational drug aminoflavone (AF) exhibits strong growth inhibitory effects in TNBC cells. However, in vivo pulmonary toxicity resulted in withdrawal or termination of several human clinical trials for AF. Herein we report the in vivo efficacy of a nanoformulation of AF that enhances the therapeutic index of AF in TNBC. We engineered a unique unimolecular micelle nanoparticle (NP) loaded with AF and conjugated with GE11, a 12 amino acid peptide targeting epidermal growth factor receptor (EGFR), since EGFR amplification is frequently observed in TNBC tumors. These unimolecular micelles possessed excellent stability and preferentially released drug payload at endosomal pH levels rather than blood pH levels. Use of the GE11 targeting peptide resulted in enhanced cellular uptake and strong growth inhibitory effects in TNBC cells. Further, AF-loaded, GE11-conjugated (targeted) unimolecular micelle NPs significantly inhibit orthotopic TNBC tumor growth in a xenograft model, compared to treatment with AF-loaded, GE11-lacking (non-targeted) unimolecular micelle NPs or free AF. Interestingly, the animals treated with AF-loaded, targeted NPs had the highest plasma and tumor level of AF among different treatment groups yet exhibited no increase in plasma aspartate aminotransferase (AST) activity level or observable tissue damage at the time of sacrifice. Together, these results highlight AF-loaded, EGFR-targeted unimolecular micelle NPs as an effective therapeutic option for EGFR-overexpressing TNBC. PMID:27267625

  18. D-Amino acid oxidase-induced oxidative stress, 3-bromopyruvate and citrate inhibit angiogenesis, exhibiting potent anticancer effects.

    Science.gov (United States)

    El Sayed, S M; El-Magd, R M Abou; Shishido, Y; Yorita, K; Chung, S P; Tran, D H; Sakai, T; Watanabe, H; Kagami, S; Fukui, K

    2012-10-01

    Angiogenesis is critical for cancer growth and metastasis. Steps of angiogenesis are energy consuming, while vascular endothelial cells are highly glycolytic. Glioblastoma multiforme (GBM) is a highly vascular tumor and this enhances its aggressiveness. D-amino acid oxidase (DAO) is a promising therapeutic protein that induces oxidative stress upon acting on its substrates. Oxidative stress-energy depletion (OSED) therapy was recently reported (El Sayed et al., Cancer Gene Ther, 19, 1-18, 2012). OSED combines DAO-induced oxidative stress with energy depletion caused by glycolytic inhibitors such as 3-bromopyruvate (3BP), a hexokinase II inhibitor that depleted ATP in cancer cells and induced production of hydrogen peroxide. 3BP disturbs the Warburg effect and antagonizes effects of lactate and pyruvate (El Sayed et al., J Bioenerg Biomembr, 44, 61-79, 2012). Citrate is a natural organic acid capable of inhibiting glycolysis by targeting phosphofructokinase. Here, we report that DAO, 3BP and citrate significantly inhibited angiogenesis, decreased the number of vascular branching points and shortened the length of vascular tubules. OSED delayed the growth of C6/DAO glioma cells. 3BP combined with citrate delayed the growth of C6 glioma cells and decreased significantly the number and size of C6 glioma colonies in soft agar. Human GBM cells (U373MG) were resistant to chemotherapy e.g. cisplatin and cytosine arabinoside, while 3BP was effective in decreasing the viability and disturbing the morphology of U373MG cells. PMID:22802136

  19. Oral delivery of anticancer drugs

    DEFF Research Database (Denmark)

    Thanki, Kaushik; Gangwal, Rahul P; Sangamwar, Abhay T;

    2013-01-01

    The present report focuses on the various aspects of oral delivery of anticancer drugs. The significance of oral delivery in cancer therapeutics has been highlighted which principally includes improvement in quality of life of patients and reduced health care costs. Subsequently, the challenges...... incurred in the oral delivery of anticancer agents have been especially emphasized. Sincere efforts have been made to compile the various physicochemical properties of anticancer drugs from either literature or predicted in silico via GastroPlus™. The later section of the paper reviews various emerging...... trends to tackle the challenges associated with oral delivery of anticancer drugs. These invariably include efflux transporter based-, functional excipient- and nanocarrier based-approaches. The role of drug nanocrystals and various others such as polymer based- and lipid based-nanocarriers in the...

  20. Searching in mother nature for anti-cancer activity: anti-proliferative and pro-apoptotic effect elicited by green barley on leukemia/lymphoma cells.

    Directory of Open Access Journals (Sweden)

    Elisa Robles-Escajeda

    Full Text Available Green barley extract (GB was investigated for possible anti-cancer activity by examining its anti-proliferative and pro-apoptotic properties on human leukemia/lymphoma cell lines. Our results indicate that GB exhibits selective anti-proliferative activity on a panel of leukemia/lymphoma cells in comparison to non-cancerous cells. Specifically, GB disrupted the cell-cycle progression within BJAB cells, as manifested by G2/M phase arrest and DNA fragmentation, and induced apoptosis, as evidenced by phosphatidylserine (PS translocation to the outer cytoplasmic membrane in two B-lineage leukemia/lymphoma cell lines. The pro-apoptotic effect of GB was found to be independent of mitochondrial depolarization, thus implicating extrinsic cell death pathways to exert its cytotoxicity. Indeed, GB elicited an increase of TNF-α production, caspase-8 and caspase-3 activation, and PARP-1 cleavage within pre-B acute lymphoblastic leukemia Nalm-6 cells. Moreover, caspase-8 and caspase-3 activation and PARP-1 cleavage were strongly inhibited/blocked by the addition of the specific caspase inhibitors Z-VAD-FMK and Ac-DEVD-CHO. Furthermore, intracellular signaling analyses determined that GB treatment enhanced constitutive activation of Lck and Src tyrosine kinases in Nalm-6 cells. Taken together, these findings indicate that GB induced preferential anti-proliferative and pro-apoptotic signals within B-lineage leukemia/lymphoma cells, as determined by the following biochemical hallmarks of apoptosis: PS externalization, enhanced release of TNF-α, caspase-8 and caspase-3 activation, PARP-1 cleavage and DNA fragmentation Our observations reveal that GB has potential as an anti-leukemia/lymphoma agent alone or in combination with standard cancer therapies and thus warrants further evaluation in vivo to support these findings.

  1. Molecular mechanism of anticancer effect of Sclerotium rolfsii lectin in HT29 cells involves differential expression of genes associated with multiple signaling pathways: A microarray analysis.

    Science.gov (United States)

    Barkeer, Srikanth; Guha, Nilanjan; Hothpet, Vishwanathreddy; Saligrama Adavigowda, Deepak; Hegde, Prajna; Padmanaban, Arunkumar; Yu, Lu-Gang; Swamy, Bale M; Inamdar, Shashikala R

    2015-12-01

    Sclerotium rolfsii lectin (SRL) is a lectin isolated from fungus S. rolfsii and has high binding specificity toward the oncofetal Thomsen-Friedenreich carbohydrate antigen (Galβ1-3GalNAc-α-O-Ser/Thr, T or TF), which is expressed in more than 90% of human cancers. Our previous studies have shown that binding of SRL to human colon, breast and ovarian cancer cells induces cell apoptosis in vitro and suppresses tumor growth in vivo. This study investigated the SRL-mediated cell signaling in human colon cancer HT29 cells by mRNA and miRNA microarrays. It was found that SRL treatment results in altered expression of several hundred molecules including mitogen-activated protein kinase (MAPK) and c-JUN-associated, apoptosis-associated and cell cycle and DNA replication-associated signaling molecules. Pathway analysis using GeneSpring 12.6.1 revealed that SRL treatment induces changes of MAPK and c-JUN-associated signaling pathways as early as 2 h while changes of cell cycle, DNA replication and apoptosis pathways were significantly affected only after 24 h. A significant change of cell miRNA expression was also observed after 12 h treatment of the cells with SRL. These changes were further validated by quantitative real time polymerase chain reaction and immunoblotting. This study thus suggests that the presence of SRL affects multiple signaling pathways in cancer cells with early effects on cell proliferation pathways associated with MAPK and c-JUN, followed by miRNA-associated cell activity and apoptosis. This provides insight information into the molecular mechanism of the anticancer activity of this fungal lectin. PMID:26347523

  2. Anticancer effects of monocarbonyl analogs of curcumin: oxidative stress, nuclear translocation and modulation of AP-1 and NF-κB

    Directory of Open Access Journals (Sweden)

    Brian Adams

    2015-01-01

    Full Text Available Purpose: In order to elucidate anticancer effects of monocarbonyl analogs of curcumin (MACs, we have undertaken the present study to obtain information regarding drug targets by using a microarray approach, and to study the cellular localization of EF24 and the activity of two key transcription factors, AP-1 and NF-κB, involved in complex cellular responses of cell survival and death. Methods: Cytotoxic activity of various drugs was evaluated using a Neutral Red Dye assay. Cellular localization of biotinylated EF24 (active and reduced EF24 (inactive was determined using light and confocal microscopy. Measurement of transcription factor binding was carried out using Transfactor ELISA kits (BD Clontech, Palo Alto, CA. Gene microarray processing was performed at Expression Analysis, Inc (Durham, NC using Affymetrix Human U133A Gene Chips.Results: In this study, we demonstrated that EF24 and UBS109 exhibit much more potent cytotoxic activity against pancreatic cancer than the current standard chemotherapeutic agent gemcitabine. EF24, rapidly localizes to the cell nucleus. The compound modulates the DNA binding activity of NF-κB and AP-1 in MDA-MB-231 human breast cancer cells and DU-145 human prostate cancer cells. Immunohistochemical studies utilizing biotinylated-EF24 and chemically-reduced EF24 show that the unsaturated compound and biotinylated EF24, but not reduced EF24, translocates to the nucleus within 30 minutes after the addition of drug. Through a gene microarray study, EF24 is shown to affect genes directly involved in cytoprotection, tumor growth, angiogenesis, metastasis and apoptosis. Conclusion: EF24 and UBS109 warrant further investigation for development of pancreatic cancer therapy. The dualistic modulations of gene expression may be a manifestation of the cell responses for survival against oxidative stress by EF24. However, the cytotoxic action of EF24 ultimately prevails to kill the cells.

  3. Korean Red Ginseng Extract Enhances the Anticancer Effects of Imatinib Mesylate Through Abrogation p38 and STAT5 Activation in KBM-5 Cells.

    Science.gov (United States)

    Jung, Sang Yoon; Kim, Chulwon; Kim, Wan-Seok; Lee, Seok-Geun; Lee, Jun-Hee; Shim, Bum Sang; Kim, Sung-Hoon; Ahn, Kyoo Seok; Ahn, Kwang Seok

    2015-07-01

    Although imatinib mesylate (IM) in the treatment of chronic myelogenous leukemia (CML) remains the best example of successful targeted therapy, majority of patients with CML suffer its toxicity profile and develop chemoresistance to existing therapeutic agents. Thus, there is a need to develop novel alternative therapies for the treatment of CML. Here, we investigated whether Korean red ginseng extract (KRGE) could suppress the proliferation and induce chemosensitization in human CML cells. Also, we used a human phospho-antibody array containing 46 antibodies against signaling molecules to examine a subset of phosphorylation events after treatment. Korean red ginseng extract broadly suppressed the proliferation of five different cell lines, but KRGE was found to be the most potent inducer of apoptosis against KBM-5 cells. It also abrogated the expression of Bcl-2 (B-cell lymphoma 2), Bcl-xL (B-cell lymphoma-extra large), survivin, inhibitors of apoptosis protein 1/2, COX-2 (Cyclooxygenase-2), cyclin D1, matrix metalloproteinase-9, and VEGF (Vascular endothelial growth factor), as well as upregulated the expression of pro-apoptotic gene products. Interestingly, KRGE also enhanced the cytotoxic and apoptotic effect of IM in KBM-5 cells. The combination treatment of KRGE and IM caused pronounced suppression of p38 and signal transducer and activator of transcription 5 phosphorylation and induced phosphorylation of p53 compared with the individual treatment. Our results demonstrate that KRGE can enhance the anticancer activity of IM and may have a substantial potential in the treatment of CML. PMID:25857479

  4. Treatment Combining X-Irradiation and a Ribonucleoside Anticancer Drug, TAS106, Effectively Suppresses the Growth of Tumor Cells Transplanted in Mice

    International Nuclear Information System (INIS)

    Purpose: To examine the in vivo antitumor efficacy of X-irradiation combined with administration of a ribonucleoside anticancer drug, 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl)cytosine (TAS106, ECyd), to tumor cell-transplanted mice. Methods and Materials: Colon26 murine rectum adenocarcinoma cells and MKN45 human gastric adenocarcinoma cells were inoculated into the footpad in BALB/c mice and severe combined immunodeficient mice, respectively. They were treated with a relatively low dose of X-irradiation (2 Gy) and low amounts of TAS106 (0.1 mg/kg and 0.5 mg/kg). The tumor growth was monitored by measuring the tumor volume from Day 5 to Day 16 for Colon26 and from Day 7 to Day 20 for MKN45. Histologic analyses for proliferative and apoptotic cells in the tumors were performed using Ki-67 immunohistochemical and terminal deoxynucleotidyl transferase-mediated nick end labeling staining. The expression of survivin, a key molecule related to tumor survival, was assessed by quantitative polymerase chain reaction and immunohistochemical analysis. Results: When X-irradiation and TAS106 treatment were combined, significant inhibition of tumor growth was observed in both types of tumors compared with mice treated with X-irradiation or TAS106 alone. Marked inhibition of tumor growth was observed in half of the mice that received the combined treatment three times at 2-day intervals. Parallel to these phenomena, the suppression of survivin expression and appearance of Ki-67-negative and apoptotic cells were observed. Conclusions: X-irradiation and TAS106 effectively suppress tumor growth in mice. The inhibition of survivin expression by TAS106 is thought to mainly contribute to the suppression of the tumor growth

  5. Molecular Basis of the Anti-Cancer Effects of Genistein Isoflavone in LNCaP Prostate Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Hartmann J

    2011-03-01

    Full Text Available Background: Prostate cancer is the most common form of non-skin cancer within the United States and the second leading cause of cancer deaths. Survival rates for the advanced disease remain relatively low, and conventional treatments may be accompanied by significant side effects. As a result, current research is aimed at alternative or adjuvant treatments that will target components of the signal transduction, cell-cycle and apoptosis pathways, to induce cell death with little or no toxic side effects to the patient. In this study, we investigated the effect of genistein isoflavone, a soy derivative, on expression levels of genes involved in these pathways. The mechanism of genistein-induced cell death was also investigated. The chemosensitivity of the LNCaP prostate cancer cells to genistein was investigated using ATP and MTS assays, and a caspase binding assay was used to determine apoptosis induction. Several molecular targets were determined using cDNA microarray and RT-PCR analysis.Results: The overall data revealed that genistein induces cell death in a time- and dose-dependent manner, and regulates expression levels of several genes involved in carcinogenesis and immunity. Several cell-cycle genes were down-regulated, including the mitotic kinesins, cyclins and cyclin-dependent kinases. Various members of the Bcl-2 family of apoptotic proteins were also affected. The DefB1 and the HLA membrane receptor genes involved in immunogenicity were also up-regulated.Conclusion: The results indicate that genistein inhibits growth of the hormone-dependent prostate cancer cells, LNCaP, via apoptosis induction through regulation of some of the genes involved in carcinogenesis of many tumors, and immunogenicity. This study augments the potential phytotherapeutic and immunotherapeutic significance of genistein isoflavone.

  6. Characterization of synergistic anti-cancer effects of docosahexaenoic acid and curcumin on DMBA-induced mammary tumorigenesis in mice

    International Nuclear Information System (INIS)

    The major obstacles to the successful use of individual nutritional compounds as preventive or therapeutic agents are their efficacy and bioavailability. One approach to overcoming this problem is to use combinations of nutrients to induce synergistic effects. The objective of this research was to investigate the synergistic effects of two dietary components: docosahexaenoic acid (DHA), an omega-3 fatty acid present in cold-water fish, and curcumin (CCM), an herbal nutrient present in turmeric, in an in vivo model of DMBA-induced mammary tumorigenesis in mice. We used the carcinogen DMBA to induce breast tumors in SENCAR mice on control, CCM, DHA, or DHA + CCM diets. Appearance and tumor progression were monitored daily. The tumors were harvested 15 days following their first appearance for morphological and immunohistological analysis. Western analysis was performed to determine expression of maspin and survivin in the tumor tissues. Characterization of tumor growth was analyzed using appropriate statistical methods. Otherwise all other results are reported as mean ± SD and analyzed with one-way ANOVA and Tukey’s post hoc procedure. Analysis of gene microarray data indicates that combined treatment with DHA + CCM altered the profile of “PAM50” genes in the SK-BR-3 cell line from an ER-/Her-2+ to that resembling a “normal-like” phenotype. The in vivo studies demonstrated that DHA + CCM treatment reduced the incidence of breast tumors, delayed tumor initiation, and reduced progression of tumor growth. Dietary treatment had no effect on breast size development, but tumors from mice on a control diet (untreated) were less differentiated than tumors from mice fed CCM or DHA + CCM diets. The synergistic effects also led to increased expression of the pro-apoptotic protein, maspin, but reduced expression of the anti-apoptotic protein, survivin. The SK-BR-3 cells and DMBA-induced tumors, both with an ER- and Her-2+ phenotype, were affected by the synergistic

  7. Effects of commonly consumed fruit juices and carbohydrates on redox status and anticancer biomarkers in female rats

    DEFF Research Database (Denmark)

    Breinholt, Vibeke M.; Nielsen, Salka E.; Knuthsen, Pia;

    2003-01-01

    diet. However, no effects were observed on hepatic glutathione S-transferase or quinone reductase activities, plasma redox status, or the activity of red blood cell antioxidant enzymes. Overall, the results of the present study suggest that commonly consumed fruit juices can alter lipid and protein...... average carbohydrate levels in the employed fruit juices. None of the fruit juices were found to affect the activities of antioxidant enzymes in red blood cells or hepatic glutathione S-transferase. Hepatic quinone reductase activity, on the other hand, was significantly increased by grape-fruit juice...

  8. The Combined Use of Known Antiviral Reverse Transcriptase Inhibitors AZT and DDI Induce Anticancer Effects at Low Concentrations

    Directory of Open Access Journals (Sweden)

    Thomas Aschacher

    2012-01-01

    Full Text Available A hallmark of tumor cell survival is the maintenance of elongated telomeres. It is known that antiviral reverse transcriptase inhibitors (RTIs such as azidothymidine (AZT and didanosine (ddI lead to telomere shortening at high, potentially toxic concentrations. We hypothesized that those drugs might have synergistic effects enabling successful therapy with low, nontoxic concentrations. Biologic effects of AZT and ddI were analyzed at concentrations that correspond to minimal plasma levels achieved during human immunodeficiency virus therapy. Long-term coapplication of low-dose AZT and ddI induced a significant shortening of telomeres in the tumor cell lines HCT-116, SkMel-28, MelJuso, and Jurkat. Treatment of cells with both RTI, but not with single RTI, led to a significant accumulation of γH2AX, to p53 phosphorylation, and to cell apoptosis in all cell lines. Oral low-dose dual RTI application but not low-dose single RTI application was associated with a significantly reduced tumor growth of HCT-116 cells in mice. This antiproliferative activity of the combined use of AZT and ddI at low, clinically applicable concentrations warrants clinical testing in human solid cancer.

  9. First report on Cydonia oblonga Miller anticancer potential: differential antiproliferative effect against human kidney and colon cancer cells.

    Science.gov (United States)

    Carvalho, Márcia; Silva, Branca M; Silva, Renata; Valentão, Patrícia; Andrade, Paula B; Bastos, Maria L

    2010-03-24

    The present study reports the phenolic profile and antiproliferative properties of quince (Cydonia oblonga Miller) leaf and fruit (pulp, peel, and seed) against human kidney and colon cancer cells. The phenolic profiles of quince methanolic extracts were determined by high-performance liquid chromatography (HPLC)/diode array detector (DAD). 5-O-Caffeoylquinic acid was always one of the two major phenolic compounds present in all extracts, except for seed. Our results revealed that quince leaf and fruit extracts exhibited distinctive antiproliferative activities. The extracts from quince leaf showed concentration-dependent growth inhibitory activity toward human colon cancer cells (IC(50) = 239.7 +/- 43.2 microg/mL), while no effect was observed in renal adenocarcinoma cells. Concerning the fruit, seed extracts exhibited no effect on colon cancer cell growth, whereas strong antiproliferative efficiency against renal cancer cells was observed for the highest concentration assayed (500 microg/mL). The antiproliferative activity of pulp and peel extracts was low or absent in the selected range of extract concentrations. This is the first report showing that C. oblonga may be useful as a cancer chemopreventive and/or chemotherapeutic agent. PMID:20192210

  10. DT-13, a saponin monomer of dwarf lilyturf tuber, induces autophagy and potentiates anti-cancer effect of nutrient deprivation.

    Science.gov (United States)

    Li, Hongyang; Sun, Li; de Carvalho, Evandro Lopes; Li, Xinxin; Lv, Xiaodan; Khan, Ghulam Jilany; Semukunzi, Herve; Yuan, Shengtao; Lin, Sensen

    2016-06-15

    Metabolic stress induces autophagy as a protective mechanism in tumorigenesis and development. Conversely, excessive autophagy in nutrient-deprived cancer cells would be beneficial for cancer therapy. DT-13, the saponin monomer 13 of the Dwarf lilyturf tuber, inhibited tumor metastasis and angiogenesis in previous studies. However, there is scarcity of data regarding the effect of DT-13 on autophagy process. Here, we demonstrated that DT-13 induced autophagy in human cancer cell lines and caused significant cell apoptosis under nutrient starvation. We firstly showed that DT-13 increased the accumulation of GFP-LC3 puncta and induced the expression of LC3-II in a dose- and time-dependent manner. DT-13 also upregulated the expression of Beclin-1, Atg-3 and Atg-7, and induced autophagic flux in human gastric cancer BGC-823 cells. We next found that low-toxic concentrations of DT-13 significantly induced apoptosis under nutrient deprivation. We finally demonstrated that the PI3K/Akt/mTOR signal pathway was involved in the cytotoxic effect of DT-13. Our data indicated that DT-13 was a novel autophagy inducer and might be considered in future treatment of cancer. PMID:27079642

  11. 'Smartening' anticancer therapeutic nanosystems using biomolecules.

    Science.gov (United States)

    Núñez-Lozano, Rebeca; Cano, Manuel; Pimentel, Belén; de la Cueva-Méndez, Guillermo

    2015-12-01

    To be effective, anticancer agents must induce cell killing in a selective manner, something that is proving difficult to achieve. Drug delivery systems could help to solve problems associated with the lack of selectivity of classical chemotherapeutic agents. However, to realize this, such systems must overcome multiple physiological barriers. For instance, they must evade surveillance by the immune system, attach selectively to target cells, and gain access to their interior. Furthermore, there they must escape endosomal entrapment, and release their cargoes in a controlled manner, without affecting their functionality. Here we review recent efforts aiming at using biomolecules to confer these abilities to bare nanoparticles, to transform them into smart anticancer therapeutic nanosystems. PMID:26277646

  12. Age-related transcription levels of KU70, MGST1 and BIK in CD34+ hematopoietic stem and progenitor cells.

    Science.gov (United States)

    Prall, Wolf C; Czibere, Akos; Jäger, Marcus; Spentzos, Dimitrios; Libermann, Towia A; Gattermann, Norbert; Haas, Rainer; Aivado, Manuel

    2007-09-01

    Despite the known longevity of human hematopoietic stem and progenitor cells (HSC), numerous functional impairments of these cells can be observed in an age-dependent manner. However, the molecular alterations associated with aging of HSC are largely unknown. Therefore, we scrutinized gene expression patterns of HSC from newborn, young and old healthy donors. CD34+ HSC were isolated via immuno-magnetic separation and evaluated by FACS analysis. We performed cDNA macroarray analyses on a first set of CD34+ samples (n=13). We found the genes encoding KU-antigen 70 kD (KU70), microsomal glutathione S-transferase 1 (MGST1) and BCL2-interacting killer (BIK) to possess age-related mRNA expression levels. KU70 is a DNA repair gene and part of the DNA-dependent protein kinase (DNA-PK) complex. Its expression was negatively correlated with donor age showing highest expression levels in newborn, 2.6-fold lower levels in young and 6.3-fold lower levels in old donors. The transcription levels of MGST1, a gene protecting against oxidative stress, progressively increased with age. Expression was lowest in newborn, 2.6-fold higher in young and 4.3-fold higher in old donors. BIK is a proapoptotic gene and its expression was positively correlated with donor age: lowest in newborn, 1.8-fold higher in young and 4.1-fold higher in old donors. These findings were confirmed with an independent, second set of CD34+ samples (n=16) by means of quantitative real-time RT-PCR. Elucidation of age-dependent molecular alterations in healthy HSC facilitate a better understanding of functional impairments in hematopoiesis and may become valuable for anti-aging drug development and the emerging field of regenerative medicine. PMID:17714764

  13. Abscisic acid enhances tolerance of wheat seedlings to drought and regulates transcript levels of genes encoding ascorbate-glutathione biosynthesis.

    Science.gov (United States)

    Wei, Liting; Wang, Lina; Yang, Yang; Wang, Pengfei; Guo, Tiancai; Kang, Guozhang

    2015-01-01

    Glutathione (GSH) and ascorbate (ASA) are associated with the abscisic acid (ABA)-induced abiotic tolerance in higher plant, however, its molecular mechanism remains obscure. In this study, exogenous application (10 μM) of ABA significantly increased the tolerance of seedlings of common wheat (Triticum aestivum L.) suffering from 5 days of 15% polyethylene glycol (PEG)-stimulated drought stress, as demonstrated by increased shoot lengths and shoot and root dry weights, while showing decreased content of hydrogen peroxide (H2O2) and malondialdehyde (MDA). Under drought stress conditions, ABA markedly increased content of GSH and ASA in both leaves and roots of ABA-treated plants. Temporal and spatial expression patterns of eight genes encoding ASA and GSH synthesis-related enzymes were measured using quantitative real-time reverse transcription polymerase chain reaction (qPCR). The results showed that ABA temporally regulated the transcript levels of genes encoding ASA-GSH cycle enzymes. Moreover, these genes exhibited differential expression patterns between the root and leaf organs of ABA-treated wheat seedlings during drought stress. These results implied that exogenous ABA increased the levels of GSH and ASA in drought-stressed wheat seedlings in time- and organ-specific manners. Moreover, the transcriptional profiles of ASA-GSH synthesis-related enzyme genes in the leaf tissue were compared between ABA- and salicylic acid (SA)-treated wheat seedlings under PEG-stimulated drought stress, suggesting that they increased the content of ASA and GSH by differentially regulating expression levels of ASA-GSH synthesis enzyme genes. Our results increase our understanding of the molecular mechanism of ABA-induced drought tolerance in higher plants. PMID:26175737

  14. Anticancer Efficacy of Polyphenols and Their Combinations

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    Aleksandra Niedzwiecki

    2016-09-01

    Full Text Available Polyphenols, found abundantly in plants, display many anticarcinogenic properties including their inhibitory effects on cancer cell proliferation, tumor growth, angiogenesis, metastasis, and inflammation as well as inducing apoptosis. In addition, they can modulate immune system response and protect normal cells against free radicals damage. Most investigations on anticancer mechanisms of polyphenols were conducted with individual compounds. However, several studies, including ours, have indicated that anti-cancer efficacy and scope of action can be further enhanced by combining them synergistically with chemically similar or different compounds. While most studies investigated the anti-cancer effects of combinations of two or three compounds, we used more comprehensive mixtures of specific polyphenols and mixtures of polyphenols with vitamins, amino acids and other micronutrients. The mixture containing quercetin, curcumin, green tea, cruciferex, and resveratrol (PB demonstrated significant inhibition of the growth of Fanconi anemia head and neck squamous cell carcinoma and dose-dependent inhibition of cell proliferation, matrix metalloproteinase (MMP-2 and -9 secretion, cell migration and invasion through Matrigel. PB was found effective in inhibition of fibrosarcoma HT-1080 and melanoma A2058 cell proliferation, MMP-2 and -9 expression, invasion through Matrigel and inducing apoptosis, important parameters for cancer prevention. A combination of polyphenols (quercetin and green tea extract with vitamin C, amino acids and other micronutrients (EPQ demonstrated significant suppression of ovarian cancer ES-2 xenograft tumor growth and suppression of ovarian tumor growth and lung metastasis from IP injection of ovarian cancer A-2780 cells. The EPQ mixture without quercetin (NM also has shown potent anticancer activity in vivo and in vitro in a few dozen cancer cell lines by inhibiting tumor growth and metastasis, MMP-2 and -9 secretion, invasion

  15. Oncolytic viruses as anticancer vaccines

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    Norman eWoller

    2014-07-01

    Full Text Available Oncolytic virotherapy has shown impressive results in preclinical studies and first promising therapeutic outcomes in clinical trials as well. Since viruses are known for a long time as excellent vaccination agents, oncolytic viruses are now designed as novel anticancer agents combining the aspect of lysis-dependent cytoreductive activity with concomitant induction of antitumoral immune responses. Antitumoral immune activation by oncolytic virus infection of tumor tissue comprises both, immediate effects of innate immunity and also adaptive responses for long lasting antitumoral activity which is regarded as the most prominent challenge in clinical oncology. To date, the complex effects of a viral tumor infection on the tumor microenvironment and the consequences for the tumor-infiltrating immune cell compartment are poorly understood. However, there is more and more evidence that a tumor infection by an oncolytic virus opens up a number of options for further immunomodulating interventions such as systemic chemotherapy, generic immunostimulating strategies, dendritic cell-based vaccines, and antigenic libraries to further support clinical efficacy of oncolytic virotherapy.

  16. The synergistic anticancer effect of cisplatin combined with Oldenlandia diffusa in osteosarcoma MG-63 cell line in vitro

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    Pu F

    2016-01-01

    Full Text Available Feifei Pu,1 Fengxia Chen,2 Song Lin,1 Songfeng Chen,1 Zhicai Zhang,1 Baichuan Wang,1 Zengwu Shao1 1Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 2Department of Medical Oncology, General Hospital of The Yangtze River Shipping, Wuhan, Hubei, People’s Republic of China Background: Oldenlandia diffusa (OD is a well-known traditional Chinese medicine, which is used to prevent and treat many disorders, especially cancers. However, its role in osteosarcoma has not been well understood. Here, we used OD and cisplatin individually and combined in osteosarcoma MG-63 cell to explore whether OD could induce cellular apoptosis and suppress the ability of proliferation and invasion of osteosarcoma MG-63 cell.Methods: The changes of cellular shape were analyzed by optical microscopy. 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazoliumbromide assay was used to analyze cell survival rate in vitro. Flow cytometry was performed to detect cell cycle and cell death. Scratch migration assay was used to evaluate cell migration and invasion. Western blot was performed to determine the expression levels of pro-apoptotic and anti-apoptotic protein.Results: In this study, we found that the survival rate reduced significantly in the combined group compared with the individual group and control group. The apoptosis-inducing effect of combined application was much more significant than that of individual application. The invasion ability of combined application was significantly lower than that of the individual application. In the combined group, there were high expression levels of pro-apoptotic protein and low expression of anti-apoptotic protein. Cell-cycle analysis showed a change in the cell-cycle distribution and arrested cells in G2-M phase.Conclusion: In this study, we found that OD inhibited proliferation and induced apoptosis in the human osteosarcoma MG-63 cell line in a time-dependent and dose

  17. A REVIEW: HERBS USED AS ANTICANCER AGENTS

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    Badri Nagarani

    2011-01-01

    Full Text Available Herbs are the plants which will have desirable odour, taste and other medical uses. Anti-cancer agents are effective in cancer treatment. Here an attempt has been made to review some herbs used for the prevention and treatment of cancer. These herbs were found for posses anticancer, cytotoxic or antioxidant activity in various pre-clinical or clinical studies. Cancer is a disease in which body cells become abnormal and divide without control. Cancer cell may invade nearby tissues and they may spread through the blood stream & lymphatic system to other parts of the body. The search for anticancer agents from the plant sources alkaloids in earnest in the 1950s such as Vincristine, Vinblastine and the isolation of cytotoxic Podophyllotoxins will reduce white blood cell count and caused bone marrow depression in rats. Roots, leaves, stem, root, bark and fruity of the plant herbs are used in the treatment of cancer. The dietary antioxidants having anti carcinogenic property are in demand. Identification and characterization of these anti-carcinogens in the diet can be used for reducing the risk of human cancer. Tea (Camellia thea an evergreen plant contains antioxidants which prevent and repair cellular damage caused by reactive free radicals. Supervitamin drinks containing a combination of Hordeum vulgare, Medicago sativa and Spirulina enhances the activity of immune cells against cancer. Mentha species containing antioxidants prevent reocurrence of cancer.

  18. Autogenous regulation of the EcoRII methylase gene at the transcriptional level: effect of 5-azacytidine.

    OpenAIRE

    Som, S; Friedman, S.

    1993-01-01

    mRNA of the EcoRII methylase (M.EcoRII), a type II modification enzyme, was induced when Escherichia coli carrying a cloned M.EcoRII gene was exposed to the bacteriocidal drug 5-azacytidine. Induction occurred only when transcription was initiated from its own promoter. When the 5' promoter sequences were deleted or replaced with the lac promoter sequences, no induction occurred. The induction was independent of the template DNA level, but the presence of an intact M.EcoRII protein was a requ...

  19. The Study on Anti-cancer Effects of Distilling Fresh-ginseng Herbal acupuncture against implanted Sarcoma-180 in vivo and A549 human epithelial lung cancer cells in vitro

    Directory of Open Access Journals (Sweden)

    Hae-Young Jang

    2004-12-01

    Full Text Available Objectives : This study was to investigate the anti-cancer effects of herbal acupuncture with distilled fresh ginseng. The herbal acupuncture was injected to Chung-wan(C.V12 and Wisu(BL21 of mice that were subjected to Sarcoma-180 abdominal cancer cell and A549 human epithelial lung cancer cells in vitro. Methods : Anti-cancer effects of distilled fresh ginseng herbal acupuncture were tested by measruing Cox, Bcl-2, and Bax by using RT-PCR in A549 human epithelial lung cancer cells in vitro. And four weeks old Balb/c line male mice weighing around 20±3g were used to measure survival rate and anti-cancer effect to outputs of interleukin-2 and interleukin-4 using flow cytometry, possibility of mRNA menifestation using RT-PCR, and Cox mRNA. The results are as follows. Results : 1. In measuring mRNA menifestation in Cox, Bcl-2, and Bax by using RT-PCR in A549 human epithelial lung cancer cells in vitro, the result showed that fresh ginseng decreased Cox-2 which is directly involved in inflammation process. 2. Survival rate was measured in an anti-cancer effect experiment against Sarcoma-180 abdorminal cancer. Median survival time of controlled group was 27 days, of experiment group I was 21 days, and of experiment group II was 27 days. Therefore, experiment group I showed -22.2% increase in survival rate and experiment group II showed no difference compare to controlled group. 3. There was no difference between condition group and controlled and experiment group in measuring outputs of interleukin-2 and interleukin 4 by using flow cytometry 4. In measuring outputs of interleukin-2 by using ELISA, there was no significant difference between condition group and controlled group and there was decrease in experiment group II compared to conditioned and controlled group. 5. In measuring cytokine mRNA menifestation by using RT-PCR, experiment group I showed increase of mRNA menifestation in interleukin-2,4 and interferon-γ and experiment group II showed

  20. Synergistic effect of pH-responsive folate-functionalized poloxamer 407-TPGS-mixed micelles on targeted delivery of anticancer drugs

    OpenAIRE

    Butt AM; Mohd Amin MC; Katas H

    2015-01-01

    Adeel Masood Butt, Mohd Cairul Iqbal Mohd Amin, Haliza Katas Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia Background: Doxorubicin (DOX), an anthracycline anticancer antibiotic, is used for treating various types of cancers. However, its use is associated with toxicity to normal cells and development of resistance due to overexpression of drug efflux pumps. Poloxamer 407 (P407) and vitamin E TPGS (d-α-tocopheryl poly...

  1. Classification of current anticancer immunotherapies

    Science.gov (United States)

    Vacchelli, Erika; Pedro, José-Manuel Bravo-San; Buqué, Aitziber; Senovilla, Laura; Baracco, Elisa Elena; Bloy, Norma; Castoldi, Francesca; Abastado, Jean-Pierre; Agostinis, Patrizia; Apte, Ron N.; Aranda, Fernando; Ayyoub, Maha; Beckhove, Philipp; Blay, Jean-Yves; Bracci, Laura; Caignard, Anne; Castelli, Chiara; Cavallo, Federica; Celis, Estaban; Cerundolo, Vincenzo; Clayton, Aled; Colombo, Mario P.; Coussens, Lisa; Dhodapkar, Madhav V.; Eggermont, Alexander M.; Fearon, Douglas T.; Fridman, Wolf H.; Fučíková, Jitka; Gabrilovich, Dmitry I.; Galon, Jérôme; Garg, Abhishek; Ghiringhelli, François; Giaccone, Giuseppe; Gilboa, Eli; Gnjatic, Sacha; Hoos, Axel; Hosmalin, Anne; Jäger, Dirk; Kalinski, Pawel; Kärre, Klas; Kepp, Oliver; Kiessling, Rolf; Kirkwood, John M.; Klein, Eva; Knuth, Alexander; Lewis, Claire E.; Liblau, Roland; Lotze, Michael T.; Lugli, Enrico; Mach, Jean-Pierre; Mattei, Fabrizio; Mavilio, Domenico; Melero, Ignacio; Melief, Cornelis J.; Mittendorf, Elizabeth A.; Moretta, Lorenzo; Odunsi, Adekunke; Okada, Hideho; Palucka, Anna Karolina; Peter, Marcus E.; Pienta, Kenneth J.; Porgador, Angel; Prendergast, George C.; Rabinovich, Gabriel A.; Restifo, Nicholas P.; Rizvi, Naiyer; Sautès-Fridman, Catherine; Schreiber, Hans; Seliger, Barbara; Shiku, Hiroshi; Silva-Santos, Bruno; Smyth, Mark J.; Speiser, Daniel E.; Spisek, Radek; Srivastava, Pramod K.; Talmadge, James E.; Tartour, Eric; Van Der Burg, Sjoerd H.; Van Den Eynde, Benoît J.; Vile, Richard; Wagner, Hermann; Weber, Jeffrey S.; Whiteside, Theresa L.; Wolchok, Jedd D.; Zitvogel, Laurence; Zou, Weiping

    2014-01-01

    During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into “passive” and “active” based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches. PMID:25537519

  2. Gallic acid induces apoptosis and enhances the anticancer effects of cisplatin in human small cell lung cancer H446 cell line via the ROS-dependent mitochondrial apoptotic pathway.

    Science.gov (United States)

    Wang, Ruixuan; Ma, Lijie; Weng, Dan; Yao, Jiahui; Liu, Xueying; Jin, Faguang

    2016-05-01

    Small cell lung cancer (SCLC) is the most aggressive lung cancer subtype and accounts for more than 15% of all lung cancer cases. Cisplatin [cis-diamminedichloroplatinum (CDDP)]-based combination chemotherapy is the cornerstone for all stages of SCLC. However, acquired multidrug resistance (MDR) and intolerable toxicities lead to a high mortality rate in SCLC patients. Gallic acid [3,4,5-trihydroxybenzoic acid (GA)] is a natural botanic phenolic compound which can induce cell apoptosis in several types of cancers. In the present study, we aimed to explore the anticancer effects of GA on human SCLC H446 cells and its promotive effects on the anticancer activities of cisplatin. The viability of the H446 cells was analyzed by MTT assay. Morphological changes in the H446 cells were observed under an inverted microscope. Apoptosis induction was determined by Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining. The level of reactive oxygen species (ROS) was assessed by 2'7'-dichlorofluorescein diacetate (DCFH‑DA), mitochondrial membrane potential (MMP) by JC-1, and western blotting was used to examine the expression of mitochondrial apoptosis-related proteins. The results showed that both GA and cisplatin changed the morphology, inhibited the growth and induced apoptosis in the H446 cells by inducing generation of ROS, disruption of MMP, downregulation of XIAP expression, and upregulation of Bax, Apaf-1, DIABLO and p53 expression. More importantly, GA combined with cisplatin exhibited synergistic effects on inducing of these pro-apoptotic mediators and modulating the activation of apoptosis-related molecules. However, inhibition of the generation of ROS by N-acetyl-l-cysteine (NAC), a specific ROS inhibitor, reversed the cell apoptosis induced by cisplatin combined with GA. In conclusion, the results from the present study revealed that GA exhibited an anticancer effect on human SCLC H446 cells and enhanced the antitumor activities of cisplatin

  3. Reduction of graphene oxide by resveratrol: a novel and simple biological method for the synthesis of an effective anticancer nanotherapeutic molecule

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    Gurunathan S

    2015-04-01

    Full Text Available Sangiliyandi Gurunathan, Jae Woong Han, Eun Su Kim, Jung Hyun Park, Jin-Hoi Kim Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea Objective: Graphene represents a monolayer or a few layers of sp2-bonded carbon atoms with a honeycomb lattice structure. Unique physical, chemical, and biological properties of graphene have attracted great interest in various fields including electronics, energy, material industry, and medicine, where it is used for tissue engineering and scaffolding, drug delivery, and as an antibacterial and anticancer agent. However, graphene cytotoxicity for ovarian cancer cells is still not fully investigated. The objective of this study was to synthesize graphene using a natural polyphenol compound resveratrol and to investigate its toxicity for ovarian cancer cells.Methods: The successful reduction of graphene oxide (GO to graphene was confirmed by UV-vis and Fourier transform infrared spectroscopy. Dynamic light scattering and scanning electron microscopy were employed to evaluate particle size and surface morphology of GO and resveratrol-reduced GO (RES-rGO. Raman spectroscopy was used to determine the removal of oxygen-containing functional groups from GO surface and to ensure the formation of graphene. We also performed a comprehensive analysis of GO and RES-rGO cytotoxicity by examining the morphology, viability, membrane integrity, activation of caspase-3, apoptosis, and alkaline phosphatase activity of ovarian cancer cells.Results: The results also show that resveratrol effectively reduced GO to graphene and the properties of RES-rGO nanosheets were comparable to those of chemically reduced graphene. Biological experiments showed that GO and RES-rGO caused a dose-dependent membrane leakage and oxidative stress in cancer cells, and reduced their viability via apoptosis confirmed by the upregulation of apoptosis executioner caspase-3.Conclusion: Our data demonstrate a single, simple green

  4. H2S donor, S-propargyl-cysteine, increases CSE in SGC-7901 and cancer-induced mice: evidence for a novel anti-cancer effect of endogenous H2S?

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    Kaium Ma

    Full Text Available BACKGROUND: S-propargyl-cysteine (SPRC, an H(2S donor, is a structural analogue of S-allycysteine (SAC. It was investigated for its potential anti-cancer effect on SGC-7901 gastric cancer cells and the possible mechanisms that may be involved. METHODS AND FINDINGS: SPRC treatment significantly decreased cell viability, suppressed the proliferation and migration of SPRC-7901 gastric cancer cells, was pro-apoptotic as well as caused cell cycle arrest at the G(1/S phase. In an in vivo study, intra-peritoneal injection of 50 mg/kg and 100 mg/kg of SPRC significantly reduced tumor weights and tumor volumes of gastric cancer implants in nude mice, with a tumor growth inhibition rate of 40-75%. SPRC also induced a pro-apoptotic effect in cancer tissues and elevated the expressions of p53 and Bax in tumors and cells. SPRC treatment also increased protein expression of cystathione-γ-lyase (CSE in cells and tumors, and elevated H(2S levels in cell culture media, plasma and tumoral CSE activity of gastric cancer-induced nude mice by 2, 2.3 and 1.4 fold, respectively. Most of the anti-cancer functions of SPRC on cells and tumors were significantly suppressed by PAG, an inhibitor of CSE activity. CONCLUSIONS: Taken together, the results of our study provide insights into a novel anti-cancer effect of H(2S as well as of SPRC on gastric cancer through inducing the activity of a new target, CSE.

  5. Anticancer agents from marine sponges.

    Science.gov (United States)

    Ye, Jianjun; Zhou, Feng; Al-Kareef, Ammar M Q; Wang, Hong

    2015-01-01

    Marine sponges are currently one of the richest sources of anticancer active compounds found in the marine ecosystems. More than 5300 different known metabolites are from sponges and their associated microorganisms. To survive in the complicated marine environment, most of the sponge species have evolved chemical means to defend against predation. Such chemical adaptation produces many biologically active secondary metabolites including anticancer agents. This review highlights novel secondary metabolites in sponges which inhibited diverse cancer species in the recent 5 years. These natural products of marine sponges are categorized based on various chemical characteristics. PMID:25402340

  6. The preventive effect of granisetron on digestive tract symptoms induced by arterial infusion of anticancer and hypertensive agents in combination with radiotherapy. A study of forty patients with bladder cancer

    International Nuclear Information System (INIS)

    Forty patients with bladder cancer who underwent radiotherapy with angiotensin II, a hypertensor, and two cycles of arterial infusion of anticancer chemotherapies, including cisplatin 100 mg/body, were randomly assigned to a granisetron group and a non-granisetron group for comparative study of its prophylactic effect on nausea, vomiting and anorexia. Granisetron proved significantly effective in preventing nausea, as 75% of granisetron-administered patients experienced either only slight nausea or none at all, against only 22.5% in the non-granisetron group. The number of vomiting episodes was zero during the three-day observation period in 28 out of 40 (70%) granisetron-administered patients compared with 6 patients (15%) in the non-granisetron group. A significant difference in prophylactic effect on anorexia was demonstrated between the granisetron and non-granisetron group, indicating that control of alimentary symptoms such as nausea and vomiting influences the severity of anorexia. As to the safety, nausea was lengthened and deteriorated in one patient. Though the physician in charge judged it to be an adverse event too minor to question the safety of granisetron. Thus, granisetron proved to be highly effective and safe in preventing nausea, vomiting and anorexia in patients under concomitant administration of radiotherapy with hypertensor and arterial infusion of anticancer chemotherapies. (author)

  7. Histone deacetylase inhibitors (HDACIs: multitargeted anticancer agents

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    Ververis K

    2013-02-01

    Full Text Available Katherine Ververis,1 Alison Hiong,1 Tom C Karagiannis,1,* Paul V Licciardi2,*1Epigenomic Medicine, Alfred Medical Research and Education Precinct, 2Allergy and Immune Disorders, Murdoch Childrens Research Institute, Melbourne, VIC, Australia*These authors contributed equally to this workAbstract: Histone deacetylase (HDAC inhibitors are an emerging class of therapeutics with potential as anticancer drugs. The rationale for developing HDAC inhibitors (and other chromatin-modifying agents as anticancer therapies arose from the understanding that in addition to genetic mutations, epigenetic changes such as dysregulation of HDAC enzymes can alter phenotype and gene expression, disturb homeostasis, and contribute to neoplastic growth. The family of HDAC inhibitors is large and diverse. It includes a range of naturally occurring and synthetic compounds that differ in terms of structure, function, and specificity. HDAC inhibitors have multiple cell type-specific effects in vitro and in vivo, such as growth arrest, cell differentiation, and apoptosis in malignant cells. HDAC inhibitors have the potential to be used as monotherapies or in combination with other anticancer therapies. Currently, there are two HDAC inhibitors that have received approval from the US FDA for the treatment of cutaneous T-cell lymphoma: vorinostat (suberoylanilide hydroxamic acid, Zolinza and depsipeptide (romidepsin, Istodax. More recently, depsipeptide has also gained FDA approval for the treatment of peripheral T-cell lymphoma. Many more clinical trials assessing the effects of various HDAC inhibitors on hematological and solid malignancies are currently being conducted. Despite the proven anticancer effects of particular HDAC inhibitors against certain cancers, many aspects of HDAC enzymes and HDAC inhibitors are still not fully understood. Increasing our understanding of the effects of HDAC inhibitors, their targets and mechanisms of action will be critical for the

  8. Liposomal formulation of α-tocopheryl maleamide: In vitro and in vivo toxicological profile and anticancer effect against spontaneous breast carcinomas in mice

    International Nuclear Information System (INIS)

    The vitamin E analogue α-tocopheryl succinate (α-TOS) is an efficient anti-cancer drug. Improved efficacy was achieved through the synthesis of α-tocopheryl maleamide (α-TAM), an esterase-resistant analogue of α-tocopheryl maleate. In vitro tests demonstrated significantly higher cytotoxicity of α-TAM towards cancer cells (MCF-7, B16F10) compared to α-TOS and other analogues prone to esterase-catalyzed hydrolysis. However, in vitro models demonstrated that α-TAM was cytotoxic to non-malignant cells (e.g. lymphocytes and bone marrow progenitors). Thus we developed lyophilized liposomal formulations of both α-TOS and α-TAM to solve the problem with cytotoxicity of free α-TAM (neurotoxicity and anaphylaxis), as well as the low solubility of both drugs. Remarkably, neither acute toxicity nor immunotoxicity implicated by in vitro tests was detected in vivo after application of liposomal α-TAM, which significantly reduced the growth of cancer cells in hollow fiber implants. Moreover, liposomal formulation of α-TAM and α-TOS each prevented the growth of tumours in transgenic FVB/N c-neu mice bearing spontaneous breast carcinomas. Liposomal formulation of α-TAM demonstrated anti-cancer activity at levels 10-fold lower than those of α-TOS. Thus, the liposomal formulation of α-TAM preserved its strong anti-cancer efficacy while eliminating the in vivo toxicity found of the free drug applied in DMSO. Liposome-based targeted delivery systems for analogues of vitamin E are of interest for further development of efficient and safe drug formulations for clinical trials.

  9. The anticancer thiosemicarbazones Dp44mT and triapine lack inhibitory effects as catalytic inhibitors or poisons of DNA topoisomerase IIα

    OpenAIRE

    Yalowich, Jack C.; Wu, Xing; Zhang, Rui; Kanagasabai, Ragu; Hornbaker, Marissa; Hasinoff, Brian B

    2012-01-01

    The thiosemicarbazones Dp44mT (di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone) and triapine have potent antiproliferative activity and have been evaluated as anticancer agents. While these compounds strongly bind iron and copper, their mechanism(s) of action are incompletely understood. A recent report (Rao et al., Cancer Research 69:948-957, 2009) suggested that Dp44mT may, in part, exert its cytotoxicity through poisoning of DNA topoisomerase IIα. In the present report, a variety of as...

  10. Synergistic effect of pH-responsive folate-functionalized poloxamer 407-TPGS-mixed micelles on targeted delivery of anticancer drugs

    Directory of Open Access Journals (Sweden)

    Butt AM

    2015-02-01

    Full Text Available Adeel Masood Butt, Mohd Cairul Iqbal Mohd Amin, Haliza Katas Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia Background: Doxorubicin (DOX, an anthracycline anticancer antibiotic, is used for treating various types of cancers. However, its use is associated with toxicity to normal cells and development of resistance due to overexpression of drug efflux pumps. Poloxamer 407 (P407 and vitamin E TPGS (d-α-tocopheryl polyethylene glycol succinate, TPGS are widely used polymers as drug delivery carriers and excipients for enhancing the drug retention times and stability. TPGS reduces multidrug resistance, induces apoptosis, and shows selective anticancer activity against tumor cells. Keeping in view the problems, we designed a mixed micelle system encapsulating DOX comprising TPGS for its selective anticancer activity and P407 conjugated with folic acid (FA for folate-mediated receptor targeting to cancer cells. Methods: FA-functionalized P407 was prepared by carbodiimide crosslinker chemistry. P407-TPGS/FA-P407-TPGS-mixed micelles were prepared by thin-film hydration method. Cytotoxicity of blank micelles, DOX, and DOX-loaded micelles was determined by alamarBlue® assay. Results: The size of micelles was less than 200 nm with encapsulation efficiency of 85% and 73% for P407-TPGS and FA-P407-TPGS micelles, respectively. Intracellular trafficking study using nile red-loaded micelles indicated improved drug uptake and perinuclear drug localization. The micelles show minimal toxicity to normal human cell line WRL-68, enhanced cellular uptake of DOX, reduced drug efflux, increased DOX–DNA binding in SKOV3 and DOX-resistant SKOV3 human ovarian carcinoma cell lines, and enhanced in vitro cytotoxicity as compared to free DOX. Conclusion: FA-P407-TPGS-DOX micelles show potential as a targeted nano-drug delivery system for DOX due to their multiple synergistic factors of selective anticancer

  11. MEDICINAL PLANTS WITH POTENTIAL ANTICANCER ACTIVITIES: A REVIEW

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    Narah Merina

    2012-06-01

    Full Text Available Plants have been the beacon of therapeutic sources for curing diseases from times immemorial. Medicinal plants with their isolated lead molecules are also used as an alternative medicine for treating neoplastic cells. Neoplastic cells are the anomalous proliferation of cells in the body which cause cancer. Diverse efficient compounds derived from natural products have been isolated as anticancer agents. These chemical compounds are formulated with a view to create effective drugs against cancer. Some of the lead molecules isolated from different medicinal plants are already in use to treat cancer and chemotherapeutic side effects. These potential and successful anticancer molecules include Vincristine, Vinblastin, Taxol, Camptothecin and Podophyllotoxin. This paper deals with the selective medicinal plants having anticancer properties which could be further designed to produce cancer curing drugs.

  12. Increased transcript level of poly(ADP-ribose) polymerase (PARP-1) in human tricuspid compared with bicuspid aortic valves correlates with the stenosis severity

    International Nuclear Information System (INIS)

    Highlights: ► Oxidative stress has been implicated in the pathomechanism of calcific aortic valve stenosis. ► We assessed the transcript levels for PARP-1 (poly(ADP-ribose) polymerase), acts as a DNA damage nick sensor in stenotic valves. ► Early stage of diseased tricuspid valves exhibited higher mRNA levels for PARP-1 compared to bicuspid valves. ► The mRNA levels for PARP-1 inversely correlated with the clinical stenosis severity in tricuspid valves. ► Our data demonstrated that DNA damage pathways might be associated with stenosis severity only in tricuspid valves. -- Abstract: Oxidative stress may contribute to the hemodynamic progression of aortic valve stenosis, and is associated with activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) 1. The aim of the present study was to assess the transcriptional profile and the topological distribution of PARP-1 in human aortic valves, and its relation to the stenosis severity. Human stenotic aortic valves were obtained from 46 patients undergoing aortic valve replacement surgery and used for mRNA extraction followed by quantitative real-time PCR to correlate the PARP-1 expression levels with the non invasive hemodynamic parameters quantifying the stenosis severity. Primary isolated valvular interstitial cells (VICs) were used to explore the effects of cytokines and leukotriene C4 (LTC4) on valvular PARP-1 expression. The thickened areas of stenotic valves with tricuspid morphology expressed significantly higher levels of PARP-1 mRNA compared with the corresponding part of bicuspid valves (0.501 vs 0.243, P = 0.01). Furthermore, the quantitative gene expression levels of PARP-1 were inversely correlated with the aortic valve area (AVA) (r = −0.46, P = 0.0469) and AVA indexed for body surface area (BSA) (r = −0.498; P = 0.0298) only in tricuspid aortic valves. LTC4 (1 nM) significantly elevated the mRNA levels of PARP-1 by 2.38-fold in VICs. Taken together, these data suggest that valvular

  13. Evaluating Medicinal Plants for Anticancer Activity

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    Elisha Solowey

    2014-01-01

    Full Text Available Plants have been used for medical purposes since the beginning of human history and are the basis of modern medicine. Most chemotherapeutic drugs for cancer treatment are molecules identified and isolated from plants or their synthetic derivatives. Our hypothesis was that whole plant extracts selected according to ethnobotanical sources of historical use might contain multiple molecules with antitumor activities that could be very effective in killing human cancer cells. This study examined the effects of three whole plant extracts (ethanol extraction on human tumor cells. The extracts were from Urtica membranacea (Urticaceae, Artemesia monosperma (Asteraceae, and Origanum dayi post (Labiatae. All three plant extracts exhibited dose- and time-dependent killing capabilities in various human derived tumor cell lines and primary cultures established from patients’ biopsies. The killing activity was specific toward tumor cells, as the plant extracts had no effect on primary cultures of healthy human cells. Cell death caused by the whole plant extracts is via apoptosis. Plant extract 5 (Urtica membranacea showed particularly strong anticancer capabilities since it inhibited actual tumor progression in a breast adenocarcinoma mouse model. Our results suggest that whole plant extracts are promising anticancer reagents.

  14. Alkaloids Isolated from Natural Herbs as the Anticancer Agents

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    Jin-Jian Lu

    2012-01-01

    Full Text Available Alkaloids are important chemical compounds that serve as a rich reservoir for drug discovery. Several alkaloids isolated from natural herbs exhibit antiproliferation and antimetastasis effects on various types of cancers both in vitro and in vivo. Alkaloids, such as camptothecin and vinblastine, have already been successfully developed into anticancer drugs. This paper focuses on the naturally derived alkaloids with prospective anticancer properties, such as berberine, evodiamine, matrine, piperine, sanguinarine, and tetrandrine, and summarizes the mechanisms of action of these compounds. Based on the information in the literature that is summarized in this paper, the use of alkaloids as anticancer agents is very promising, but more research and clinical trials are necessary before final recommendations on specific alkaloids can be made.

  15. Anti-cancer natural products isolated from chinese medicinal herbs

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    Wu Guosheng

    2011-07-01

    Full Text Available Abstract In recent years, a number of natural products isolated from Chinese herbs have been found to inhibit proliferation, induce apoptosis, suppress angiogenesis, retard metastasis and enhance chemotherapy, exhibiting anti-cancer potential both in vitro and in vivo. This article summarizes recent advances in in vitro and in vivo research on the anti-cancer effects and related mechanisms of some promising natural products. These natural products are also reviewed for their therapeutic potentials, including flavonoids (gambogic acid, curcumin, wogonin and silibinin, alkaloids (berberine, terpenes (artemisinin, β-elemene, oridonin, triptolide, and ursolic acid, quinones (shikonin and emodin and saponins (ginsenoside Rg3, which are isolated from Chinese medicinal herbs. In particular, the discovery of the new use of artemisinin derivatives as excellent anti-cancer drugs is also reviewed.

  16. Anticancer activities of Nigella sativa (black cumin).

    Science.gov (United States)

    Khan, Md Asaduzzaman; Chen, Han-chun; Tania, Mousumi; Zhang, Dian-zheng

    2011-01-01

    Nigella sativa has been used as traditional medicine for centuries. The crude oil and thymoquinone (TQ) extracted from its seeds and oil are effective against many diseases like cancer, cardiovascular complications, diabetes, asthma, kidney disease etc. It is effective against cancer in blood system, lung, kidney, liver, prostate, breast, cervix, skin with much safety. The molecular mechanisms behind its anticancer role is still not clearly understood, however, some studies showed that TQ has antioxidant role and improves body's defense system, induces apoptosis and controls Akt pathway. Although the anti-cancer activity of N. sativa components was recognized thousands of years ago but proper scientific research with this important traditional medicine is a history of last 2∼3 decades. There are not so many research works done with this important traditional medicine and very few reports exist in the scientific database. In this article, we have summarized the actions of TQ and crude oil of N. sativa against different cancers with their molecular mechanisms. PMID:22754079

  17. Conventional anticancer therapeutics and telomere maintenance mechanisms.

    Science.gov (United States)

    Uziel, Orit; Lahav, Meir

    2014-01-01

    The telomere-telomerase system has a unique role in the biology of cancer. Telomere maintenance, mostly affected by the up regulation of telomerase activity, is a prerequisite for perpetuation of malignant cells. This fundamental biologic feature defines telomere maintenance as an attractive therapeutic target for most types of cancer. This review summarizes some critical aspects of telomere biology with special emphasis on the connection to anticancer therapy. In particular, the effects on the telomere - telomerase system of conventional anticancer treatments, including various cytotoxic drugs, targeted biological agents and radiotherapy, and their possible combination with telomerase-directed therapy are discussed. Several potential problems, including side effects and complications inherent to perturbations of telomere biology in normal cells, are also highlighted. In spite of significant progress in this field, there are still several issues that have to be addressed and ultimately resolved in order to obtain a better characterization of the pros and cons of telomerase-directed therapies and, consequently, their clinical relevance. PMID:24975606

  18. Anticancer Activity of Amauroderma rude

    OpenAIRE

    Jiao, Chunwei; Xie, Yi-Zhen; Yang, Xiangling; Li, Haoran; Li, Xiang-Min; Pan, Hong-Hui; Cai, Mian-Hua; Zhong, Hua-Mei; Yang, Burton B.

    2013-01-01

    More and more medicinal mushrooms have been widely used as a miraculous herb for health promotion, especially by cancer patients. Here we report screening thirteen mushrooms for anti-cancer cell activities in eleven different cell lines. Of the herbal products tested, we found that the extract of Amauroderma rude exerted the highest activity in killing most of these cancer cell lines. Amauroderma rude is a fungus belonging to the Ganodermataceae family. The Amauroderma genus contains approxim...

  19. Novel Anticancer Agents from Ascidiacea

    OpenAIRE

    Vervoort, Hélène C.

    1999-01-01

    This thesis presents an effort to contribute to the discovery and development of struc­turally and mechanistically novel anticancer drugs. In order to reach this goal it focusses on the biologically active secondary metabolites of marine invertebrates of the class As­cidiacea (phylum Chordata, subphylum Urochordata (Tunicata), class Ascidacea). Three distinct areas of research were combined. The first part concerns the discovery of two novel, naturally occurring didemnin depsipeptide...

  20. Current developments of coumarin-based anti-cancer agents in medicinal chemistry.

    Science.gov (United States)

    Emami, Saeed; Dadashpour, Sakineh

    2015-09-18

    Cancer is one of the leading health hazards and the prominent cause of death in the world. A number of anticancer agents are currently in clinical practice and used for treatment of various kinds of cancers. There is no doubt that the existing arsenal of anticancer agents is insufficient due to the high incidence of side effects and multidrug resistance. In the efforts to develop suitable anticancer drugs, medicinal chemists have focused on coumarin derivatives. Coumarin is a naturally occurring compound and a versatile synthetic scaffold possessing wide spectrum of biological effects including potential anticancer activity. This review article covers the current developments of coumarin-based anticancer agents and also discusses the structure-activity relationship of the most potent compounds. PMID:26318068

  1. Gene expression profiling of Spodoptera frugiperda hemocytes and fat body using cDNA microarray reveals polydnavirus-associated variations in lepidopteran host genes transcript levels

    Directory of Open Access Journals (Sweden)

    Feyereisen R

    2006-06-01

    Full Text Available Abstract Background Genomic approaches provide unique opportunities to study interactions of insects with their pathogens. We developed a cDNA microarray to analyze the gene transcription profile of the lepidopteran pest Spodoptera frugiperda in response to injection of the polydnavirus HdIV associated with the ichneumonid wasp Hyposoter didymator. Polydnaviruses are associated with parasitic ichneumonoid wasps and are required for their development within the lepidopteran host, in which they act as potent immunosuppressive pathogens. In this study, we analyzed transcriptional variations in the two main effectors of the insect immune response, the hemocytes and the fat body, after injection of filter-purified HdIV. Results Results show that 24 hours post-injection, about 4% of the 1750 arrayed host genes display changes in their transcript levels with a large proportion (76% showing a decrease. As a comparison, in S. frugiperda fat body, after injection of the pathogenic JcDNV densovirus, 8 genes display significant changes in their transcript level. They differ from the 7 affected by HdIV and, as opposed to HdIV injection, are all up-regulated. Interestingly, several of the genes that are modulated by HdIV injection have been shown to be involved in lepidopteran innate immunity. Levels of transcripts related to calreticulin, prophenoloxidase-activating enzyme, immulectin-2 and a novel lepidopteran scavenger receptor are decreased in hemocytes of HdIV-injected caterpillars. This was confirmed by quantitative RT-PCR analysis but not observed after injection of heat-inactivated HdIV. Conversely, an increased level of transcripts was found for a galactose-binding lectin and, surprisingly, for the prophenoloxidase subunits. The results obtained suggest that HdIV injection affects transcript levels of genes encoding different components of the host immune response (non-self recognition, humoral and cellular responses. Conclusion This analysis of the

  2. Quantitative Analysis of the Relative Transcript Levels of Four Chlorophenol Reductive Dehalogenase Genes in Desulfitobacterium hafniense PCP-1 Exposed to Chlorophenols ▿

    OpenAIRE

    Bisaillon, Ariane; Beaudet, Réjean; Lépine, François; Villemur, Richard

    2011-01-01

    Relative to those of unexposed cultures, the transcript levels of the four CprA-type reductive dehalogenase genes (cprA2, cprA3, cprA4, and cprA5) in Desulfitobacterium hafniense PCP-1 were measured in cultures exposed to chlorophenols. In 2,4,6-trichlorophenol-amended cultures, cprA2 and cprA3 were upregulated, as was cprA5, but concomitantly with the appearance of 2,4-dichlorophenol (DCP). In 3,5-DCP-amended cultures, only cprA5 was upregulated. In pentachlorophenol-amended cultures grown f...

  3. Enediyne compounds - new promises in anticancer therapy.

    Science.gov (United States)

    Gredicak, Matija; Jerić, Ivanka

    2007-06-01

    Scientists of all kinds have long been intrigued by the nature, action and potential of natural toxins that possess exceptional antibacterial and anticancer activities. These compounds, named enediynes, are among the most effective chemotherapeutic agents known. Often compared with intelligent weapons, due to the unique structure and sophisticated mechanism by which they destroy double-helical DNA, enediyne antibiotics are nowadays the most promising leaders in the anticancer therapy. Apart from their diversity, enediyne compounds share some structural and functional similarities. One fragment of a structure is responsible for the recognition and transport, another part acts as molecular trigger while the third, reactive enediyne unit, undergoes Bergman cycloaromatization and causes DNA breakage. Members of the enediyne family are already in clinical use to treat various cancers, but more general use is limited by their complex structure, which makes them formidable targets for synthetic chemists. There are three main approaches in the design of new enediyne-related compounds: improvement of enediyne >warheadsenediynes, their mode of action and efforts undertaken to design artificial enediyne-related DNA cleaving agents. PMID:17507311

  4. In vivo anticancer activity of vanillin semicarbazone

    Institute of Scientific and Technical Information of China (English)

    Shaikh M Mohsin Ali; M Abul Kalam Azad; Mele Jesmin; Shamim Ahsan; M Mijanur Rahman; Jahan Ara Khanam; M Nazrul Islam; Sha M Shahan Shahriar

    2012-01-01

    Objective:To evaluate the anticancer activity of vanillin semicarbazone (VSC) against Ehrlich ascites carcinoma (EAC) cells in Swiss albino mice. Methods:The compound VSC at three doses (5, 7.5 and 10 mg/kg i.p.) was administered into the intraperitoneal cavity of the EAC inoculated mice to observe its efficiency by studying the cell growth inhibition, reduction of tumour weight, enhancement of survival time as well as the changes in depleted hematological parameters. All such parameters were also studied with a known standard drug bleomycin at the dose of 0.3 mg/kg (i.p.). Results:Among the doses studied, 10 mg/kg (i.p.) was found to be quite comparable in potency to that of bleomycin at the dose of 0.3 mg/kg (i.p.). The host toxic effects of VSC was found to be negligible. Conclusions: It can be concluded that VSC can therefore be considered as potent anticancer agent.

  5. Use of algae technology for production of biohydrogen from green microalgae. Possibilities for a practical sustainable process and diversity at both species selection, culturing and gene transcript levels

    Energy Technology Data Exchange (ETDEWEB)

    Skjaanes, Kari

    2011-01-15

    Algae technology represents an extensive research field which has developed rapidly over the last decades. The research activities extend from algae cultivation including CO2 capture, production of commercial products such as health food, aquaculture and animal feed, production of valuable metabolites, to conversion of solar energy into energy carriers like bio hydrogen or bio diesel. A combination of several aspects of algae technology into a multidisciplinary process is proposed in this work. Valuable metabolites produced by algae include for example carotenoids, unsaturated fatty acids, vitamins, glycerol, components with medical activities and a number of antioxidants. Many of these are secondary metabolites produced as a response to different forms of environmental stress, and they may function as protection mechanisms to avoid damage to the cells. Bio hydrogen from green microalgae is an expanding field which has made great progress through the last decade. By exposing some species of algae to environmental stress, e.g. by depriving the algae of sulfur in light, it is possible to produce significant amounts of hydrogen gas. However, this technology is still in its infancy, and there is significant potential for technology development and improvement at every level. In this study, the possibility of producing hydrogen from solar energy by using green microalgae is explored at species selection-, culturing- and gene transcription levels. It is demonstrated that there is a considerable number of species currently known to have potential for hydrogen production, and the same is true for production of valuable metabolites. The effects of different stress reactions on production of the valuable components are described, along with the purpose of their production. This knowledge can be used to evaluate the possibilities for producing hydrogen and high value products efficiently in the same process. Hydrogen production under sulfur deprivation is explored in several

  6. Radioactive human cDNA microarray: comparison of anti-cancer effect between 8-chloro-cAMP and 8-chloro-adenosine

    International Nuclear Information System (INIS)

    Eight-chloroadenosine 3.5-monophosphate (8-Cl-cAMP), a site-selective cyclic adenosine 3,5-monophosphate (cAMP) analogue, exhibits growth inhibition in a broad spectrum of cancer cell lines. Nonetheless, there has been a debate as to whether it is a prodrug for its 8-Cl-adenosine metabolite. Using human cDNA microarray, we investigated a pattern of gene regulation under the treatment of 8-Cl-cAMP and 8-Cl-adenosine in PC3M (ATCC CRL-1435; human prostate cancer cell line). The general methodology of arraying is based on the procedures of DeRisi, et al. (Nature Genetics 14: 48, 1996). The gene expression in PC3M by treating 8-Cl-cAMP 8-Cl-adenosine demonstrated a different pattern compared with nontreated control: bifurcated types for up-regulation but a single-directed type for down-regulation. In summary, we demonstrated that the human cDNA microarray is highly likely to be an efficient technology for evaluating the gene regulation of anti-cancer therapeutic agents, such as 8-Cl-cAMP vs. 8-Cl-adenosine, which has been controverted for a long time

  7. Quinones derived from plant secondary metabolites as anti-cancer agents.

    Science.gov (United States)

    Lu, Jin-Jian; Bao, Jiao-Lin; Wu, Guo-Sheng; Xu, Wen-Shan; Huang, Ming-Qing; Chen, Xiu-Ping; Wang, Yi-Tao

    2013-03-01

    Quinones are plant-derived secondary metabolites that present some anti-proliferation and anti-metastasis effects in various cancer types both in vitro and in vivo. This review focuses on the anti-cancer prospects of plant-derived quinones, namely, aloe-emodin, juglone, β-lapachol, plumbagin, shikonin, and thymoquinone. We intend to summarize their anti-cancer effects and investigate the mechanism of actions to promote the research and development of anti-cancer agents from quinones. PMID:22931417

  8. Clinical pharmacology of novel anticancer drug formulations

    NARCIS (Netherlands)

    Stuurman, F.E.

    2013-01-01

    Studies outlined in this thesis describe the impact of drug formulations on pharmacology of anticancer drugs. It consists of four parts and starts with a review describing the mechanisms of low oral bioavailability of anti-cancer drugs and strategies for improvement of the bioavailability. The major

  9. Anticancer biology of Azadirachta indica L (neem): a mini review.

    Science.gov (United States)

    Paul, Rajkumar; Prasad, Murari; Sah, Nand K

    2011-09-15

    Neem (Azadirachta indica), a member of the Meliaceae family, is a fast growing tropical evergreen tree with a highly branched and stout, solid stem. Because of its tremendous therapeutic, domestic, agricultural and ethnomedicinal significance, and its proximity with human culture and civilization, neem has been called "the wonder tree" and "nature's drug store." All parts of this tree, particularly the leaves, bark, seed-oil and their purified products are widely used for treatment of cancer. Over 60 different types of biochemicals including terpenoids and steroids have been purified from this plant. Pre-clinical research work done during the last decade has fine-tuned our understanding of the anticancer properties of the crude and purified products from this plant. The anticancer properties of the plant have been studied largely in terms of its preventive, protective, tumor-suppressive, immunomodulatory and apoptotic effects against various types of cancer and their molecular mechanisms. This review aims at scanning scattered literature on "the anticancer biology of A. indica," related toxicity problems and future perspectives. The cogent data on the anticancer biology of products from A. indica deserve multi-institutional clinical trials as early as possible. The prospects of relatively cheaper cancer drugs could then be brighter, particularly for the under-privileged cancer patients of the world. PMID:21743298

  10. A novel 17 bp indel in the SMAD3 gene alters transcription level, contributing to phenotypic traits in Chinese cattle

    OpenAIRE

    Shi, Tao; Peng, Wenwen; Yan, Jianyu; Cai, Hanfang; Lan, Xianyong; Lei, Chuzhao; Bai, Yueyu; Chen, Hong

    2016-01-01

    SMAD3, the messenger of the transforming growth factor beta (TGF-β) signaling pathway, plays essential roles in myogenesis and osteogenesis and may relate to the regulation of body weight. In this study, a 17 bp indel (NC_007308: g.101893_101909insGAGGATGAGTGCTCCAG) in intron3 of the SMAD3 gene was detected in four Chinese cattle breeds (Qinchuan, Jiaxian, Nanyang and Caoyuan) by using DNA pool sequencing, and its effects on gene expression and growth traits were analyzed in...

  11. Novel Marine Compounds: Anticancer or Genotoxic?

    Directory of Open Access Journals (Sweden)

    Arif Jamal M.

    2004-01-01

    Full Text Available In the past several decades, marine organisms have generously gifted to the pharmaceutical industries numerous naturally bioactive compounds with antiviral, antibacterial, antimalarial, anti-inflammatory, antioxidant, and anticancer potentials. But till date only few anticancer drugs (cytarabine, vidarabine have been commercially developed from marine compounds while several others are currently in different clinical trials. Majority of these compounds were tested in the tumor xenograft models, however, lack of anticancer potential data in the chemical- and/or oncogene-induced pre-initiation animal carcinogenesis models might have cost some of the marine anticancer compounds an early exit from the clinical trials. This review critically discusses importance of preclinical evaluation, failure of human clinical trials with certain potential anticancer agents, the screening tests used, and choice of biomarkers.

  12. Assessment of the transcription levels for the complement activation control system in eutopic endometrium in women with two or more consecutive miscarriages of unknown etiology.

    Directory of Open Access Journals (Sweden)

    Mateusz Mikołajczyk

    2010-11-01

    Full Text Available Human endometrium, deciuda and placenta have been shown to express factors that inhibit the complement activation cascade - decay-accelerating factor (DAF, membrane cofactor protein (MCP and the C3 complement component. In the following study we have analyzed the transcripts levels for DAF, MCP and heparin-binding epidermal growth factor-like growth factor (HB-EGF, the C3 complement component and receptor for vascular endothelial growth factor (VEGFR1 as markers of endometrial unbalance between factors activating the complement system in women with consecutive miscarriages. Study enrolled 30 women with at least two consecutive miscarriages, and 19 healthly women, that comprised the control group. RNA was isolated from endometrial samples. Transcripts levels of DAF and MCP was higher in women with consecutive miscarriages compared to controls, 0.78 vs 5.08 (p<0.001 and 0.25 vs 0.17 (p=0.001 respectively. In consecutive miscarriages group, DAF and MCP expression was correlated with the C3 expression, with r=0.60; p<0.001 and r= 0.40; p=0.03 respectively. Correlation between DAF and C3 was also noted in controls, 0.70; p=0.001. In women with two or more consecutive miscarriages the analysis proved higher expression of genes that encode proteins that inhibit the complement cascade. Further studies are needed to confirm that this might be a reaction to increased presence of the complement factors, which like C3 that are synthesized in the endometrium.

  13. Cholesterol and bile acids regulate cholesterol 7 alpha-hydroxylase expression at the transcriptional level in culture and in transgenic mice.

    Science.gov (United States)

    Ramirez, M I; Karaoglu, D; Haro, D; Barillas, C; Bashirzadeh, R; Gil, G

    1994-04-01

    Cholesterol 7 alpha-hydroxylase (7 alpha-hydroxylase) is the rate-limiting enzyme in bile acid biosynthesis. It is subject to a feedback control, whereby high levels of bile acids suppress its activity, and cholesterol exerts a positive control. It has been suggested that posttranscriptional control plays a major part in that regulation. We have studied the mechanisms by which cholesterol and bile acids regulate expression of the 7 alpha-hydroxylase gene and found it to be solely at the transcriptional level by using two different approaches. First, using a tissue culture system, we localized a liver-specific enhancer located 7 kb upstream of the transcriptional initiation site. We also showed that low-density lipoprotein mediates transcriptional activation of chimeric genes, containing either the 7 alpha-hydroxylase or the albumin enhancer in front of the 7 alpha-hydroxylase proximal promoter, to the same extent as the in vivo cholesterol-mediated regulation of 7 alpha-hydroxylase mRNA. In a second approach, using transgenic mice, we have found that expression of an albumin enhancer-7 alpha-hydroxylase-lacZ fusion gene is restricted to the liver and is regulated by cholesterol and bile acids in a manner quantitatively similar to that of the endogenous gene. We also found, that a liver-specific enhancer is necessary for expression of the rat 7 alpha-hydroxylase gene, in agreement with the tissue culture experiments. Together, these results demonstrate that cholesterol and bile acids regulate the expression of the 7 alpha-hydroxylase gene solely at the transcriptional level. PMID:8139578

  14. In vitro and in vivo Methods for Anticancer Activity Evaluation and Some Indian Medicinal Plants Possessing Anticancer Properties: An Overview

    Directory of Open Access Journals (Sweden)

    Sumitra Chanda

    2013-07-01

    Full Text Available Cancer is a major public health burden in both developed and developing countries. Anticancer activity is the effect of natural and synthetic or biological and chemical agents to reverse, suppress or prevent carcinogenic progression. Several synthetic agents are used to cure the disease but they have their toxicity and hence the research is going on to investigate the plant derived chemotherapeutic agents. Therefore an attempt has been made to review different in vitro and in vivo methods for estimating anticancer properties of natural products from medicinal plants. In this review, 50 anticancer medicinal plants of Indian origin belonging to 35 families are reported along with detailed information regarding part used, extract used, type of the model used, types of tested cancer cell lines, etc. These plants continue to be used against various types of tumours such as sarcoma, lymphoma, carcinoma and leukemia. All these plants are potential candidates for in vivo studies since they are showing good in vitro anticancer activity.

  15. Hypoxia drives apoptosis independently of p53 and metallothionein transcript levels in hemocytes of the whiteleg shrimp Litopenaeus vannamei.

    Science.gov (United States)

    Felix-Portillo, Monserrath; Martínez-Quintana, José A; Arenas-Padilla, Marina; Mata-Haro, Verónica; Gómez-Jiménez, Silvia; Yepiz-Plascencia, Gloria

    2016-10-01

    The cellular mechanisms used by the shrimp Litopenaeus vannamei to respond to hypoxia have been studied from the energetic metabolism and antioxidant angles. We herein investigated the participation of p53 and metallothionein (MT) in the apoptotic process in response to hypoxia in shrimp hemocytes. The Lvp53 or LvMT genes were efficiently silenced by injection of double stranded RNA for p53 or MT. The effects of silencing on apoptosis were measured as caspase-3 activity and flow cytometry in hemocytes after 24 and 48 h of hypoxia (1.5 mg DO L(-1)). Hemocytes from unsilenced animals had significantly higher apoptosis levels upon both times of hypoxia. The apoptotic levels were diminished but not suppressed in dsp53-silenced but not dsMT-silenced hemocytes after 24 h of hypoxia, indicating a contribution of Lvp53 to apoptosis. Apoptosis in normoxia was significantly higher in dsp53-and dsMT-silenced animals compared to the unsilenced controls, pointing to a possible cytoprotective role of LvMT and Lvp53 during the basal apoptotic program in normoxia. Overall, these results indicate that hypoxia augments apoptosis in shrimp hemocytes and high mRNA levels of Lvp53 and LvMT are not necessary for this response. PMID:27459156

  16. Identification of potential anticancer compounds from Oplopanax horridus.

    Science.gov (United States)

    Wang, Chong-Zhi; Zhang, Zhiyu; Huang, Wei-Hua; Du, Guang-Jian; Wen, Xiao-Dong; Calway, Tyler; Yu, Chunhao; Nass, Rachael; Zhao, Jing; Du, Wei; Li, Shao-Ping; Yuan, Chun-Su

    2013-08-15

    Oplopanax horridus is a plant native to North America. Previous reports have demonstrated that this herb has antiproliferative effects on cancer cells but study mostly focused on its extract or fractions. Because there has been limited phytochemical study on this herb, its bioactive compounds are largely unknown. We recently isolated and identified 13 compounds, including six polyynes, three sesquiterpenes, two steroids, and two phenolic acids, of which five are novel compounds. In this study, we systemically evaluated the anticancer effects of compounds isolated from O. horridus. Their antiproliferative effects on a panel of human colorectal and breast cancer cells were determined using the MTS assay. Cell cycle distribution and apoptotic effects were analyzed by flow cytometry. The in vivo antitumor effect was examined using a xenograft tumor model. Among the 13 compounds, strong antiproliferative effects were observed from falcarindiol and a novel compound oplopantriol A. Falcarindiol showed the most potent antiproliferative effects, significantly inducing pro-apoptosis and cell cycle arrest in the S and G2/M phases. The anticancer potential of falcarindiol was further verified in vivo, significantly inhibiting HCT-116 tumor growth in an athymic nude mouse model at 15 mg/kg. We also analyzed the relationship between polyyne structures and their pharmacological activities. We observed that both the terminal hydroxyl group and double bond obviously affected their anticancer potential. Results from this study supplied valuable information for future semi-synthesis of polyyne derivatives to develop novel cancer chemopreventive agents. PMID:23746754

  17. Toward Repurposing Metformin as a Precision Anti-Cancer Therapy Using Structural Systems Pharmacology

    OpenAIRE

    Thomas Hart; Shihab Dider; Weiwei Han; Hua Xu; Zhongming Zhao; Lei Xie

    2016-01-01

    Metformin, a drug prescribed to treat type-2 diabetes, exhibits anti-cancer effects in a portion of patients, but the direct molecular and genetic interactions leading to this pleiotropic effect have not yet been fully explored. To repurpose metformin as a precision anti-cancer therapy, we have developed a novel structural systems pharmacology approach to elucidate metformin’s molecular basis and genetic biomarkers of action. We integrated structural proteome-scale drug target identification ...

  18. Bone-Remodeling Transcript Levels Are Independent of Perching in End-of-Lay White Leghorn Chickens

    Directory of Open Access Journals (Sweden)

    Maurice D. Dale

    2015-01-01

    Full Text Available Osteoporosis is a bone disease that commonly results in a 30% incidence of fracture in hens used to produce eggs for human consumption. One of the causes of osteoporosis is the lack of mechanical strain placed on weight-bearing bones. In conventionally-caged hens, there is inadequate space for chickens to exercise and induce mechanical strain on their bones. One approach is to encourage mechanical stress on bones by the addition of perches to conventional cages. Our study focuses on the molecular mechanism of bone remodeling in end-of-lay hens (71 weeks with access to perches. We examined bone-specific transcripts that are actively involved during development and remodeling. Using real-time quantitative PCR, we examined seven transcripts (COL2A1 (collagen, type II, alpha 1, RANKL (receptor activator of nuclear factor kappa-B ligand, OPG (osteoprotegerin, PTHLH (PTH-like hormone, PTH1R (PTH/PTHLH type-1 receptor, PTH3R (PTH/PTHLH type-3 receptor, and SOX9 (Sry-related high mobility group box in phalange, tibia and femur. Our results indicate that the only significant effect was a difference among bones for COL2A1 (femur > phalange. Therefore, we conclude that access to a perch did not alter transcript expression. Furthermore, because hens have been used as a model for human bone metabolism and osteoporosis, the results indicate that bone remodeling due to mechanical loading in chickens may be a product of different pathways than those involved in the mammalian model.

  19. Glutamate, Ornithine, Arginine, Proline, and Polyamine Metabolic Interactions: The Pathway Is Regulated at the Post-Transcriptional Level

    Science.gov (United States)

    Majumdar, Rajtilak; Barchi, Boubker; Turlapati, Swathi A.; Gagne, Maegan; Minocha, Rakesh; Long, Stephanie; Minocha, Subhash C.

    2016-01-01

    The metabolism of glutamate into ornithine, arginine, proline, and polyamines is a major network of nitrogen-metabolizing pathways in plants, which also produces intermediates like nitric oxide, and γ-aminobutyric acid (GABA) that play critical roles in plant development and stress. While the accumulations of intermediates and the products of this network depend primarily on nitrogen assimilation, the overall regulation of the interacting sub-pathways is not well understood. We tested the hypothesis that diversion of ornithine into polyamine biosynthesis (by transgenic approach) not only plays a role in regulating its own biosynthesis from glutamate but also affects arginine and proline biosynthesis. Using two high putrescine producing lines of Arabidopsis thaliana (containing a transgenic mouse ornithine decarboxylase gene), we studied the: (1) effects of exogenous supply of carbon and nitrogen on polyamines and pools of soluble amino acids; and, (2) expression of genes encoding key enzymes in the interactive pathways of arginine, proline and GABA biosynthesis as well as the catabolism of polyamines. Our findings suggest that: (1) the overall conversion of glutamate to arginine and polyamines is enhanced by increased utilization of ornithine for polyamine biosynthesis by the transgene product; (2) proline and arginine biosynthesis are regulated independently of polyamines and GABA biosynthesis; (3) the expression of most genes (28 that were studied) that encode enzymes of the interacting sub-pathways of arginine and GABA biosynthesis does not change even though overall biosynthesis of Orn from glutamate is increased several fold; and (4) increased polyamine biosynthesis results in increased assimilation of both nitrogen and carbon by the cells. PMID:26909083

  20. Anticancer properties of distinct antimalarial drug classes.

    Directory of Open Access Journals (Sweden)

    Rob Hooft van Huijsduijnen

    Full Text Available We have tested five distinct classes of established and experimental antimalarial drugs for their anticancer potential, using a panel of 91 human cancer lines. Three classes of drugs: artemisinins, synthetic peroxides and DHFR (dihydrofolate reductase inhibitors effected potent inhibition of proliferation with IC50s in the nM- low µM range, whereas a DHODH (dihydroorotate dehydrogenase and a putative kinase inhibitor displayed no activity. Furthermore, significant synergies were identified with erlotinib, imatinib, cisplatin, dasatinib and vincristine. Cluster analysis of the antimalarials based on their differential inhibition of the various cancer lines clearly segregated the synthetic peroxides OZ277 and OZ439 from the artemisinin cluster that included artesunate, dihydroartemisinin and artemisone, and from the DHFR inhibitors pyrimethamine and P218 (a parasite DHFR inhibitor, emphasizing their shared mode of action. In order to further understand the basis of the selectivity of these compounds against different cancers, microarray-based gene expression data for 85 of the used cell lines were generated. For each compound, distinct sets of genes were identified whose expression significantly correlated with compound sensitivity. Several of the antimalarials tested in this study have well-established and excellent safety profiles with a plasma exposure, when conservatively used in malaria, that is well above the IC50s that we identified in this study. Given their unique mode of action and potential for unique synergies with established anticancer drugs, our results provide a strong basis to further explore the potential application of these compounds in cancer in pre-clinical or and clinical settings.

  1. Selenoprotein Transcript Level and Enzyme Activity as Biomarkers for Selenium Status and Selenium Requirements of Chickens (Gallus gallus)

    Science.gov (United States)

    Li, Jin-Long; Sunde, Roger A.

    2016-01-01

    The NRC selenium (Se) requirement for broiler chicks is 0.15 μg Se/g diet, based primarily on weight gain and feed intake studies reported in 1986. To determine Se requirements in today’s rapidly growing broiler chick, day-old male chicks were fed Se-deficient basal diets supplemented with graded levels of Se (0, 0.025, 0.05, 0.075, 0.1, 0.2, 0.3, 0.5, 0.75, and 1.0 μg Se/g) as Na2SeO3 (5/treatment). Diets contained 15X the vitamin E requirement, and there were no gross signs of Se-deficiency. At 29 d, Se-deficient chicks weighed 62% of Se-supplemented chicks; 0.025 μg Se/g reversed this effect, indicating a minimum Se requirement of 0.025 μg Se/g diet for growth for male broiler chicks. Enzyme activities in Se-deficient chicks for plasma GPX3, liver and gizzard GPX1, and liver and gizzard GPX4 decreased dramatically to 3, 2, 5, 10 and 5%, respectively, of Se-adequate levels, with minimum Se requirements of 0.10–0.13 μg Se/g, and with defined plateaus above these levels. Pancreas GPX1 and GPX4 activities, however, lacked defined plateaus, with breakpoints at 0.3 μg Se/g. qPCR measurement of all 24 chicken selenoprotein transcripts, plus SEPHS1, found that SEPP1 in liver, GPX3 in gizzard, and SEPP1, GPX3 and SELK in pancreas were expressed at levels comparable to housekeeping transcripts. Only 33%, 25% and 50% of selenoprotein transcripts were down-regulated significantly by Se deficiency in liver, gizzard and pancreas, respectively. No transcripts could be used as biomarkers for supernutritional Se status. For export selenoproteins SEPP1 and GPX3, tissue distribution, high expression and Se-regulation clearly indicate unique Se metabolism, which may underlie tissues targeted by Se deficiency. Based on enzyme activities in liver, gizzard, and plasma, the minimum Se requirement in today’s broiler chick is 0.15 μg Se/g diet; pancreas data indicate that the Se requirement should be raised to 0.2 μg Se/g diet to provide a margin of safety. PMID:27045754

  2. Selenoprotein Transcript Level and Enzyme Activity as Biomarkers for Selenium Status and Selenium Requirements of Chickens (Gallus gallus).

    Science.gov (United States)

    Li, Jin-Long; Sunde, Roger A

    2016-01-01

    The NRC selenium (Se) requirement for broiler chicks is 0.15 μg Se/g diet, based primarily on weight gain and feed intake studies reported in 1986. To determine Se requirements in today's rapidly growing broiler chick, day-old male chicks were fed Se-deficient basal diets supplemented with graded levels of Se (0, 0.025, 0.05, 0.075, 0.1, 0.2, 0.3, 0.5, 0.75, and 1.0 μg Se/g) as Na2SeO3 (5/treatment). Diets contained 15X the vitamin E requirement, and there were no gross signs of Se-deficiency. At 29 d, Se-deficient chicks weighed 62% of Se-supplemented chicks; 0.025 μg Se/g reversed this effect, indicating a minimum Se requirement of 0.025 μg Se/g diet for growth for male broiler chicks. Enzyme activities in Se-deficient chicks for plasma GPX3, liver and gizzard GPX1, and liver and gizzard GPX4 decreased dramatically to 3, 2, 5, 10 and 5%, respectively, of Se-adequate levels, with minimum Se requirements of 0.10-0.13 μg Se/g, and with defined plateaus above these levels. Pancreas GPX1 and GPX4 activities, however, lacked defined plateaus, with breakpoints at 0.3 μg Se/g. qPCR measurement of all 24 chicken selenoprotein transcripts, plus SEPHS1, found that SEPP1 in liver, GPX3 in gizzard, and SEPP1, GPX3 and SELK in pancreas were expressed at levels comparable to housekeeping transcripts. Only 33%, 25% and 50% of selenoprotein transcripts were down-regulated significantly by Se deficiency in liver, gizzard and pancreas, respectively. No transcripts could be used as biomarkers for supernutritional Se status. For export selenoproteins SEPP1 and GPX3, tissue distribution, high expression and Se-regulation clearly indicate unique Se metabolism, which may underlie tissues targeted by Se deficiency. Based on enzyme activities in liver, gizzard, and plasma, the minimum Se requirement in today's broiler chick is 0.15 μg Se/g diet; pancreas data indicate that the Se requirement should be raised to 0.2 μg Se/g diet to provide a margin of safety. PMID:27045754

  3. In vivo Anticancer Activities of Benzophenone Semicarbazone against Ehrlich Ascites Carcinoma Cells in Swiss Albino Mice

    International Nuclear Information System (INIS)

    Benzophenone semicarbazone (BSC) was synthesized and characterized to identify compounds with anticancer activities. Anticancer activities were studied against Ehrlich Ascites Carcinoma (EAC) cells in Swiss albino mice by monitoring parameters such as tumor weight measurement, survival time of tumor bearing mice, tumor cell growth inhibition, and so on. Some hematological parameters, such as red blood cells, white blood cells, and hemoglobin content, were also measured. The results showed that BSC has a positive effect against EAC cells. An assessment was conducted by comparing these results with those obtained using the standard drug bleomycin. The BSC compound can be considered as a potent anticancer agent

  4. Anti-cancer Lead Molecule

    KAUST Repository

    Sagar, Sunil

    2014-04-17

    Derivatives of plumbagin can be selectively cytotoxic to breast cancer cells. Derivative `A` (Acetyl Plumbagin) has emerged as a lead molecule for testing against estrogen positive breast cancer and has shown low hepatotoxicity as well as overall lower toxicity in nude mice model. The toxicity of derivative `A` was determined to be even lower than vehicle control (ALT and AST markers). The possible mechanism of action identified based on the microarray experiments and pathway mapping shows that derivative `A` could be acting by altering the cholesterol-related mechanisms. The low toxicity profile of derivative `A` highlights its possible role\\'as future anti-cancer drug and/or as an adjuvant drug to reduce the toxicity of highly toxic chemotherapeutic\\'drugs

  5. Survivin knockdown increased anti-cancer effects of (−)-epigallocatechin-3-gallate in human malignant neuroblastoma SK-N-BE2 and SH-SY5Y cells

    International Nuclear Information System (INIS)

    network formation ability of cells was significantly inhibited by survivin silencing and completely by combination of survivin silencing and EGCG treatment. Collectively, survivin silencing potentiated anti-cancer effects of EGCG in human malignant neuroblastoma cells having survivin overexpression. -- Highlights: ► Survivin shRNA + EGCG controlled growth of human malignant neuroblastoma cells. ► Survivin knockdown induced neuronal differentiation in neuroblastoma cells. ► Survivin shRNA + EGCG induced morphological and biochemical features of apoptosis. ► Combination therapy inhibited invasion, proliferation, and angiogenesis as well. ► So, combination therapy showed multiple anti-cancer mechanisms in neuroblastoma.

  6. Influence of platelet-activating factor, lyso-platelet-activating factor and edelfosine on Langmuir monolayers imitating plasma membranes of cell lines differing in susceptibility to anti-cancer treatment: the effect of plasmalogen level

    OpenAIRE

    Flasiński, Michał; Hąc-Wydro, Katarzyna; Wydro, Paweł; Dynarowicz-Łątka, Patrycja

    2014-01-01

    Three structurally related but differing in biological activities single-chained ether phospholipids (PAF (platelet-activating factor) and lyso-PAF) and an anti-cancer drug (edelfosine (ED)) were investigated in Langmuir monolayers imitating natural membranes. The aim of the undertaken experiments was to study the influence of these lipids on monolayers mimicking plasma membranes of cell lines differing in susceptibility to the anti-cancer activity of ED, i.e. promyelocytic leukaemia cells (H...

  7. Theobroma cacao: Review of the Extraction, Isolation, and Bioassay of Its Potential Anti-cancer Compounds.

    Science.gov (United States)

    Baharum, Zainal; Akim, Abdah Md; Hin, Taufiq Yap Yun; Hamid, Roslida Abdul; Kasran, Rosmin

    2016-02-01

    Plants have been a good source of therapeutic agents for thousands of years; an impressive number of modern drugs used for treating human diseases are derived from natural sources. The Theobroma cacao tree, or cocoa, has recently garnered increasing attention and become the subject of research due to its antioxidant properties, which are related to potential anti-cancer effects. In the past few years, identifying and developing active compounds or extracts from the cocoa bean that might exert anti-cancer effects have become an important area of health- and biomedicine-related research. This review provides an updated overview of T. cacao in terms of its potential anti-cancer compounds and their extraction, in vitro bioassay, purification, and identification. This article also discusses the advantages and disadvantages of the techniques described and reviews the processes for future perspectives of analytical methods from the viewpoint of anti-cancer compound discovery. PMID:27019680

  8. Anticancer drug-induced kidney disorders.

    Science.gov (United States)

    Kintzel, P E

    2001-01-01

    Nephrotoxicity is an inherent adverse effect of certain anticancer drugs. Renal dysfunction can be categorised as prerenal uraemia, intrinsic damage or postrenal uraemia according to the underlying pathophysiological process. Renal hypoperfusion promulgates prerenal uraemia. Intrinsic renal damage results from prolonged hypoperfusion, exposure to exogenous or endogenous nephrotoxins, renotubular precipitation of xenobiotics or endogenous compounds, renovascular obstruction, glomerular disease, renal microvascular damage or disease, and tubulointerstitial damage or disease. Postrenal uraemia is a consequence of clinically significant urinary tract obstruction. Clinical signs of nephrotoxicity and methods used to assess renal function are discussed. Mechanisms of chemotherapy-induced renal dysfunction generally include damage to vasculature or structures of the kidneys, haemolytic uraemic syndrome and prerenal perfusion deficits. Patients with cancer are frequently at risk of renal impairment secondary to disease-related and iatrogenic causes. This article reviews the incidence, presentation, prevention and management of anticancer drug-induced renal dysfunction. Dose-related nephrotoxicity subsequent to administration of certain chloroethylnitrosourea compounds (carmustine, semustine and streptozocin) is commonly heralded by increased serum creatinine levels, uraemia and proteinuria. Additional signs of streptozocin-induced nephrotoxicity include hypophosphataemia, hypokalaemia, hypouricaemia, renal tubular acidosis, glucosuria, aceturia and aminoaciduria. Cisplatin and carboplatin cause dose-related renal dysfunction. In addition to increased serum creatinine levels and uraemia, electrolyte abnormalities, such as hypomagnesaemia and hypokalaemia, are commonly reported adverse effects. Rarely, cisplatin has been implicated as the underlying cause of haemolytic uraemic syndrome. Pharmaceutical antidotes to cisplatin-induced nephrotoxicity include amifostine, sodium

  9. Anticancer agent-based marine natural products and related compounds.

    Science.gov (United States)

    Chen, Jian-Wei; Wu, Qi-Hao; Rowley, David C; Al-Kareef, Ammar M Q; Wang, Hong

    2015-01-01

    Marine natural products constitute a huge reservoir of anticancer agents. Consequently during the past decades, several marine anticancer compounds have been isolated, identified, and approved for anticancer treatment or are under trials. In this article the sources, structure, bioactivities, mode of actions, and analogs of some promising marine and derived anticancer compounds have been discussed. PMID:25559315

  10. PEGylation in anti-cancer therapy: An overview

    OpenAIRE

    Prajna Mishra; Bismita Nayak; R. K. Dey

    2016-01-01

    Advanced drug delivery systems using poly(ethylene glycol) (PEG) is an important development in anti-cancer therapy. PEGylation has the ability to enhance the retention time of the therapeutics like proteins, enzymes small molecular drugs, liposomes and nanoparticles by protecting them against various degrading mechanisms active inside a tissue or cell, which consequently improves their therapeutic potential. PEGylation effectively alters the pharmacokinetics (PK) of a variety of drugs and dr...

  11. MEDICINAL PLANTS WITH POTENTIAL ANTICANCER ACTIVITIES: A REVIEW

    OpenAIRE

    Narah Merina; Kalita Jogen Chandra; Kotoky Jibon

    2012-01-01

    Plants have been the beacon of therapeutic sources for curing diseases from times immemorial. Medicinal plants with their isolated lead molecules are also used as an alternative medicine for treating neoplastic cells. Neoplastic cells are the anomalous proliferation of cells in the body which cause cancer. Diverse efficient compounds derived from natural products have been isolated as anticancer agents. These chemical compounds are formulated with a view to create effective drugs against can...

  12. Simultaneous Treatment of Cancer Cells Lines with the Anticancer Drug Cisplatin and the Antioxidant Fucoxanthin

    OpenAIRE

    Takeshi Mised; Takeshi Yasumoto

    2011-01-01

    The anti-oxidative properties and the other health benefits of fucoxanthin (Fx) make it a good candidate for a health food supplement. However, the use of antioxidant supplements in patients undergoing chemotherapy has been widely debated because of concerns that the antioxidants may interfere with the mechanisms of the anticancer drugs. To investigate this concern, we studied the effect of Fx on the anticancer drug cisplatin. Fucoxanthinol (Fxol), which is a deacetylated product produced dur...

  13. Anti-cancer activities of Ganoderma lucidum: active ingredients and pathways

    OpenAIRE

    Chi H.J. Kao; Jesuthasan, Amalini C; Karen S. Bishop; Marcus P. Glucina; Ferguson, Lynnette R

    2013-01-01

    ABSTRACTGanoderma lucidum, commonly referred to as Lingzhi, has been used in Asia for health promotion for centuries. The anti-cancer effects of G. lucidum have been demonstrated in both in vitro and in vivo studies. In addition, the observed anti-cancer activities of Ganoderma have prompted its usage by cancer patients alongside chemotherapy.The main two bioactive components of G. lucidum can be broadly grouped into triterpenes and polysaccharides. Despite triterpenes and polysaccharides bei...

  14. Novel anticancer agents from plant sources

    Institute of Scientific and Technical Information of China (English)

    Shah Unnati; Shah Ripal; Acharya Sanjeev; Acharya Niyati

    2013-01-01

    Plants remain an important source of new drugs,new drug leads and new chemical entities.Plant based drug discovery resulted mainly in the development of anticancer and anti-infectious agents,and continues to contribute to the new leads in clinical trials.Natural product drugs play a dominant role in pharmaceutical care.Several plant-derived compounds are currently successfully employed in cancer treatment.There are many classes of plant-derived cytotoxic natural products studied for further improvement and development of drugs.New anticancer drugs derived from research on plant antitumor agents will be continuously discovered.The basic aim of this review is to explore the potential of newly discovered anticancer compounds from medicinal plants,as a lead for anticancer drug development.It will be helpful to explore the medicinal value of plants and for new drug discovery from them for the researchers and scientists around the globe.

  15. Anticancer activity of Arkeshwara Rasa - A herbo-metallic preparation

    Science.gov (United States)

    Nafiujjaman, Md; Nurunnabi, Md; Saha, Samir Kumar; Jahan, Rownak; Lee, Yong-kyu; Rahmatullah, Mohammed

    2015-01-01

    Introduction: Though metal based drugs have been prescribed in Ayurveda for centuries to treat various diseases, such as rheumatoid arthritis and cancer, toxicity of these drugs containing heavy metal is a great drawback for practical application. So, proper scientific validation of herbo-metallic drugs like Arkeshwara Rasa (AR) have become one of the focused research arena of new drugs against cancers. Aim: To investigate the in vitro anticancer effects of AR. Materials and Methods: Anticancer activity of AR was investigated on two human cancer cell lines, which represent two different tissues (pancreas and skin). Lactate dehydrogenase (LDH) assay for enzyme activity and trypan blue assay for cell morphology were performed for further confirmation. Results: AR showed potent activity against pancreatic cancer cells (MIA-PaCa-2). LDH activity confirmed that AR was active against pancreatic cancer cells. Finally, it was observed that AR exhibited significant effects on cancer cells due to synergistic effects of different compounds of AR. Conclusion: The study strongly suggests that AR has the potential to be an anticancer drug against pancreatic cancer.

  16. Novel Marine Compounds: Anticancer or Genotoxic?

    OpenAIRE

    Arif, Jamal M.; Al-Hazzani, Amal A.; Muhammed Kunhi; Fahad Al-Khodairy

    2004-01-01

    In the past several decades, marine organisms have generously gifted to the pharmaceutical industries numerous naturally bioactive compounds with antiviral, antibacterial, antimalarial, anti-inflammatory, antioxidant, and anticancer potentials. But till date only few anticancer drugs (cytarabine, vidarabine) have been commercially developed from marine compounds while several others are currently in different clinical trials. Majority of these compounds were tested in the tumor xenograft mode...

  17. Indigofera suffruticosa: An Alternative Anticancer Therapy

    Directory of Open Access Journals (Sweden)

    Jeymesson Raphael Cardoso Vieira

    2007-01-01

    Full Text Available Indigofera suffruticosa Mill (Fabeceae occurs in the Northeast countryside and has intensive popular use in the treatment of infectious, inflammatory and other processes. The main aim of the present work was to investigate the cytotoxic and antitumor effects of aqueous extracts of leaves of I. suffruticosa obtained by infusion and maceration as well as to evaluate the toxicological properties. Aqueous extracts did not exhibit cytotoxicity against HEp-2 (human epidermoid cancer cell cell lines by MTT method. From the aqueous extract by infusion, the toxicological assay showed low order of toxicity. The antitumor effect of aqueous extracts by infusion (64.53% and maceration (62.62% against sarcoma 180 in mice at a dose of 50 mg kg−1 (intraperitoneally, based on low order of toxicity was comparable to the control group, which showed 100% development. Considering the low order of toxicity and that it is highly effective in inhibiting growth of solid tumors, the aqueous extracts of leaves of I. suffruticosa may be used as an alternative anticancer agent.

  18. In vitro and in vivo Methods for Anticancer Activity Evaluation and Some Indian Medicinal Plants Possessing Anticancer Properties: An Overview

    OpenAIRE

    Sumitra Chanda; Krunal Nagani

    2013-01-01

    Cancer is a major public health burden in both developed and developing countries. Anticancer activity is the effect of natural and synthetic or biological and chemical agents to reverse, suppress or prevent carcinogenic progression. Several synthetic agents are used to cure the disease but they have their toxicity and hence the research is going on to investigate the plant derived chemotherapeutic agents. Therefore an attempt has been made to review different in vitro and in vivo methods for...

  19. Potential Anti-Cancer Activities and Mechanisms of Costunolide and Dehydrocostuslactone

    Directory of Open Access Journals (Sweden)

    Xuejing Lin

    2015-05-01

    Full Text Available Costunolide (CE and dehydrocostuslactone (DE are derived from many species of medicinal plants, such as Saussurea lappa Decne and Laurus nobilis L. They have been reported for their wide spectrum of biological effects, including anti-inflammatory, anticancer, antiviral, antimicrobial, antifungal, antioxidant, antidiabetic, antiulcer, and anthelmintic activities. In recent years, they have caused extensive interest in researchers due to their potential anti-cancer activities for various types of cancer, and their anti-cancer mechanisms, including causing cell cycle arrest, inducing apoptosis and differentiation, promoting the aggregation of microtubule protein, inhibiting the activity of telomerase, inhibiting metastasis and invasion, reversing multidrug resistance, restraining angiogenesis has been studied. This review will summarize anti-cancer activities and associated molecular mechanisms of these two compounds for the purpose of promoting their research and application.

  20. An ensemble-guided approach identifies ClpP as a major regulator of transcript levels in nitric oxide-stressed Escherichia coli.

    Science.gov (United States)

    Robinson, Jonathan L; Brynildsen, Mark P

    2015-09-01

    The importance of NO(∙) to immunity is highlighted by the diversity of pathogens that require NO(∙)-defensive systems to establish infections. Proteases have been identified to aid pathogens in surviving macrophage attack, inspiring us to investigate their role during NO(∙) stress in Escherichia coli. We discovered that the elimination of ClpP largely impaired NO(∙) detoxification by E. coli. Using a quantitative model of NO(∙) stress, we employed an ensemble-guided approach to identify the underlying mechanism. Iterations of in silico analyses and corresponding experiments identified the defect to result from deficient transcript levels of hmp, which encodes NO(∙) dioxygenase. Interestingly, the defect was not confined to hmp, as ΔclpP imparted widespread perturbations to the expression of NO(∙)-responsive genes. This work identified a target for anti-infective therapies based on disabling NO(∙) defenses, and demonstrated the utility of model-based approaches for exploring the complex, systems-level stress exerted by NO(∙). PMID:26112956

  1. ICE1 of Pyrus ussuriensis functions in cold tolerance by enhancing PuDREBa transcriptional levels through interacting with PuHHP1

    Science.gov (United States)

    Huang, Xiaosan; Li, Kongqing; Jin, Cong; Zhang, Shaoling

    2015-12-01

    ICE1 transcription factor plays an important role in plant cold stress via regulating the expression of stress-responsive genes. In this study, a PuICE1 gene isolated from Pyrus ussuriensis was characterized for its function in cold tolerance. The expression levels of the PuICE1 were induced by cold, dehydration and salt, with the greatest induction under cold conditions. PuICE1 was localized in the nucleus and could bind specifically to the MYC element in the PuDREBa promoter. The PuICE1 fused to the GAL4 DNA-binding domain to have transcriptional activation activity. Ectopic expression of the PuICE1 in tomato conferred enhanced tolerance to cold stress at cold temperatures, less electrolyte leakage, less MDA content, higher chlorophyll content, higher survival rate, higher proline content, higher activities of enzymes. In additon, steady-state mRNA levels of six stress-responsive genes coding for either functional or regulatory genes were induced to higher levels in the transgenic lines by cold stress. Yeast two-hybrid, transient assay, split luciferase complementation and BiFC assays all revealed that PuHHP1 protein can physically interact with PuICE1. Taken together, these results demonstrated that PuICE1 plays a positive role in cold tolerance, which may be due to enhancement of PuDREBa transcriptional levels through interacting with the PuHHP1.

  2. Cold acclimation induces distinctive changes in the chromatin state and transcript levels of COR genes in Cannabis sativa varieties with contrasting cold acclimation capacities.

    Science.gov (United States)

    Mayer, Boris F; Ali-Benali, Mohamed Ali; Demone, Jordan; Bertrand, Annick; Charron, Jean-Benoit

    2015-11-01

    Little is known about the capacity of Cannabis sativa to cold-acclimate and develop freezing tolerance. This study investigates the cold acclimation (CA) capacity of nine C. sativa varieties and the underlying genetic and epigenetic responses. The varieties were divided into three groups based on their contrasting CA capacities by comparing the survival of non-acclimated and cold-acclimated plants in whole-plant freeze tests. In response to the CA treatment, all varieties accumulated soluble sugars but only the varieties with superior capacity for CA could maintain higher levels throughout the treatment. In addition, the varieties that acclimated most efficiently accumulated higher transcript levels of cold-regulated (COR) genes and genes involved in de novo DNA methylation while displaying locus- and variety-specific changes in the levels of H3K9ac, H3K27me3 and methylcytosine (MeC) during CA. Furthermore, these hardy C. sativa varieties displayed significant increases in MeC levels at COR gene loci when deacclimated, suggesting a role for locus-specific DNA methylation in deacclimation. This study uncovers the molecular mechanisms underlying CA in C. sativa and reveals higher levels of complexity regarding how genetic, epigenetic and environmental factors intertwine. PMID:25534661

  3. Potential role of garcinol as an anticancer agent.

    Science.gov (United States)

    Saadat, Nadia; Gupta, Smiti V

    2012-01-01

    Garcinol, a polyisoprenylated benzophenone, is extracted from the rind of the fruit of Garcinia indica, a plant found extensively in tropical regions. Although the fruit has been consumed traditionally over centuries, its biological activities, specifically its anticancer potential is a result of recent scientific investigations. The anticarcinogenic properties of garcinol appear to be moderated via its antioxidative, anti-inflammatory, antiangiogenic, and proapoptotic activities. In addition, garcinol displays effective epigenetic influence by inhibiting histone acetyltransferases (HAT 300) and by possible posttranscriptional modulation by mi RNA profiles involved in carcinogenesis. In vitro as well as some in vivo studies have shown the potential of this compound against several cancers types including breast, colon, pancreatic, and leukemia. Although this is a promising molecule in terms of its anticancer properties, investigations in relevant animal models, and subsequent human trials are warranted in order to fully appreciate and confirm its chemopreventative and/or therapeutic potential. PMID:22745638

  4. Anti-cancer activities of diospyrin, its derivatives and analogues

    KAUST Repository

    Sagar, Sunil

    2010-09-01

    Natural products have played a vital role in drug discovery and development process for cancer. Diospyrin, a plant based bisnaphthoquinonoid, has been used as a lead molecule in an effort to develop anti-cancer drugs. Several derivatives/analogues have been synthesized and screened for their pro-apoptotic/anti-cancer activities so far. Our review is focused on the pro-apoptotic/anti-cancer activities of diospyrin, its derivatives/analogues and the different mechanisms potentially involved in the bioactivity of these compounds. Particular focus has been placed on the different mechanisms (both chemical and molecular) thought to underlie the bioactivity of these compounds. A brief bioinformatics analysis at the end of the article provides novel insights into the new potential mechanisms and pathways by which these compounds might exert their effects and lead to a better realization of the full therapeutic potential of these compounds as anti-cancer drugs. © 2010 Elsevier Masson SAS. All rights reserved.

  5. Potential Anti-cancer Activity of Furanodiene

    Institute of Scientific and Technical Information of China (English)

    Zhen-zhen Ba; Yan-ping Zheng; Hui Zhang; Xiu-yan Sun; Dong-hai Lin

    2009-01-01

    Objective: To study the anti-tumor activities of furanodiene (C15H20O), a primary sesquiterpene compound isolated from the essential oil of the rhizome of Curcuma wenyujin YH Chen et C. Ling(Wen Ezhu), in vitro and in vivo.Methods: In vitro MTT assay was used to further study the effects of time and dosage on anti-proliferation of furanodiene against the sensitive Hela, Hep-2,HL-60, U251 cells, based on the cytotoxic effects of furanodiene on 12 human malignant tumor cell lines with the essential oil of Wen Ezhu as control., and the half-inhibitory concentration (IC50) was observed. In vivo uterine cervix (U14) tumor cell was selected and the conventional assay method of anti-tumor activity was employed. Furanodiene liposome was administered intraperitoneally, and tumor-inhibitory rate, thymus and spleen indexes were observed.Results: The inhibitive effects on cell proliferation were shown in all of the twelve cell lines and the cytotoxic effects of furanodiene against Hela, Hep-2, HL-60, U251 cells were observed after 12 h of administration, the effect could last for at least 48 h in a dose dependent manner, and the IC50 values were 0.6, 1.7, 1.8, 7.0 μg/ml, respectively. Furanodiene was also found to show inhibitive effects on the proliferation of uterine cervix (U14) tumor induced in mice. The tumor inhibition rates were 36.09% (40 mg/kg), 41.55% (60 mg/kg), 58.29% (80 mg/kg), respectively.Conclusion: Furanodiene is one of primary anti-cancer active components in the essential oil of Wen Ezhu, and also a very effective agent against uterine cervix cancer, and has protection effect on the immune function.

  6. Calcium carbonate microspheres as carriers for the anticancer drug camptothecin

    Energy Technology Data Exchange (ETDEWEB)

    Qiu, Neng [Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow, G12 8LT (United Kingdom); State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Department of Bio-pharmaceutical Engineering, School of Chemical Engineering, Sichuan University, Chengdu ,610065 (China); Yin, Huabing, E-mail: huabing.yin@glasgow.ac.uk [Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow, G12 8LT (United Kingdom); Ji, Bozhi; Klauke, Norbert; Glidle, Andrew [Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow, G12 8LT (United Kingdom); Zhang, Yongkui; Song, Hang [Department of Bio-pharmaceutical Engineering, School of Chemical Engineering, Sichuan University, Chengdu ,610065 (China); Cai, Lulu; Ma, Liang; Wang, Guangcheng [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Chen, Lijuan, E-mail: lijuan17@hotmail.com [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Wang, Wenwen [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China)

    2012-12-01

    Biogenic calcium carbonate has come to the attention of many researchers as a promising drug delivery system due to its safety, pH sensitivity and the large volume of information already in existence on its medical use. In this study, we employed bovine serum albumin (BSA) as an additive to synthesize a series of porous calcium carbonate microspheres (CCMS). These spheres, identified as vaterite, are stable both in aqueous solutions and organic solvents. Camptothecin, an effective anticancer agent, was loaded into the CCMS by simple diffusion and adsorption. The camptothecin loaded CCMS showed sustained cell growth inhibitory activity and a pH dependent release of camptothecin. With a few hours, the release is negligible under physiological conditions (pH = 7.4) but almost complete at pH 4 to 6 (i.e. pHs found in lysosomes and solid tumor tissue respectively). These findings suggest that porous, biogenic calcium carbonate microspheres could be promising carriers for the safe and efficient delivery of anticancer drugs of low aqueous solubility. - Highlights: Black-Right-Pointing-Pointer BSA-doped calcium carbonate microspheres with porous structure were prepared. Black-Right-Pointing-Pointer Camptothecin was encapsulated in the spherical microparticles with encapsulation efficiency up to 11%. Black-Right-Pointing-Pointer The release of encapsulated camptothecin is pH dependent Black-Right-Pointing-Pointer In vitro studies showed an effective anticancer activity of the camptothecin- microspheres.

  7. Anti-cancer activity of compounds from Cassia garrettiana heartwood

    Directory of Open Access Journals (Sweden)

    Supreeya Yuenyongsawad

    2014-04-01

    Full Text Available The ethanol extract of Cassia garrettiana heartwood showed marked inhibitory activity against several cancer cell lines including HT-29, HeLa, MCF-7 and KB cells. Therefore, its extract and compounds were investigated for their anticancer effect using the Sulforhodamine B (SRB assay. The ethanol extract of C. garrettiana heartwood was separated to give five compounds which are chrysophanol (1, piceatannol (2, aloe-emodin (3, emodin (4 and cassigarol E (5. Of the tested samples, chrysophanol (1 showed the highest anti-cancer activity against KB cells (IC50 = 0.045 g/mL, aloe emodin (3 was the most active against HT-29 (IC50 = 0.29 g/mL, emodin (4 was against HeLa cells (IC50 = 0.82 g/mL, and cassigarol E (5 was active against MCF-7 (IC50 = 0.021 g/mL, whereas piceatannol (2 was inactive in all tested cell lines. This is the first report of anti-cancer effect against HT-29, HeLa, MCF-7 and KB cells of C. garrettiana heartwood.

  8. Calcium carbonate microspheres as carriers for the anticancer drug camptothecin

    International Nuclear Information System (INIS)

    Biogenic calcium carbonate has come to the attention of many researchers as a promising drug delivery system due to its safety, pH sensitivity and the large volume of information already in existence on its medical use. In this study, we employed bovine serum albumin (BSA) as an additive to synthesize a series of porous calcium carbonate microspheres (CCMS). These spheres, identified as vaterite, are stable both in aqueous solutions and organic solvents. Camptothecin, an effective anticancer agent, was loaded into the CCMS by simple diffusion and adsorption. The camptothecin loaded CCMS showed sustained cell growth inhibitory activity and a pH dependent release of camptothecin. With a few hours, the release is negligible under physiological conditions (pH = 7.4) but almost complete at pH 4 to 6 (i.e. pHs found in lysosomes and solid tumor tissue respectively). These findings suggest that porous, biogenic calcium carbonate microspheres could be promising carriers for the safe and efficient delivery of anticancer drugs of low aqueous solubility. - Highlights: ► BSA-doped calcium carbonate microspheres with porous structure were prepared. ► Camptothecin was encapsulated in the spherical microparticles with encapsulation efficiency up to 11%. ► The release of encapsulated camptothecin is pH dependent ► In vitro studies showed an effective anticancer activity of the camptothecin- microspheres.

  9. Anticancer activity of flavane gallates isolated from Plicosepalus curviflorus

    Directory of Open Access Journals (Sweden)

    Ghada Ahmed Fawzy

    2014-01-01

    Full Text Available Background: Previous investigation of the methanol extract of Plicosepalus curviflorus leaves led to the isolation of two new flavane gallates (1, 2, together with other compounds including quercetin (3. The stems of P. curviflorus are used traditionally for the treatment of cancer in Yemen. Objective: The aim of this study was to evaluate the anticancer activity of the plant methanol extract as well as isolated compounds (1-3. Materials and Methods: The human cancer cell lines used were; MCF-7, HepG-2, HCT-116, Hep-2, HeLa and normal, Vero cell line using the Crystal Violet Staining method (CVS. Results: Quercetin (3 possessed the highest anticancer effect against all five cell lines (IC 50 ranging from 3.6 to 16.2 μg/ml. It was followed by 2S, 3R-3, 3′, 4′, 5, 7-pentahydroxyflavane-5-O-gallate (1 , with IC 50 ranging from 11.6 to 38.8 μg/ml. The weakest anticancer activity was given by 2S, 3R-3,3′,4′,5,5′,7-hexahydroxyflavane-3′,5-di-O-gallate (2 with IC 50 ranging from 39.8 to above 50 μg/ml, compared to vinblastine sulphate as reference drug. Colon, liver and breast cell lines seemed to be more sensitive to the tested compounds than the cervical and laryngeal cell lines. Concerning the cytotoxic effect on Vero cell line, the pentahydroxyflavane-5-O-gallate (1 showed the highest IC 50 ( 138.2 μg/ml, while quercetin exhibited the lowest IC 50 to Vero cells (30.5 μg/ml, compared to vinblastine sulphate as reference drug (IC 50: 39.7 μg/ml. Conclusion: The results suggest the possible use of compounds 1 and 3 as anticancer drugs especially against colon and liver cancers.

  10. Potential Anticancer Properties of Grape Antioxidants

    Directory of Open Access Journals (Sweden)

    Kequan Zhou

    2012-01-01

    Full Text Available Dietary intake of foods rich in antioxidant properties is suggested to be cancer protective. Foods rich in antioxidant properties include grape (Vitis vinifera, one of the world’s largest fruit crops and most commonly consumed fruits in the world. The composition and cancer-protective effects of major phenolic antioxidants in grape skin and seed extracts are discussed in this review. Grape skin and seed extracts exert strong free radical scavenging and chelating activities and inhibit lipid oxidation in various food and cell models in vitro. The use of grape antioxidants are promising against a broad range of cancer cells by targeting epidermal growth factor receptor (EGFR and its downstream pathways, inhibiting over-expression of COX-2 and prostaglandin E2 receptors, or modifying estrogen receptor pathways, resulting in cell cycle arrest and apoptosis. Interestingly, some of these activities were also demonstrated in animal models. However, in vivo studies have demonstrated inconsistent antioxidant efficacy. Nonetheless, a growing body of evidence from human clinical trials has demonstrated that consumption of grape, wine and grape juice exerts many health-promoting and possible anti-cancer effects. Thus, grape skin and seed extracts have great potential in cancer prevention and further investigation into this exciting field is warranted.

  11. Quercetin induces cell cycle arrest and apoptosis in CD133+ cancer stem cells of human colorectal HT29 cancer cell line and enhances anticancer effects of doxorubicin

    Directory of Open Access Journals (Sweden)

    Shekoufeh Atashpour

    2015-07-01

    Conclusion:The CSCs were a minor population with a significantly high level of drug resistance within the HT29 cancer cells. Quercetin alone exhibited significant cytotoxic effects on HT29 cells and also increased cytoxicity of Dox in combination therapy. Altogether, our data showed that adding quercetin to Dox chemotherapy is an effective strategy for treatment of both CSCs and bulk tumor cells.

  12. Delivering anti-cancer drugs with endosomal pH-sensitive anti-cancer liposomes.

    Science.gov (United States)

    Moku, Gopikrishna; Gulla, Suresh Kumar; Nimmu, Narendra Varma; Khalid, Sara; Chaudhuri, Arabinda

    2016-04-22

    Numerous prior studies have been reported on the use of pH-sensitive drug carriers such as micelles, liposomes, peptides, polymers, nanoparticles, etc. that are sensitive to the acidic (pH = ∼6.5) microenvironments of tumor tissues. Such systems have been primarily used in the past as effective drug/gene/microRNA carriers for releasing their anti-cancer payloads selectively to tumor cells/tissues. Herein, we report on the development of new liposomal drug carriers prepared from glutamic acid backbone-based cationic amphiphiles containing both endosomal pH-sensitive histidine as well as cellular uptake & solubility enhancing guanidine moieties in their polar head-group regions. The most efficient one among the four presently described endosomal pH-sensitive liposomal drug carriers not only effectively delivers potent anti-cancer drugs (curcumin & paclitaxel) to mouse tumor, but also significantly contributes to inhibiting mouse tumor growth. The findings in the in vitro mechanistic studies are consistent with apoptosis of tumor cells being mediated through increased cell cycle arrest in the G2/M phase. Findings in the FRET assay and in vitro drug release studies conducted with the liposomes of the most efficient pH-sensitive lipid demonstrated its pH dependent fusogenic and controlled curcumin release properties. Importantly, the presently described liposomal formulation of curcumin & paclitaxel enhanced overall survivability of tumor bearing mice. To the best of our knowledge, the presently described system (curcumin, paclitaxel and liposomal carrier itself) is the first of its kind pH-sensitive liposomal formulation of potent chemotherapeutics in which the liposomal drug itself exhibits significant mouse tumor growth inhibition properties. PMID:26806172

  13. Inhibitory effect of berberine on the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2

    International Nuclear Information System (INIS)

    Berberine, a compound isolated from medicinal herbs, has been reported with many pharmacological effects related to anti-cancer and anti-inflammation capabilities. In this study, we observed that berberine exerted a dose- and time-dependent inhibitory effect on the motility and invasion ability of a highly metastatic A549 cells under non-cytotoxic concentrations. In cancer cell migration and invasion process, matrix-degrading proteinases are required. A549 cell treated with berberine at various concentrations showed reduced ECM proteinases including matrix metalloproteinase-2 (MMP2) and urokinase-plasminogen activator (u-PA) by gelatin and casein zymography analysis. The inhibitory effect is likely to be at the transcriptional level, since the reduction in the transcripts levels was corresponding to the proteins. Moreover, berberine also exerted its action via regulating tissue inhibitor of metalloproteinase-2 (TIMP-2) and urokinase-plasminogen activator inhibitor (PAI). The upstream mediators of the effect involved c-jun, c-fos and NF-κB, as evidenced by reduced phosphorylation of the proteins. These findings suggest that berberine possesses an anti-metastatic effect in non-small lung cancer cell and may, therefore, be helpful in clinical treatment

  14. 长效和短效NO发生剂体内干预疟原虫红内期重要侵袭分子转录水平的观察%Transcription Levels of Important Invasive Molecules after Long-Acting and Short-Acting NO Donor to Interfere Plasmodium during Erythrocytic Stage in vivo

    Institute of Scientific and Technical Information of China (English)

    郑丽; 李银燕; 刘军; 潘艳艳; 李莹; 延娟; 曹雅明

    2011-01-01

    为探讨NO对疟原虫红内期侵袭相关分子MSP-1、AMA-1和RhopH complex转录水平的影响.通过雌性BALB/c小鼠腹腔感染1 ×106致死型约氏疟原虫P.yoelii 17XL,体内给予NO长效(NOC18)和短效( NOC5)发生剂进行干预后,纯化疟原虫成熟裂殖体,提取总RNA,通过Real-time PCR相对定量方法检测MSP-1、AMA-1和RhopH complex的转录水平.结果显示和正常感染组相比,NOC5处理后疟原虫侵入的关键分子MSP-1、AMA-1和RhopH complex的转录水平明显下降;而NOC18处理则未见这一现象.本研究结果提示NO抑制疟原虫侵袭关键分子的转录水平,进而可能下调疟原虫相应蛋白的表达,从而影响疟原虫的侵入过程.%The effects of NO on the transcription levels of correlated invasive molecules MSP-1, AMA-1, and RhopH complex during Plasmodium erythrocytic stage were investigated. Female BALB/c mice were infected with 1 x 106 lethal type Plasmodium yoelii 17XL in abdominal cavity, then the mice were treated with long-acting NO (NOC18) and short-acting NO ( N0C5 ) donors in vivo to cany out interference. Mature Plasmodium schizonts were purified and extracted their total RNA. The transcription levels of MSP-1, AMA-1, and RhopH complex were detected by real-time PCR relative quantitative determination. The results showed that the transcription levels of key molecules of MSP-1, AMA-1, and RhopH complex of Plasmodium invasion after treated with NOC5 decreased tangibly as compared with normal infected groups. However, the phenomenon was not seen in the groups treated with NOC18. These result indicated that NO inhibited the transcription levels of Plasmodium invasive key molecules, and proceeded to reduce the expression of Plasmodium corresponding protein, therefore, affected the Plasmodium invasive process.

  15. Multistimuli-Responsive Bilirubin Nanoparticles for Anticancer Therapy.

    Science.gov (United States)

    Lee, Yonghyun; Lee, Soyoung; Lee, Dong Yun; Yu, Byeongjun; Miao, Wenjun; Jon, Sangyong

    2016-08-26

    Although stimuli-responsive materials hold potential for use as drug-delivery carriers for treating cancers, their clinical translation has been limited. Ideally, materials used for the purpose should be biocompatible and nontoxic, provide "on-demand" drug release in response to internal or external stimuli, allow large-scale manufacturing, and exhibit intrinsic anticancer efficacy. We present multistimuli-responsive nanoparticles formed from bilirubin, a potent endogenous antioxidant that possesses intrinsic anticancer and anti-inflammatory activity. Exposure of the bilirubin nanoparticles (BRNPs) to either reactive oxygen species (ROS) or external laser light causes rapid disruption of the BRNP nanostructure as a result of a switch in bilirubin solubility, thereby releasing encapsulated drugs. In a xenograft tumor model, BRNPs loaded with the anticancer drug doxorubicin (DOX@BRNPs), when combined with laser irradiation of 650 nm, significantly inhibited tumor growth. This study suggests that BRNPs may be used as a drug-delivery carrier as well as a companion medicine for effectively treating cancers. PMID:27485478

  16. A survey on anticancer effects of artemisinin, iron, miconazole, and butyric acid on 5637 (bladder cancer and 4T1 (Breast cancer cell lines

    Directory of Open Access Journals (Sweden)

    Amir Ali Shahbazfar

    2014-01-01

    The groups treated with miconazole showed identical changes, with less severity compared to combination therapy groups. In butyric acid-treated groups, the only detectable changes were, mild cell swelling, few apoptosis, and rare necrosis. Conclusions: A combination therapy with artemisinin can be more effective against cancer cells than monotherapy with that. Butyric acid was not effective on cancer cells. Miconazole deviated the nature of cell death from apoptosis to necrosis and it must be used under caution.

  17. MECHANOMAGNETIC REACTOR FOR ACTIVATION OF ANTICANCER DRUGS

    Directory of Open Access Journals (Sweden)

    Orel V. E.

    2014-02-01

    Full Text Available Mechanomagnetochemical activation can increase the concentration of paramagnetic centers (free radicals in the anticancer drug, for example, doxorubicin that enables to influence its magnetic properties under external electromagnetic field and improve its magnetic sensitivity and antitumor activity. The principles of design and operation of mechanomagnetic reactor for implementation of this technology which includes mechanomagnetochemical activation and electromagnetic radiation of the drug are described in the paper. The methods of vibration magnetometry, electron paramagnetic resonance spectroscopy and high-performance liquid chromatography were used for studying of doxorubicin mechanomagnetic activation effects. The studies have shown that a generator of sinusoidal electromagnetic wave, working chambers from caprolactam, fluoroplastic or organic materials with metal inserts and working bodies made from steel or agate depending on the required doxorubicin magnetic properties are expedient to use in the designed mechanomagnic reactor. Under influence of mechanomagnetochemical activation doxorubicin, which is diamagnetic, acquires the properties of paramagnetic without changing g-factors in the spectra of electron paramagnetic resonance. Mechanomagnetochemical activation of doxorubicin satisfies pharmacopoeia condi tions according to the results of liquid chromatography that points on perspective of this method using in technology of tumor therapy with nanosized structures and external electromagnetic radiation.

  18. NSAIDs: Old Drugs Reveal New Anticancer Targets

    Directory of Open Access Journals (Sweden)

    Gary A. Piazza

    2010-05-01

    Full Text Available There is compelling evidence that nonsteroidal anti-inflammatory drugs (NSAIDs and cyclooxygenase-2 selective inhibitors have antineoplastic activity, but toxicity from cyclooxygenase (COX inhibition and the suppression of physiologically important prostaglandins limits their use for cancer chemoprevention. Previous studies as reviewed here suggest that the mechanism for their anticancer properties does not require COX inhibition, but instead involves an off-target effect. In support of this possibility, recent molecular modeling studies have shown that the NSAID sulindac can be chemically modified to selectively design out its COX-1 and COX-2 inhibitory activity. Unexpectedly, certain derivatives that were synthesized based on in silico modeling displayed increased potency to inhibit tumor cell growth. Other experiments have shown that sulindac can inhibit phosphodiesterase to increase intracellular cyclic GMP levels and that this activity is closely associated with its ability to selectively induce apoptosis of tumor cells. Together, these studies suggest that COX-independent mechanisms can be targeted to develop safer and more efficacious drugs for cancer chemoprevention.

  19. Changes in Air CO₂ Concentration Differentially Alter Transcript Levels of NtAQP1 and NtPIP2;1 Aquaporin Genes in Tobacco Leaves.

    Science.gov (United States)

    Secchi, Francesca; Schubert, Andrea; Lovisolo, Claudio

    2016-01-01

    The aquaporin specific control on water versus carbon pathways in leaves is pivotal in controlling gas exchange and leaf hydraulics. We investigated whether Nicotiana tabacum aquaporin 1 (NtAQP1) and Nicotiana tabacum plasma membrane intrinsic protein 2;1 (NtPIP2;1) gene expression varies in tobacco leaves subjected to treatments with different CO₂ concentrations (ranging from 0 to 800 ppm), inducing changes in photosynthesis, stomatal regulation and water evaporation from the leaf. Changes in air CO₂ concentration ([CO₂]) affected net photosynthesis (Pn) and leaf substomatal [CO₂] (Ci). Pn was slightly negative at 0 ppm air CO₂; it was one-third that of ambient controls at 200 ppm, and not different from controls at 800 ppm. Leaves fed with 800 ppm [CO₂] showed one-third reduced stomatal conductance (gs) and transpiration (E), and their gs was in turn slightly lower than in 200 ppm- and in 0 ppm-treated leaves. The 800 ppm air [CO₂] strongly impaired both NtAQP1 and NtPIP2;1 gene expression, whereas 0 ppm air [CO₂], a concentration below any in vivo possible conditions and specifically chosen to maximize the gene expression alteration, increased only the NtAQP1 transcript level. We propose that NtAQP1 expression, an aquaporin devoted to CO₂ transport, positively responds to CO₂ scarcity in the air in the whole range 0-800 ppm. On the contrary, expression of NtPIP2;1, an aquaporin not devoted to CO₂ transport, is related to water balance in the leaf, and changes in parallel with gs. These observations fit in a model where upregulation of leaf aquaporins is activated at low Ci, while downregulation occurs when high Ci saturates photosynthesis and causes stomatal closure. PMID:27089333

  20. Changes in Air CO2 Concentration Differentially Alter Transcript Levels of NtAQP1 and NtPIP2;1 Aquaporin Genes in Tobacco Leaves

    Science.gov (United States)

    Secchi, Francesca; Schubert, Andrea; Lovisolo, Claudio

    2016-01-01

    The aquaporin specific control on water versus carbon pathways in leaves is pivotal in controlling gas exchange and leaf hydraulics. We investigated whether Nicotiana tabacum aquaporin 1 (NtAQP1) and Nicotiana tabacum plasma membrane intrinsic protein 2;1 (NtPIP2;1) gene expression varies in tobacco leaves subjected to treatments with different CO2 concentrations (ranging from 0 to 800 ppm), inducing changes in photosynthesis, stomatal regulation and water evaporation from the leaf. Changes in air CO2 concentration ([CO2]) affected net photosynthesis (Pn) and leaf substomatal [CO2] (Ci). Pn was slightly negative at 0 ppm air CO2; it was one-third that of ambient controls at 200 ppm, and not different from controls at 800 ppm. Leaves fed with 800 ppm [CO2] showed one-third reduced stomatal conductance (gs) and transpiration (E), and their gs was in turn slightly lower than in 200 ppm– and in 0 ppm–treated leaves. The 800 ppm air [CO2] strongly impaired both NtAQP1 and NtPIP2;1 gene expression, whereas 0 ppm air [CO2], a concentration below any in vivo possible conditions and specifically chosen to maximize the gene expression alteration, increased only the NtAQP1 transcript level. We propose that NtAQP1 expression, an aquaporin devoted to CO2 transport, positively responds to CO2 scarcity in the air in the whole range 0–800 ppm. On the contrary, expression of NtPIP2;1, an aquaporin not devoted to CO2 transport, is related to water balance in the leaf, and changes in parallel with gs. These observations fit in a model where upregulation of leaf aquaporins is activated at low Ci, while downregulation occurs when high Ci saturates photosynthesis and causes stomatal closure. PMID:27089333

  1. Anti-cancer Effects of Novel Flavonoid Vicenin-2 as a Single Agent and in Synergistic Combination with Docetaxel in Prostate Cancer

    OpenAIRE

    Nagaprashantha, Lokesh Dalasanur; Vatsyayan, Rit; Singhal, Jyotsana; Fast, Spence; Roby, Rhonda; Awasthi, Sanjay; SINGHAL, SHARAD S.

    2011-01-01

    The present study was conducted to determine the efficacy of novel flavonoid vicenin-2 (VCN-2), an active constituent of the medicinal herb Ocimum Sanctum Linn or Tulsi, as a single agent and in combination with docetaxel (DTL) in carcinoma of prostate (CaP). VCN-2 effectively induced anti-proliferative, anti-angiogenic and pro-apoptotic effect in CaP cells (PC-3, DU-145 and LNCaP) irrespective of their androgen responsiveness or p53 status. VCN-2 inhibited EGFR/Akt/mTOR/ p70S6K pathway along...

  2. The Influence of Developmental Stage on the Relationship Between Severity of Late Effects of Anticancer Therapy and Perceived Quality of Life of Childhood Cancer Survivors

    Czech Academy of Sciences Publication Activity Database

    Blatný, Marek; Jelínek, Martin; Sobotková, Veronika; Kepák, T.

    2013-01-01

    Roč. 3, August (2013), s. 1-5. ISSN 2158-2440 R&D Projects: GA ČR(CZ) GAP407/11/2421 Institutional support: RVO:68081740 Keywords : childhood cancer survivors * quality of life * late effects * age differences Subject RIV: AN - Psychology http://sgo.sagepub.com/content/3/3/2158244013500678

  3. Connexin32‑mediated antitumor effects of suicide gene therapy against hepatocellular carcinoma: In vitro and in vivo anticancer activity.

    Science.gov (United States)

    Wu, Lun; Zhou, Wen-Bo; Shen, Feng; Liu, Wei; Wu, Hong-Wei; Zhou, Shi-Ji; Li, Sheng-Wei

    2016-04-01

    Normal hepatocytes express connexin32 (Cx32), which forms gap junctions at cell‑cell contact areas. The aim of the present study was to investigate whether Cx32 mediates the cell death‑inducing effects of ultrasound microbubbles carrying the herpes simplex virus thymidine kinase (HSV‑TK) suicide gene against hepatocellular carcinoma cells in vitro and in vivo. HepG2 cells were exposed to different concentrations of trans‑retinoic acid (ATRA) in culture, to evaluate the intrinsic antitumor effect of ATRA. Detailed in‑vitro and in‑vivo investigations on the antitumor effects of ATRA via Cx32 mediation were performed, and the possible underlying mechanisms of action of the compound were then examined. The gene expression of HSV‑TK transfected by ultrasound wave irradiation in the HepG2 cells was quantified using reverse transcription‑quantitative polymerase chain reaction analysis. The effects on cell death were assessed using an MTT assay. The protein expression levels of Cx32 in ATRA‑untreated or ATRA‑treated tissues were quantified by immunohistochemical analysis and Western blot assays. The HSV‑TK gene was successfully transfected into the HepG2 cell using ultrasound wave irradiation, and was stably expressed. Compared with the other groups, the HSV‑TK gene group treated with ATRA exhibited an increased number of apoptotic cells (Psuicide gene therapy system, which may provide a potential strategy for hepatocellular carcinoma treatment. PMID:26935255

  4. The Role of Monocarboxylate Transporters and Their Chaperone CD147 in Lactate Efflux Inhibition and the Anticancer Effects of Terminalia chebula in Neuroblastoma Cell Line N2-A

    Science.gov (United States)

    Messeha, S. S.; Zarmouh, N. O.; Taka, E.; Gendy, S. G.; Shokry, G. R.; Kolta, M. G.; Soliman, K. F. A.

    2016-01-01

    Aims In the presence of oxygen, most of the synthesized pyruvate during glycolysis in the cancer cell of solid tumors is released away from the mitochondria to form lactate (Warburg Effect). To maintain cell homeostasis, lactate is transported across the cell membrane by monocarboxylate transporters (MCTs). The major aim of the current investigation is to identify novel compounds that inhibit lactate efflux that may lead to identifying effective targets for cancer treatment. Study Design In this study, 900 ethanol plant extracts were screened for their lactate efflux inhibition using neuroblastoma (N2-A) cell line. Additionally, we investigated the mechanism of inhibition for the most potent plant extract regarding monocarboxylate transporters expression, and consequences effects on viability, growth, and apoptosis. Methodology The potency of lactate efflux inhibition of ethanol plant extracts was evaluated in N2-A cells by measuring extracellular lactate levels. Caspase 3- activity and acridine orange/ethidium bromide staining were performed to assess the apoptotic effect. The antiproliferative effect was measured using WST assay. Western blotting was performed to quantify protein expression of MCTs and their chaperone CD147 in treated cells lysates. Results Terminalia chebula plant extract was the most potent lactate efflux inhibitor in N2-A cells among the 900 - tested plant extracts. The results obtained show that extract of Terminalia chebula fruits (TCE) significantly (P = 0.05) reduced the expression of the MCT1, MCT3, MCT4 and the chaperone CD147. The plant extract was more potent (IC50 of 3.59 ± 0.26 μg/ml) than the MCT standard inhibitor phloretin (IC50 76.54 ± 3.19 μg/ml). The extract also showed more potency and selective cytotoxicity in cancer cells than DI-TNC1 primary cell line (IC50 7.37 ± 0.28 vs. 17.35 ± 0.19 μg/ml). Moreover, TCE Inhibited N2-A cell growth (IG50 = 5.20 ± 0.30 μg/ml) and induced apoptosis at the 7.5 μg/ml concentration

  5. Insights into the strong in-vitro anticancer effects for bis(triphenylphosphane)iminium compounds having perchlorate, tetrafluoridoborate and bis(chlorido)argentate anions.

    Science.gov (United States)

    Folda, Alessandra; Scalcon, Valeria; Ghazzali, Mohamed; Jaafar, Mohammed H; Khan, Rais Ahmad; Casini, Angela; Citta, Anna; Bindoli, Alberto; Rigobello, Maria Pia; Al-Farhan, Khalid; Alsalme, Ali; Reedijk, Jan

    2015-12-01

    Three new compounds containing the bis(triphenylphosphane)iminium cation (PPN(+)) with ClO4(-), BF4(-) and [AgCl2](-) as counter anions have been synthesized and structurally characterized. The two derivatives with ClO4(-) and BF4(-) were found to be isostructural by single crystal X-ray diffraction. Interestingly, the three compounds show extremely potent antiproliferative effects against the human cancer cell line SKOV3. To gain insights into the possible mechanisms of biological action, several intracellular targets have been considered. Thus, DNA binding has been evaluated, as well as the effects of the compounds on the mitochondrial function. Furthermore, the compounds have been tested as possible inhibitors of the seleno-enzyme thioredoxin reductase. PMID:26384162

  6. The NF-kappa B inhibitor, celastrol, could enhance the anti-cancer effect of gambogic acid on oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Gambogic acid (GA) is a major active ingredient of gamboge, a widely used traditional Chinese medicine that has been reported to be a potent cytotoxic agent against some malignant tumors. Many studies have shown that the NF-kappa B signaling pathway plays an important role in anti-apoptosis and the drug resistance of tumor cells during chemotherapy. In this study, the effects and mechanisms of GA and the NF-kappa B inhibitor celastrol on oral cancer cells were investigated. Three human oral squamous cell carcinoma cell lines, Tca8113, TSCC and NT, were treated with GA alone, celastrol alone or GA plus celastrol. Cytotoxicity was assessed by MTT assay. The rate of apoptosis was examined with annexin V/PI staining as well as transmission electronic microscopy in Tca8113 cells. The level of constitutive NF-kappa B activity in oral squamous cell carcinoma cell lines was determined by immunofluorescence assays and nuclear extracts and electrophoretic mobility shift assays (EMSAs) in vitro. To further investigate the role of NF-kappa B activity in GA and celastrol treatment in oral squamous cell carcinoma, we used the dominant negative mutant SR-IκBα to inhibit NF-kappa B activity and to observe its influence on the effect of GA. The results showed that GA could inhibit the proliferation and induce the apoptosis of the oral squamous cell carcinoma cell lines and that the NF-kappa B pathway was simultaneously activated by GA treatment. The minimal cytotoxic dose of celastrol was able to effectively suppress the GA-induced NF-kappa B pathway activation. Following the combined treatment with GA and the minimal cytotoxic dose of celastrol or the dominant negative mutant SR-IκBα, proliferation was significantly inhibited, and the apoptotic rate of Tca8113 cells was significantly increased. The combination of GA and celastrol has a synergistic antitumor effect. The effect can be primarily attributed to apoptosis induced by a decrease in NF-kappa B pathway activation. The

  7. Some medicinal plants as natural anticancer agents

    Directory of Open Access Journals (Sweden)

    Govind Pandey

    2009-01-01

    Full Text Available India is the largest producer of medicinal plants and is rightly called the "Botanical garden of the World". The medicinal plants, besides having natural therapeutic values against various diseases, also provide high quality of food and raw materials for livelihood. Considerable works have been done on these plants to treat cancer, and some plant products have been marketed as anticancer drugs, based on the traditional uses and scientific reports. These plants may promote host resistance against infection by re-stabilizing body equilibrium and conditioning the body tissues. Several reports describe that the anticancer activity of medicinal plants is due to the presence of antioxidants in them. In fact, the medicinal plants are easily available, cheaper and possess no toxicity as compared to the modern (allopathic drugs. Hence, this review article contains 66 medicinal plants, which are the natural sources of anticancer agents.

  8. Snake venom: a potent anticancer agent.

    Science.gov (United States)

    Jain, Deepika; Kumar, Sudhir

    2012-01-01

    Since cancer is one of the leading causes of death worldwide, and there is an urgent need to find better treatment. In recent years remarkable progress has been made towards the understanding of proposed hallmarks of cancer development and treatment. Treatment modalities comprise radiation therapy, surgery, chemotherapy, immunotherapy and hormonal therapy. Currently, the use of chemotherapeutics remains the predominant option for clinical control. However, one of the major problems with successful cancer therapy using chemotherapeutics is that patients often do not respond or eventually develop resistance after initial treatment. This has led to the increased use of anticancer drugs developed from natural resources. The biodiversity of venoms and toxins makes them a unique source from which novel therapeutics may be developed. In this review, the anticancer potential of snake venom is discussed. Some of the included molecules are under clinical trial and may find application for anticancer drug development in the near future. PMID:23244070

  9. Anticancer potential of animal venoms and toxins.

    Science.gov (United States)

    Gomes, Antony; Bhattacharjee, Pushpak; Mishra, Roshnara; Biswas, Ajoy K; Dasgupta, Subir Chandra; Giri, Biplab

    2010-02-01

    Anticancer drug development from natural resources are ventured throughout the world. Animal venoms and toxins a potential bio resource and a therapeutic tool were known to man for centuries through folk and traditional knowledge. The biodiversity of venoms and toxins made it a unique source of leads and structural templates from which new therapeutic agents may be developed. Venoms of several animal species (snake, scorpion, toad, frog etc) and their active components (protein and non protein toxins, peptides, enzymes, etc) have shown therapeutic potential against cancer. In the present review, the anticancer potential of venoms and toxins from snakes, scorpions, toads and frogs has been discussed. Some of these molecules are in the clinical trials and may find their way towards anticancer drug development in the near future. The implications of combination therapy of natural products in cancer have been discussed. PMID:20455317

  10. Methemoglobin formation by triapine, di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT), and other anticancer thiosemicarbazones: identification of novel thiosemicarbazones and therapeutics that prevent this effect.

    Science.gov (United States)

    Quach, Patricia; Gutierrez, Elaine; Basha, Maram Talal; Kalinowski, Danuta S; Sharpe, Philip C; Lovejoy, David B; Bernhardt, Paul V; Jansson, Patric J; Richardson, Des R

    2012-07-01

    Thiosemicarbazones are a group of compounds that have received comprehensive investigation as anticancer agents. The antitumor activity of the thiosemicarbazone, 3-amino-2-pyridinecarboxaldehyde thiosemicarbazone (3-AP; triapine), has been extensively assessed in more than 20 phase I and II clinical trials. These studies have demonstrated that 3-AP induces methemoglobin (metHb) formation and hypoxia in patients, limiting its usefulness. Considering this problem, we assessed the mechanism of metHb formation by 3-AP compared with that of more recently developed thiosemicarbazones, including di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT). This was investigated using intact red blood cells (RBCs), RBC lysates, purified oxyhemoglobin, and a mouse model. The chelation of cellular labile iron with the formation of a redox-active thiosemicarbazone-iron complex was found to be crucial for oxyhemoglobin oxidation. This observation was substantiated using a thiosemicarbazone that cannot ligate iron and also by using the chelator, desferrioxamine, that forms a redox-inactive iron complex. Of significance, cellular copper chelation was not important for metHb generation in contrast to its role in preventing tumor cell proliferation. Administration of Dp44mT to mice catalyzed metHb and cardiac metmyoglobin formation. However, ascorbic acid administered together with the drug in vivo significantly decreased metHb levels, providing a potential therapeutic intervention. Moreover, we demonstrated that the structure of the thiosemicarbazone is of importance in terms of metHb generation, because the DpT analog, di-2-pyridylketone-4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC), does not induce metHb generation in vivo. Hence, DpC represents a next-generation thiosemicarbazone that possesses markedly superior properties. This investigation is important for developing more effective thiosemicarbazone treatment regimens. PMID:22508546

  11. Wogonin has multiple anti-cancer effects by regulating c-Myc/SKP2/Fbw7α and HDAC1/HDAC2 pathways and inducing apoptosis in human lung adenocarcinoma cell line A549.

    Directory of Open Access Journals (Sweden)

    Xin-mei Chen

    Full Text Available Wogonin is a plant monoflavonoid which has been reported to inhibit cell growth and/or induce apoptosis in various tumors. The present study examined the apoptosis-inducing activity and underlying mechanism of action of wogonin in A549 cells. The results showed that wogonin was a potent inhibitor of the viability of A549 cells. Apoptotic protein changes detected after exposure to wogonin included decreased XIAP and Mcl-1 expression, increased cleaved-PARP expression and increased release of AIF and cytochrome C. Western blot analysis showed that the activity of c-Myc/Skp2 and HDAC1/HDAC2 pathways, which play important roles in tumor progress, was decreased. Quantitative PCR identified increased levels of c-Myc mRNA and decreased levels of its protein. Protein levels of Fbw7α, GSK3β and Thr58-Myc, which are involved in c-Myc ubiquitin-dependent degradation, were also analyzed. After exposure to wogonin, Fbw7α and GSK3β expression decreased and Thr58-Myc expression increased. However, MG132 was unable to prevent c-Myc degradation. The present results suggest that wogonin has multiple anti-cancer effects associated with degradation of c-Myc, SKP2, HDAC1 and HDAC2. Its ability to induce apoptosis independently of Fbw7α suggests a possible use in drug-resistance cancer related to Fbw7 deficiency. Further studies are needed to determine which pathways are related to c-Myc and Fbw7α reversal and whether Thr58 phosphorylation of c-Myc is dependent on GSK3β.

  12. Application of CellDesigner to the Selection of Anticancer Drug Targets: Test Case using P53

    OpenAIRE

    Isea, Raul; Hoebeke, Johan; Mayo, Rafael; Alvarez, Fernando; Holmes, David S.

    2013-01-01

    Cancer is a disease involving many genes, consequently it has been difficult to design anticancer drugs that are efficacious over a broad range of cancers. The robustness of cellular responses to gene knockout and the need to reduce undesirable side effects also contribute to the problem of effective anti-cancer drug design. To promote the successful selection of drug targets, each potential target should be subjected to a systems biology scrutiny to locate effective and specific targets whil...

  13. Farnesol inhibits tumor growth and enhances the anticancer effects of bortezomib in multiple myeloma xenograft mouse model through the modulation of STAT3 signaling pathway.

    Science.gov (United States)

    Lee, Jong Hyun; Kim, Chulwon; Kim, Sung-Hoon; Sethi, Gautam; Ahn, Kwang Seok

    2015-05-01

    Aberrant activation of signal transducer and activator of transcription 3 (STAT3) is frequently observed in multiple myeloma (MM) cancer and can upregulate the expression of several genes involved in proliferation, survival, metastasis, and angiogenesis. The effect of farnesol (FOH) on STAT3 activation, associated protein kinases, its regulated gene products, cellular proliferation, and apoptosis was examined. The in vivo effect of FOH on the growth of human MM xenograft tumors alone and in combination with bortezomib (Bor) in athymic nu/nu female mice was also investigated. We found that FOH suppressed both constitutive and inducible STAT3 activation at Tyr705 in MM cells. The suppression of STAT3 was mediated through the inhibition of activation of upstream JAK1, JAK2, and c-Src kinases. Also, treatment with the protein tyrosine phosphatase (PTP) inhibitor, pervanadate treatment reversed the FOH-induced down-regulation of STAT3, possibly indicating the involvement of a PTP. Indeed, we found that FOH treatment induces the increased expression of SHP-2 protein and knockdown of the SHP-2 gene by small interfering RNA suppressed the ability of FOH to inhibit STAT3 activation. FOH inhibited proliferation and significantly potentiated the apoptotic effects of bortezomib (Bor) in U266 cells. When administered intraperitoneally, FOH enhanced Bor-induced growth suppression of human MM xenograft tumors in athymic nu/nu female mice. Our results suggest that FOH is a novel blocker of STAT3 signaling pathway and exerts both anti-proliferative and apoptotic activities in MM in vitro and in vivo. PMID:25697480

  14. Effect of anticancer drugs on breast cancer cells sensitive and resistant to doxorubicin: expression of mRNAs of TGF-β and its receptors

    OpenAIRE

    Chorna I. V.; Fedorenko O. V.; Stoika R. S.

    2014-01-01

    Aim. Comparative study of the effect of chemotherapeutic drugs (doxorubicin, methotrexate and cisplatin) and TGF-β on the human breast carcinoma MCF-7 cells, sensitive (wt) and resistant (DOX/R) to the doxorubicin action. Methods. Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was used for the estimation of expression of mRNAs coding for the TGF-β isoforms (TGF-β1 and TGF-β2) and the TGF-β type I and II receptors (TRI and TRII). Trypan blue exclusion method was use...

  15. Anticancer effects of tributyltin chloride and triphenyltin chloride in human breast cancer cell lines MCF-7 and MDA-MB-231.

    Science.gov (United States)

    Hunakova, Luba; Macejova, D; Toporova, L; Brtko, J

    2016-05-01

    Triorganotin compounds induce hormonal alterations, i.e., endocrine-disrupting effects in mammals, including humans. Tributyltin chloride (TBT-Cl) and triphenyltin chloride (TPT-Cl) are known to function as nuclear retinoid X receptor (RXR) agonists. Their cytotoxic effects in ER(+) luminal human breast cancer cell line MCF-7 and ER(-) basal-like human breast cancer cell line MDA-MB-231 were examined. We observed significantly higher toxicity of TBT-Cl in comparison with TPT-Cl in both cell lines. Comparable apoptosis-inducing concentrations were 200 and 800 nM, respectively, as shown by PARP cleavage and FDA staining. Both compounds activated executive caspases in the concentration-dependent manner in MDA-MB-231 cells, but the onset of TPT-Cl-induced caspase-3/7 activation was delayed in comparison with TBT-Cl. Both compounds slowed down the migration of these highly invasive cells, which was accompanied by RARbeta upregulation. Other RAR and RXR expressions were differentially modulated by studied organotins in both cell lines. PMID:26662104

  16. 2-phenylethynesulphonamide (PFT-μ) enhances the anticancer effect of the novel hsp90 inhibitor NVP-AUY922 in melanoma, by reducing GSH levels.

    Science.gov (United States)

    Yeramian, Andree; Vea, Alvar; Benítez, Sandra; Ribera, Joan; Domingo, Mónica; Santacana, Maria; Martinez, Montserrat; Maiques, Oscar; Valls, Joan; Dolcet, Xavier; Vilella, Ramón; Cabiscol, Elisa; Matias-Guiu, Xavier; Marti, Rosa M

    2016-05-01

    Heat shock proteins (HSPs), are molecular chaperones that assist the proper folding of nascent proteins. This study aims to evaluate the antitumour effects of the hsp90 inhibitor NVP-AUY922 in melanoma, both in vitro and in vivo. Our results show that NVP-AUY922 inhibits melanoma cell growth in vitro, with down regulation of multiple signalling pathways involved in melanoma progression such as NF-ĸB and MAPK/ERK. However, NVP-AUY922 was unable to limit tumour growth in vivo. Cotreatment of A375M xenografts with NVP-AUY922 and PFT-μ, a dual inhibitor of both hsp70 and autophagy, induced a synergistic increase of cell death in vitro, and delayed tumour formation in A375M xenografts. PFT-μ depleted cells from the reduced form of glutathione (GSH) and increased oxidative stress. The oxidative stress induced by PFT-μ further enhanced NVP-AUY922-induced cytotoxic effects. These data suggest a potential therapeutic role for NVP-AUY922 used in combination with PFT-μ, in melanoma. PMID:26988132

  17. Biological Effect of a Hybrid Anticancer Agent Based on Kinase and Histone Deacetylase Inhibitors on Triple-Negative (MDA-MB231) Breast Cancer Cells.

    Science.gov (United States)

    Librizzi, Mariangela; Spencer, John; Luparello, Claudio

    2016-01-01

    We examined the effects of the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA) combined with the vascular endothelial growth factor receptor-1/2 inhibitor (3Z)-5-hydroxy-3-(1H-pyrrol-2-ylmethylidene)-2,3-dihydro-1H-indol-2-one on MDA-MB-231 breast cancer cells (triple-negative) in the form of both a cocktail of the separate compounds and a chemically synthesized hybrid (N-hydroxy-N'-[(3Z)-2-oxo-3-(1H-pyrrol-2-ylmethylidene)-2,3-dihydro-1H-indol-5-yl]octanediamide). Comparative flow cytometric and Western blot analyses were performed on cocktail- and hybrid-treated cells to evaluate cell cycle distribution, autophagy/apoptosis modulation, and mitochondrial metabolic state in order to understand the cellular basis of the cytotoxic effect. Cell cycle analysis showed a perturbation of the rate of progression through the cycle, with aspects of redistribution of cells over different cycle phases for the two treatments. In addition, the results suggest that the two distinct classes of compounds under investigation could induce cell death by different preferential pathways, i.e., autophagy inhibition (the cocktail) or apoptosis promotion (the hybrid), thus confirming the enhanced potential of the hybrid approach vs. the combination approach in finely tuning the biological activities of target cells and also showing the hybrid compound as an additional promising drug-like molecule for the prevention or therapy of "aggressive" breast carcinoma. PMID:27483253

  18. Indomethacin-Enhanced Anticancer Effect of Arsenic Trioxide in A549 Cell Line: Involvement of Apoptosis and Phospho-ERK and p38 MAPK Pathways

    Directory of Open Access Journals (Sweden)

    Ali Mandegary

    2013-01-01

    Full Text Available Background. Focusing on novel drug combinations that target different pathways especially apoptosis and MAPK could be a rationale for combination therapy in successful treatment of lung cancer. Concurrent use of cyclooxygenase (COX inhibitors with arsenic trioxide (ATO might be a possible treatment option. Methods. Cytotoxicity of ATO, dexamethasone (Dex, celecoxib (Cel, and Indomethacin (Indo individually or in combination was determined at 24, 48, and 72 hrs in A549 lung cancer cells. The COX-2 gene and protein expression, MAPK pathway proteins, and caspase-3 activity were studied for the most cytotoxic combinations. Results. The IC50s of ATO and Indo were 68.7 μmol/L and 396.5 μmol/L, respectively. Treatment of cells with combinations of clinically relevant concentrations of ATO and Indo resulted in greater growth inhibition and apoptosis induction than did either agent alone. Caspase-3 activity was considerably high in the presence of ATO and Indo but showed no difference in single or combination use. Phosphorylation of p38 and ERK1/2 was remarkable in the concurrent presence of both drugs. Conclusions. Combination therapy with ATO and Indo exerted a very potent in vitro cytotoxic effect against A549 lung cancer cells. Activation of ERK and p38 pathways might be the mechanism of higher cytotoxic effect of ATO-Indo combination.

  19. 鹅绒委陵菜多糖抗肿瘤作用研究%Anticancer Effects of Polysaccharide from Potentilla anserine L.

    Institute of Scientific and Technical Information of China (English)

    刘素君; 李世元; 宋九华; 江南; 曹玫

    2011-01-01

    目的 探讨鹅绒委陵莱多糖(PAP)的抗肿瘤作用.方法 采用MTT法研究PAP对体外培养人肝癌细胞SMMC-7721的增殖抑制作用;并将S180荷瘤小鼠随机分组.灌胃给予50,100,200 mg·kg~-1剂量的PAP,研究PAP对荷瘤小鼠的抑瘤率和免疫功能的影响.结果 体外实验结果显示PAP对SMMC-7721细胞的体外增殖有显著抑制作用,400 mg·L~-1 PAP组抑制率最高.为43.57%;PAP时人肝癌SMMC-7721细胞的抑制作用呈剂量依赖性,拟合曲线呈线性相关.动物实验结果显示低、中、高3个剂量的PAP对S180荷瘤小鼠的抑瘤率分别为46.41%,52.29%和59.48%,其中环磷酰胺和低剂量的多糖组合抑瘤率与中、高剂量的多糖抑瘤率相当,并显著高于单用环磷酰胺组的抑瘤率;同时PAP能够显著提高T-淋巴细胞和巨噬细胞吞噬率.结论 PAP具有抗肿瘤活性和增强免疫的功能.%OBJECTIVE To study the antitumor effects and immunological function of polysaccharide from Potentilla anserine L.(PAP) in vivo and in vitro. METHODS The SMMC-7721 cells were treated with different concentration of PAP.The effects of PAP on proliferation of human hepatoma SMMC-7721 cell were examined by MTT assay in vitro, and the relative results were fitted with mathematical model. The Sl80-bearing mice were intragastrically administered with 50, 100, 200 mg·kg-1 PAP, respectively. The inhibition rate of S180 tumor and immunological function of PAP were measured in vivo.RESULTS The effects on proliferation of SMMC-7721 cell were correlated with the concentration of PAP in vitro. The highest inhibition was 43.57% at the dose of 400 mg·L-1 PAP. The effects and PAP concentration were correlated and regressed. The inhibiting tumor rates were 46.41%, 52.29% and 59.48% in different groups treated with 50, 100 and 200 mg·kg-1 in vivo,respectively. The T-lymphocytes and macrophage phagocytic index increased significantly after the effects of PAP in S180-bearing mice. CONCLUSION

  20. Studies with Myrtus communis L.: Anticancer properties.

    Science.gov (United States)

    Ogur, Recai

    2014-01-01

    Myrtus communis (MC) L. is a well-known Mediterranean plant with important cultural significance in this region. In ancient times, MC was accepted as a symbol of immortality. Maybe due to this belief, it is used during cemetery visits in some regions. Although it is a well-known plant in cosmetics, and there is a lot of studies about its different medical properties, anticancer studies performed using its different extracts or oils are not so much, but increasing. We collected these anticancer property-related studies in this review. PMID:26401362

  1. 17β-estradiol exerts anticancer effects in anoikis-resistant hepatocellular carcinoma cell lines by targeting IL-6/STAT3 signaling.

    Science.gov (United States)

    Lee, Seulki; Lee, Minjong; Kim, Jong Bin; Jo, Ara; Cho, Eun Ju; Yu, Su Jong; Lee, Jeong-Hoon; Yoon, Jung-Hwan; Kim, Yoon Jun

    2016-05-13

    17β-Estradiol (E2) has been proven to exert protective effects against HCC; however, its mechanism on HCC proliferation and suppression of invasion remains to be further explored. Because HCC up-regulates serum Interleukin-6 (IL-6) levels and Signal Transducer and Activator of Transcription 3 (STAT3), molecular agents that attenuate IL-6/STAT3 signaling can potentially suppress HCC development. In this study, we examined involvement of E2 in anoikis resistance that induces invasion capacities and chemo-resistance. Huh-BAT and HepG2 cells grown under anchorage-independent condition were selected. The anoikis-resistant (AR) cells showed stronger chemo-resistance against sorafenib, doxorubicin, 5-fluorouracil and cisplatin compared to adherent HCC cells. AR HCC cells exhibited decreased expression of E-cadherin and increased expression of the N-cadherin and vimentin compared to adherent HCC cells. We then demonstrated that E2 suppressed cell proliferation in AR HCC cells. IL-6 treatment enhanced invasive characteristics, and E2 reversed it. Regarding mechanism of E2, it decreased in the phosphorylation of STAT3 that overexpressed on AR HCC cells. The inhibitory effect of E2 on cell growth was accompanied with cell cycle arrest at G2/M phase and caspase-3/9/PARP activation through c-Jun N-terminal Kinase (JNK) phosphorylation. Taken together, these findings suggested that E2 inhibited the proliferation of AR HCC cells through down-regulation of IL-6/STAT3 signaling. Thus, E2 can be a potential therapeutic drug for treatment of metastatic or chemo-resistant HCC. PMID:27091428

  2. Use of proteasome inhibitors in anticancer therapy

    Directory of Open Access Journals (Sweden)

    Sara M. Schmitt

    2011-10-01

    Full Text Available The importance of the ubiquitin-proteasome pathway to cellular function has brought it to the forefront in the search for new anticancer therapies. The ubiquitin-proteasome pathway has proven promising in targeting various human cancers. The approval of the proteasome inhibitor bortezomib for clinical treatment of relapsed/refractory multiple myeloma and mantle cell lymphoma has validated the ubiquitin-proteasome as a rational target. Bortezomib has shown positive results in clinical use but some toxicity and side effects, as well as resistance, have been observed, indicating that further development of novel, less toxic drugs is necessary. Because less toxic drugs are necessary and drug development can be expensive and time-consuming, using existing drugs that can target the ubiquitin-proteasome pathway in new applications, such as cancer therapy, may be effective in expediting the regulatory process and bringing new drugs to the clinic. Toward this goal, previously approved drugs, such as disulfiram, as well as natural compounds found in common foods, such as green tea polyphenol (--EGCG and the flavonoid apigenin, have been investigated for their possible proteasome inhibitory and cell death inducing abilities. These compounds proved quite promising in preclinical studies and have now moved into clinical trials, with preliminary results that are encouraging. In addition to targeting the catalytic activity of the proteasome pathway, upstream regulators, such as the 19S regulatory cap, as well as E1, E2, and E3, are now being investigated as potential drug targets. This review outlines the development of novel proteasome inhibitors from preclinical to clinical studies, highlighting their abilities to inhibit the tumor proteasome and induce apoptosis in several human cancers.

  3. Dendrophthoe falcata (L.f) Ettingsh (Neem mistletoe): A potent bioresource to fabricate silver nanoparticles for anticancer effect against human breast cancer cells (MCF-7)

    Science.gov (United States)

    Sathishkumar, Gnanasekar; Gobinath, Chandrakasan; Wilson, Arockiyasamy; Sivaramakrishnan, Sivaperumal

    2014-07-01

    Fabrication of metal nano scale particles through environmentally acceptable greener route has been focused with much interest in the present scenario. In this study aqueous leaf extract of mistletoe Dendrophthoe falcata (L.f) Ettingsh was successfully employed as a reducing and stabilizing agent to fabricate nanosilver particles (AgNPs) for biomedical applications. Various reactions conditions such as temperature, pH, concentration of metal ion, incubation time and stoichiometric proportion of the reaction mixture were optimized to attain narrow size range particles with maximum synthesis rate. Fabricated crystalline AgNPs with spherical structure (5-45 nm) were characterized with UV-Visible spectroscopy, Field emission scanning electron microscope (FESEM), High resolution transmission electron microscope (HRTEM) and Selected area diffraction pattern (SEAD). Further the fabricated AgNPs were studied for their stability and surface chemistry through Fourier transform infrared spectroscopy (FTIR), Energy dispersive X-ray spectroscopy (EDAX) and inductively coupled plasma optical emission spectroscopy (ICP-OES). Moreover, fabricated AgNPs and aqueous leaf extract were assessed for their cytotoxicity effect against human breast carcinoma cell line (MCF-7). It is concluded that colloidal AgNPs can be developed as an imminent candidature for cancer therapy.

  4. Anti-cancer effects of enteric-coated polymers containing mistletoe lectin in murine melanoma cells in vitro and in vivo.

    Science.gov (United States)

    Han, Seung-Yeon; Hong, Chang-Eui; Kim, Hwan-Gyu; Lyu, Su-Yun

    2015-10-01

    In this study, we evaluated the effects of Korean mistletoe (Viscum album L. var. coloratum) coated with a biodegradable polymer (Eudragit(®)) wall on the growth of mouse melanoma in vivo. Oral administration of 4% (430 mg/kg/day) enteric-coated mistletoe resulted in a significant reduction in tumor volume on day 14 compared to the negative control group in B16F10 melanoma-inoculated BDF1 mice. When we measured the survival rate, enteric-coated mistletoe-received mice had a higher survival rate after day 12. Also, we investigated the mechanism involving the cancer cell growth inhibition when melanoma cells were treated with Korean mistletoe lectin (Viscum album L. var. coloratum agglutinin, VCA) and its extract in vitro. As a result, a significant G0/G1 arrest was observed in both B16BL6 and B16F10 melanoma cells with VCA or mistletoe extract. In addition, VCA or mistletoe extract induced an increase in both early and late apoptosis in cells. When we studied the molecular mechanism, our results showed that VCA and mistletoe extract can increase activated multiple caspases (caspase-1, 3, 4, 5, 6, 7, 8, and 9), dose-dependently. We also found out that VCA and mistletoe treatment causes a significant decrease in the expression of procaspase-3 and 8. PMID:26152904

  5. A new class of hybrid anticancer agents inspired by the synergistic effects of curcumin and genistein: Design, synthesis, and anti-proliferative evaluation.

    Science.gov (United States)

    Chen, Qiao-Hong; Yu, Kevin; Zhang, Xiaojie; Chen, Guanglin; Hoover, Andrew; Leon, Francisco; Wang, Rubing; Subrahmanyam, Nithya; Addo Mekuria, Ermias; Harinantenaina Rakotondraibe, Liva

    2015-10-15

    Inspired by the synergistic effects of dietary natural products with different scaffolds on the inhibition of cancer cell proliferation, incorporation of central (1E,4E)-1,4-penta-dien-3-one linker (an optimal substitute for the central metabolically unstable diketone linker of curcumin), 1-alkyl-1H-imidazol-2-yl (a promising bioisostere of terminal aryl group in curcumin), and chromone (the common pharmacophore in genistein and quercetin) into one chemical entity resulted in ten new hybrid molecules, 3-((1E,4E)-5-(1-alkyl-1H-imidazol-2-yl)-3-oxopenta-1,4-dien-1-yl)-4H-chromen-4-ones. They were synthesized through a three-step transformation using acid-catalyzed aldol condensation as key step. The WST-1 cell proliferation assay showed that they have greater anti-proliferative potency than curcumin, quercetin, and genistein on both androgen-dependent and androgen-independent human prostate cancer cells. PMID:26341135

  6. Early prediction of anticancer effects with diffusion-weighted MR imaging in patients with colorectal liver metastases following selective internal radiotherapy

    International Nuclear Information System (INIS)

    To prospectively evaluate diffusion-weighted imaging (DWI) for early prediction of tumour response in patients with colorectal liver metastases following selective internal radiotherapy (SIRT). We evaluated 41 metastases in 21 patients, age 62.9 ± 9.9 years. All patients underwent magnetic resonance imaging (MRI) including breath-hold echoplanar DWI sequences. Imaging was performed before therapy (baseline MRI), 2 days after SIRT (early MRI) as well as 6 weeks later (follow-up MRI). Tumour volume (TV) and intratumoural apparent diffusion coefficient (ADC) were measured independently by two radiologists at all time points. Metastases were categorised as responding lesions (RL; n = 33) or non-responding lesions (NRL; n = 8) according to changes in TV after 6 weeks. We found an inverse correlation of changes in TV and ADC at follow-up MRI with a Pearson's correlation coefficient of r = -0.66 (p < 0.0001). On early MRI, no significant changes in TV were found for either RL or NRL. Conversely, ADC decreased significantly in RL by 10.7 ± 8.4% (p < 0.0001). ADC increased in NRL by 9.6 ± 20.8%, which was not statistically significant (p = 0.40). DWI was capable of predicting therapy effects of SIRT in patients with colorectal hepatic metastases as early as 2 days following treatment. (orig.)

  7. Curcumin AntiCancer Studies in Pancreatic Cancer

    Science.gov (United States)

    Bimonte, Sabrina; Barbieri, Antonio; Leongito, Maddalena; Piccirillo, Mauro; Giudice, Aldo; Pivonello, Claudia; de Angelis, Cristina; Granata, Vincenza; Palaia, Raffaele; Izzo, Francesco

    2016-01-01

    Pancreatic cancer (PC) is one of the deadliest cancers worldwide. Surgical resection remains the only curative therapeutic treatment for this disease, although only the minority of patients can be resected due to late diagnosis. Systemic gemcitabine-based chemotherapy plus nab-paclitaxel are used as the gold-standard therapy for patients with advanced PC; although this treatment is associated with a better overall survival compared to the old treatment, many side effects and poor results are still present. Therefore, new alternative therapies have been considered for treatment of advanced PC. Several preclinical studies have demonstrated that curcumin, a naturally occurring polyphenolic compound, has anticancer effects against different types of cancer, including PC, by modulating many molecular targets. Regarding PC, in vitro studies have shown potent cytotoxic effects of curcumin on different PC cell lines including MiaPaCa-2, Panc-1, AsPC-1, and BxPC-3. In addition, in vivo studies on PC models have shown that the anti-proliferative effects of curcumin are caused by the inhibition of oxidative stress and angiogenesis and are due to the induction of apoptosis. On the basis of these results, several researchers tested the anticancer effects of curcumin in clinical trials, trying to overcome the poor bioavailability of this agent by developing new bioavailable forms of curcumin. In this article, we review the results of pre-clinical and clinical studies on the effects of curcumin in the treatment of PC. PMID:27438851

  8. Curcumin AntiCancer Studies in Pancreatic Cancer.

    Science.gov (United States)

    Bimonte, Sabrina; Barbieri, Antonio; Leongito, Maddalena; Piccirillo, Mauro; Giudice, Aldo; Pivonello, Claudia; de Angelis, Cristina; Granata, Vincenza; Palaia, Raffaele; Izzo, Francesco

    2016-01-01

    Pancreatic cancer (PC) is one of the deadliest cancers worldwide. Surgical resection remains the only curative therapeutic treatment for this disease, although only the minority of patients can be resected due to late diagnosis. Systemic gemcitabine-based chemotherapy plus nab-paclitaxel are used as the gold-standard therapy for patients with advanced PC; although this treatment is associated with a better overall survival compared to the old treatment, many side effects and poor results are still present. Therefore, new alternative therapies have been considered for treatment of advanced PC. Several preclinical studies have demonstrated that curcumin, a naturally occurring polyphenolic compound, has anticancer effects against different types of cancer, including PC, by modulating many molecular targets. Regarding PC, in vitro studies have shown potent cytotoxic effects of curcumin on different PC cell lines including MiaPaCa-2, Panc-1, AsPC-1, and BxPC-3. In addition, in vivo studies on PC models have shown that the anti-proliferative effects of curcumin are caused by the inhibition of oxidative stress and angiogenesis and are due to the induction of apoptosis. On the basis of these results, several researchers tested the anticancer effects of curcumin in clinical trials, trying to overcome the poor bioavailability of this agent by developing new bioavailable forms of curcumin. In this article, we review the results of pre-clinical and clinical studies on the effects of curcumin in the treatment of PC. PMID:27438851

  9. Positive effects on hematological and biochemical imbalances in patients with metastatic breast cancer stage IV, of BP-C1, a new anticancer substance

    Directory of Open Access Journals (Sweden)

    Lindkær-Jensen S

    2015-03-01

    Full Text Available Steen Lindkær-Jensen,1 Stig Larsen,2 Nina Habib-Lindkær-Jensen,1 Hans E Fagertun3 1Department of Surgery and Cancer, Hammersmith Hospital Campus, Imperial College, London, UK; 2Center of Epidemiology and Biostatistics, Faculty of Veterinary Medicine, University of Life Science, Oslo, Norway; 3Meddoc Research AS, Skjetten, Norway Abstract: A benzene-poly-carboxylic acid complex with cis-diammineplatinum(II dihydrocholride, BP-C1 is currently used in clinical trials in treating metastatic breast cancer. BP-C1 controls tumor growth with a few mild side-effects, improving quality of life.Methods: The data consisted of prospectively collected laboratory results from 47 patients in two controlled clinical trials of daily intramuscular injections of BP-C1 for 32 days. Study I was performed as an open, nonrandomized, Phase I dose–response, multicenter study with a three-level, between-patient, response surface pathway design. The second study was a randomized, double-blind, and placebo-controlled, multicenter study with a stratified semi-crossover design.Results: Hemoglobin (Hb and hematocrit (Hct increased significantly (P<0.01 during BP-C1 treatment, while red blood cell (RBC count increased but not significantly. The most pronounced increase in Hb, RBC, Hct, and white blood cell (WBC was in anemic patients (P≤0.01. WBC count and neutrophils increased significantly (P=0.01 in the overall data. WBCs and neutrophils (P<0.01, eosinophils (P=0.05 and monocytes (P<0.01 increased significantly and markedly in patients with lowest baseline levels. Additionally, low levels of thrombocytes significantly increased. No changes in liver parameters, amylase, glucose, creatinine, or albumin, were detected except for albumin in the subgroup with low baseline levels, where levels increased significantly (P=0.04. An increase in K+, Ca2+, and PO43- was most pronounced in patients with low baseline levels (P≤0.02. A similar pattern detected for Mg2+, prothrombin

  10. Positive effects on hematological and biochemical imbalances in patients with metastatic breast cancer stage IV, of BP-C1, a new anticancer substance

    Science.gov (United States)

    Lindkær-Jensen, Steen; Larsen, Stig; Habib-Lindkær-Jensen, Nina; Fagertun, Hans E

    2015-01-01

    A benzene-poly-carboxylic acid complex with cis-diammineplatinum(II) dihydrocholride, BP-C1 is currently used in clinical trials in treating metastatic breast cancer. BP-C1 controls tumor growth with a few mild side-effects, improving quality of life. Methods The data consisted of prospectively collected laboratory results from 47 patients in two controlled clinical trials of daily intramuscular injections of BP-C1 for 32 days. Study I was performed as an open, nonrandomized, Phase I dose–response, multicenter study with a three-level, between-patient, response surface pathway design. The second study was a randomized, double-blind, and placebo-controlled, multicenter study with a stratified semi-crossover design. Results Hemoglobin (Hb) and hematocrit (Hct) increased significantly (P<0.01) during BP-C1 treatment, while red blood cell (RBC) count increased but not significantly. The most pronounced increase in Hb, RBC, Hct, and white blood cell (WBC) was in anemic patients (P≤0.01). WBC count and neutrophils increased significantly (P=0.01) in the overall data. WBCs and neutrophils (P<0.01), eosinophils (P=0.05) and monocytes (P<0.01) increased significantly and markedly in patients with lowest baseline levels. Additionally, low levels of thrombocytes significantly increased. No changes in liver parameters, amylase, glucose, creatinine, or albumin, were detected except for albumin in the subgroup with low baseline levels, where levels increased significantly (P=0.04). An increase in K+, Ca2+, and PO43− was most pronounced in patients with low baseline levels (P≤0.02). A similar pattern detected for Mg2+, prothrombin time (PT), coagulation factors II, VII, X (KFNT), and C-reactive protein (CRP), which increased significantly (P≤0.05) in the groups with the lowest values. Conclusion Our findings support the safety profile of BP-C1 use in cancer patients. BP-C1 did not induce anemia, infection, bleeding, hepatic insufficiency or electrolyte imbalances. In

  11. SRJ09, a promising anticancer drug lead: Elucidation of mechanisms of antiproliferative and apoptogenic effects and assessment of in vivo antitumor efficacy.

    Science.gov (United States)

    Wong, Charng Choon; Lim, Siang Hui; Sagineedu, Sreenivasa Rao; Lajis, Nordin Haji; Stanslas, Johnson

    2016-05-01

    SRJ09 (3,19-(2-bromobenzylidene)andrographolide), a semisynthetic andrographolide (AGP) derivative, was shown to induce G1 cell cycle arrest and eventually apoptosis in breast and colon cancer cell lines. The present investigation was carried out to elucidate the mechanisms cell cycle arrest and apoptosis and evaluate the in vivo antitumor activity of SRJ09. The in vitro growth inhibitory properties of compounds were assessed in colon (HCT-116) and breast (MCF-7) cancer cell lines. Immunoblotting was utilized to quantitate the protein levels in cells. The gene expressions were determined using reverse transcriptase PCR (RT-PCR). Pharmacokinetic investigation was carried out by determining SRJ09 levels in plasma of Balb/C mice using HPLC. In vivo antitumor activity was evaluated in athymic mice carrying HCT-116 colon tumor xenografts. SRJ09 displayed improved in vitro activity when compared with AGP by producing rapid cell killing effect in vitro. Its activity was not compromised in MES-SA/Dx5 multidrug resistant (MDR) cells expressing p-glycoprotein. Cells treated with SRJ09 (0.1-10μM) displayed increased p21 protein level, which corresponded with gene expression. Whereas CDK4 protein level and gene expression was suppressed. The treatment did not affect cyclin D1. Changes of these proteins paralleled G1 cell cycle arrest in both cell lines as determined by flow cytometry. Induction of apoptosis by SRJ09 in HCT-116 cells which occurred independent of p53 and bcl-2 was inhibited in the presence of caspase 8 inhibitor, implicating the extrinsic apoptotic pathway. A single dose (100mg/kg, i.p) of SRJ09 produced a plasma concentration range of 12-30.4μM. At 400mg/kg (q4dX3), it significantly retarded growth of tumor xenografts. The antitumor activity of SRJ09 is suggested mediated via the induction of p21 expression and suppression of CDK-4 expression without affecting cyclin D1 to trigger G1 arrest leading to apoptosis. PMID:26940565

  12. Down-regulation of 14-3-3β exerts anti-cancer effects through inducing ER stress in human glioma U87 cells: Involvement of CHOP–Wnt pathway

    Energy Technology Data Exchange (ETDEWEB)

    Cao, Lei; Lei, Hui; Chang, Ming-Ze; Liu, Zhi-Qin [Department of Neurological Disease, Xi' an Central Hospital, Xi' an Jiaotong University, Xi' an, Shaanxi 710000 (China); Bie, Xiao-Hua, E-mail: biexiaohua_xjtu@126.com [Department of Functional Neurosurgery, Xi' an Red Cross Hospital, Xi' an Jiaotong University, Xi' an, Shaanxi 710054 (China)

    2015-07-10

    We previously identified 14-3-3β as a tumor-specific isoform of 14-3-3 protein in astrocytoma, but its functional role in glioma cells and underlying mechanisms are poorly understood. In the present study, we investigated the effects of 14-3-3β inhibition in human glioma U87 cells using specific targeted small interfering RNA (siRNA). The results showed that 14-3-3β is highly expressed in U87 cells but not in normal astrocyte SVGp12 cells. Knockdown of 14-3-3β by Si-14-3-3β transfection significantly decreased the cell viability but increased the LDH release in a time-dependent fashion in U87 cells, and these effects were accompanied with G0/G1 cell cycle arrest and apoptosis. In addition, 14-3-3β knockdown induced ER stress in U87 cells, as evidenced by ER calcium release, increased expression of XBP1S mRNA and induction of ER related pro-apoptotic factors. Down-regulation of 14-3-3β significantly decreased the nuclear localization of β-catenin and inhibited Topflash activity, which was shown to be reversely correlated with CHOP. Furthermore, Si-CHOP and sFRP were used to inhibit CHOP and Wnt, respectively. The results showed that the anti-cancer effects of 14-3-3β knockdown in U87 cells were mediated by increased expression of CHOP and followed inhibition of Wnt/β-catenin pathway. In summary, the remarkable efficiency of 14-3-3β knockdown to induce apoptotic cell death in U87 cells may find therapeutic application for the treatment of glioma patients. - Highlights: • Knockdown of 14-3-3β leads to cytotoxicity in human glioma U87 cells. • Knockdown of 14-3-3β induces cell cycle arrest and apoptosis in U87 cells. • Knockdown of 14-3-3β results in ER stress in U87 cells. • Knockdown of 14-3-3β inhibits Wnt/β-catenin pathway via CHOP activation.

  13. Down-regulation of 14-3-3β exerts anti-cancer effects through inducing ER stress in human glioma U87 cells: Involvement of CHOP–Wnt pathway

    International Nuclear Information System (INIS)

    We previously identified 14-3-3β as a tumor-specific isoform of 14-3-3 protein in astrocytoma, but its functional role in glioma cells and underlying mechanisms are poorly understood. In the present study, we investigated the effects of 14-3-3β inhibition in human glioma U87 cells using specific targeted small interfering RNA (siRNA). The results showed that 14-3-3β is highly expressed in U87 cells but not in normal astrocyte SVGp12 cells. Knockdown of 14-3-3β by Si-14-3-3β transfection significantly decreased the cell viability but increased the LDH release in a time-dependent fashion in U87 cells, and these effects were accompanied with G0/G1 cell cycle arrest and apoptosis. In addition, 14-3-3β knockdown induced ER stress in U87 cells, as evidenced by ER calcium release, increased expression of XBP1S mRNA and induction of ER related pro-apoptotic factors. Down-regulation of 14-3-3β significantly decreased the nuclear localization of β-catenin and inhibited Topflash activity, which was shown to be reversely correlated with CHOP. Furthermore, Si-CHOP and sFRP were used to inhibit CHOP and Wnt, respectively. The results showed that the anti-cancer effects of 14-3-3β knockdown in U87 cells were mediated by increased expression of CHOP and followed inhibition of Wnt/β-catenin pathway. In summary, the remarkable efficiency of 14-3-3β knockdown to induce apoptotic cell death in U87 cells may find therapeutic application for the treatment of glioma patients. - Highlights: • Knockdown of 14-3-3β leads to cytotoxicity in human glioma U87 cells. • Knockdown of 14-3-3β induces cell cycle arrest and apoptosis in U87 cells. • Knockdown of 14-3-3β results in ER stress in U87 cells. • Knockdown of 14-3-3β inhibits Wnt/β-catenin pathway via CHOP activation

  14. Anticancer and antiproliferative activity of natural brassinosteroids

    Czech Academy of Sciences Publication Activity Database

    Malíková, J.; Swaczynová, Jana; Kolář, Z.; Strnad, Miroslav

    2008-01-01

    Roč. 69, č. 2 (2008), s. 418-426. ISSN 0031-9422 Institutional research plan: CEZ:AV0Z50380511 Keywords : Brassinosteroids * Anticancer activity * Cell cycle Subject RIV: CE - Biochemistry Impact factor: 2.946, year: 2008

  15. Gut in local and systemic anticancer response

    Czech Academy of Sciences Publication Activity Database

    Vannucci, Luca

    Praha: Carolinum, 2012. s. 31-31. ISBN 978-80-7395-456-7. [International Nutrition and Diagnostics Conference /12./. 27.08.2012-30.08.2012, Praha] R&D Projects: GA AV ČR IAA500200917 Institutional research plan: CEZ:AV0Z50200510 Keywords : Colorectal cancer * gut * anticancer response Subject RIV: EC - Immunology

  16. Anticancer activity of Ficus religiosa engineered copper oxide nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Sankar, Renu; Maheswari, Ramasamy; Karthik, Selvaraju [Department of Biochemistry, School of Life Sciences, Bharathidasan University, Tiruchirappalli 620 024, Tamilnadu (India); Shivashangari, Kanchi Subramanian, E-mail: shivashangari@gmail.com [Regional Forensic Science Laboratory, Tiruchirapalli, Tamilnadu (India); Ravikumar, Vilwanathan, E-mail: ravikumarbdu@gmail.com [Department of Biochemistry, School of Life Sciences, Bharathidasan University, Tiruchirappalli 620 024, Tamilnadu (India)

    2014-11-01

    The design, synthesis, characterization and application of biologically synthesized nanomaterials have become a vital branch of nanotechnology. There is a budding need to develop a method for environmentally benign metal nanoparticle synthesis, that do not use toxic chemicals in the synthesis protocols to avoid adverse effects in medical applications. Here, it is a report on an eco-friendly process for rapid synthesis of copper oxide nanoparticles using Ficus religiosa leaf extract as reducing and protecting agent. The synthesized copper oxide nanoparticles were confirmed by UV–vis spectrophotometer, absorbance peaks at 285 nm. The copper oxide nanoparticles were analyzed with field emission-scanning electron microscope (FE-SEM), Fourier transform infrared (FT-IR) spectroscopy, dynamic light scattering (DLS) and X-ray diffraction (XRD) spectrum. The FE-SEM and DLS analyses exposed that copper oxide nanoparticles are spherical in shape with an average particle size of 577 nm. FT-IR spectral analysis elucidates the occurrence of biomolecules required for the reduction of copper oxide ions. Zeta potential studies showed that the surface charge of the formed nanoparticles was highly negative. The XRD pattern revealed that synthesized nanoparticles are crystalline in nature. Further, biological activities of the synthesized nanoparticles were confirmed based on its stable anti-cancer effects. The apoptotic effect of copper oxide nanoparticles is mediated by the generation of reactive oxygen species (ROS) involving the disruption of mitochondrial membrane potential (Δψm) in A549 cells. The observed characteristics and results obtained in our in vitro assays suggest that the copper nanoparticles might be a potential anticancer agent. - Highlights: • Biogenic synthesis of copper oxide nanoparticles by leaf extract of Ficus religiosa • Characterized via UV–vis, FT-IR, DLS, FE-SEM with EDAX and XRD • Protein may act as an encapsulating, reducing and stabilizing

  17. Anticancer activity of Ficus religiosa engineered copper oxide nanoparticles

    International Nuclear Information System (INIS)

    The design, synthesis, characterization and application of biologically synthesized nanomaterials have become a vital branch of nanotechnology. There is a budding need to develop a method for environmentally benign metal nanoparticle synthesis, that do not use toxic chemicals in the synthesis protocols to avoid adverse effects in medical applications. Here, it is a report on an eco-friendly process for rapid synthesis of copper oxide nanoparticles using Ficus religiosa leaf extract as reducing and protecting agent. The synthesized copper oxide nanoparticles were confirmed by UV–vis spectrophotometer, absorbance peaks at 285 nm. The copper oxide nanoparticles were analyzed with field emission-scanning electron microscope (FE-SEM), Fourier transform infrared (FT-IR) spectroscopy, dynamic light scattering (DLS) and X-ray diffraction (XRD) spectrum. The FE-SEM and DLS analyses exposed that copper oxide nanoparticles are spherical in shape with an average particle size of 577 nm. FT-IR spectral analysis elucidates the occurrence of biomolecules required for the reduction of copper oxide ions. Zeta potential studies showed that the surface charge of the formed nanoparticles was highly negative. The XRD pattern revealed that synthesized nanoparticles are crystalline in nature. Further, biological activities of the synthesized nanoparticles were confirmed based on its stable anti-cancer effects. The apoptotic effect of copper oxide nanoparticles is mediated by the generation of reactive oxygen species (ROS) involving the disruption of mitochondrial membrane potential (Δψm) in A549 cells. The observed characteristics and results obtained in our in vitro assays suggest that the copper nanoparticles might be a potential anticancer agent. - Highlights: • Biogenic synthesis of copper oxide nanoparticles by leaf extract of Ficus religiosa • Characterized via UV–vis, FT-IR, DLS, FE-SEM with EDAX and XRD • Protein may act as an encapsulating, reducing and stabilizing

  18. From antimicrobial to anticancer peptides. A review.

    Directory of Open Access Journals (Sweden)

    Diana eGaspar

    2013-10-01

    Full Text Available Antimicrobial peptides (AMPs are part of the innate immune defense mechanism of many organisms. Although AMPs have been essentially studied and developed as potential alternatives for fighting infectious diseases, their use as anticancer peptides (ACPs in cancer therapy either alone or in combination with other conventional drugs has been regarded as a therapeutic strategy to explore. As human cancer remains a cause of high morbidity and mortality worldwide, an urgent need of new, selective and more efficient drugs is evident. Even though ACPs are expected to be selective towards tumor cells without impairing the normal body physiological functions, the development of a selective ACP has been a challenge. It is not yet possible to predict antitumor activity based on ACPs structures. ACPs are unique molecules when compared to the actual chemotherapeutic arsenal available for cancer treatment and display a variety of modes of action which in some types of cancer seem to co-exist. Regardless the debate surrounding the definition of structure-activity relationships for ACPs, great effort has been invested in ACP design and the challenge of improving effective killing of tumor cells remains. As detailed studies on ACPs mechanisms of action are crucial for optimizing drug development, in this review we provide an overview of the literature concerning peptides’ structure, modes of action, selectivity and efficacy and also summarize some of the many ACPs studied and/or developed for targeting different solid and hematologic malignancies with special emphasis on the first group. Strategies described for drug development and for increasing peptide selectivity towards specific cells while reducing toxicity are also discussed.

  19. 靶向性抗癌治疗的纳米技术%Nanotechnology for targeted anticancer therapies

    Institute of Scientific and Technical Information of China (English)

    罗育林

    2005-01-01

    Although many anticancer therapies are used in clinic, few are tolerable for their side effects from killing of normal cells. Seeking measures to target anticancer agents to tumors or at least tumor-located organs has been one of the major tasks for researchers. Nanotechnology is greatly helpful for fulfilling this task. There are several ways to direct therapeutic agents carried by nanoparticles to tumor sites. This article focuses on the mechanisms,advantages and disadvantages of different targeting manners, understanding of which may be benefitial to researchers to develop specific targeted anticancer therapy.

  20. Synthesis and Biological Activity of Anticancer Ether Lipids That Are Specifically Released by Phospholipase A2 in Tumor Tissue

    DEFF Research Database (Denmark)

    Andresen, Thomas L.; Jensen, Simon Skøde; Madsen, Robert; Jørgensen, Kent

    2005-01-01

    The clinical use of anticancer lipids is severely limited by their ability to cause lysis of red blood cells prohibiting intravenous injection. Novel delivery systems are therefore required in order to develop anticancer ether lipids (AELs) into clinically useful anticancer drugs. In a recent...... synthesized AEL 1-6 were tested against three different cancer cell lines. It was found that the stereochemistry of the glycerol headgroup in AEL-2 and 3 has a dramatic effect on the cytotoxicity of the lipids. AEL 1-4 were furthermore evaluated for their ability to prevent phosphorylation of the apoptosis...

  1. PEPTIDE TARGETING OF PLATINUM ANTI-CANCER DRUGS

    OpenAIRE

    Ndinguri, Margaret W.; Solipuram, Rajasree; Gambrell, Robert P.; Aggarwal, Sita; Hansel, William; Hammer, Robert P.

    2009-01-01

    Besides various side effects caused by platinum anticancer drugs, they are not efficiently absorbed by the tumor cells. Two Pt-peptide conjugates; cyclic mPeg-CNGRC-Pt (7) and cyclic mPeg-CNGRC-Pten (8) bearing the Asn-Gly-Arg (NGR) targeting sequence, a malonoyl linker and low molecular weight miniPEG groups have been synthesized. The platinum ligand was attached to the peptide via the carboxylic end of the malonate group at the end of the peptide. The pegylated peptide is non toxic and high...

  2. Transportan 10 improves the anticancer activity of cisplatin.

    Science.gov (United States)

    Izabela, Rusiecka; Jarosław, Ruczyński; Magdalena, Alenowicz; Piotr, Rekowski; Ivan, Kocić

    2016-05-01

    The aim of this paper was to examine whether cell-penetrating peptides (CPPs) such as transportan 10 (TP10) or protein transduction domain (PTD4) may improve the anticancer activity of cisplatin (cPt). The complexes of TP10 or PTD4 with cPt were used in the experiments. They were carried out on two non-cancer (HEK293 (human embryonic kidney) and HEL299 (human embryo lung)) and two cancer (HeLa (human cervical cancer) and OS143B (human osteosarcoma 143B)) cell lines. Both complexes were tested (MTT assay) with respect to their anticancer or cytotoxic actions. TAMRA (fluorescent dye)-stained preparations were visualized in a fluorescence microscope. The long-term effect of TP10 + cPt and its components on non-cancer and cancer cell lines was observed in inverted phase contrast microscopy. In the MTT test (cell viability assay), the complex of TP10 + cPt produced a more potent effect on the cancer cell lines (HeLa, OS143B) in comparison to that observed after separate treatment with TP10 or cPt. At the same time, the action of the complex and its components was rather small on non-cancer cell lines. On the other hand, a complex of another CPP with cPt, i.e., PTD4 + cPt, was without a significant effect on the cancer cell line (OS143B). The images of the fluorescent microscopy showed TAMRA-TP10 or TAMRA-TP10 + cPt in the interior of the HeLa cells. In the case of TAMRA-PTD4 or TAMRA-PTD4 + cPt, only the first compound was found inside the cancer cell line. In contrast, none of the tested compounds gained access to the interior of the non-cancer cells (HEK293, HEL299). Long-term incubation with the TP10 + cPt (estimated by inverted phase contrast microscopy) lead to an enhanced action of the complex on cell viability (decrease in the number of cells and change in their morphology) as compared with that produced by each single agent. With regard to the tested CPPs, only TP10 improved the anticancer activity of cisplatin if both compounds were used in the form of a

  3. Anti-cancer Activities of Ginseng Extract Fermented with Phellinus linteus

    OpenAIRE

    Lee, Jong-Jin; Kwon, Ho-Kyun; Jung, In-Ho; Cho, Yong-Baik; Kim, Kyu-Joong; Kim, Jong-Lae

    2009-01-01

    In the present study, the anti-cancer effects of ginseng fermented with Phellinus linteus (GFPL) extract were examined through in vitro and in vivo assays. GFPL was produced by co-cultivating ginseng and Phellinus linteus together. Ginsenoside Rg3, Rh1 and Rh2 are important mediators of anti-angiogenesis and their levels in GFPL were enriched 24, 19 and 16 times, respectively, more than that of ginseng itself through the fermentation. GFPL exhibited distinct anti-cancer effects, including gro...

  4. Anticancer Effect of 5-Florouracil Combined with Extract of Rosa roxburghii Tratt on Human Endometrial Adenocarcinoma%刺梨提取物联合5-氟尿嘧啶抗人子宫内膜腺癌作用

    Institute of Scientific and Technical Information of China (English)

    戴支凯; 杨小生; 余丽梅

    2011-01-01

    Objective To investigate anticancer effects of 5-florouracil (5-FU) combined with CL, extract of Rosa roxburghii Tratt on human endometrial adenocarcinoma cell line (JEC). Methods JEC cells cultured in vitro in the logarithmic growth phase were seeded in the culture plate and divided into the control group (RPMI 1640), the positive group (10~4 mol/L 5-FU), the CL groups (at the dose of 0.01, 0.1, 1, 10, and 100 ug/mL), and the CL (0. 01, 0.1, 1, 10, and 100 ug/mL) combined with 5-FU groups. Effects of 5-FU combined with CL on JEC cell growth were drawn and measured by MTT and growth curves. Effects of CL combined with 5-FU on the JEC cell differentiation was analyzed by detecting the reduction capability of nitrobenzene thiocyanate (NBT) and lactate dehydrogenase (LDH) contents in the cultured medium. Effects of CL combined with 5-FU on the JEC cell apoptosis and cell proliferation cycle were detected by acridine orange (AO)/ethidium bromide (EB) fluorescent staining and flow cytometry (FCM). Results The proliferation inhibitory effect of CL combined with 5-FU on JEC cells was enhanced when compared with that of CL or 5-FU alone (P<0.05). The percentages of NBT positive JEC cells and apoptotic JEC cells increased in the 5-FU combined with CL groups when compared with 5-FU group or the CL group alone (P<0.05). The LDH concentration of the JEC cell culture supemate decreased in 5-FU combined with CL groups (P<0.05). Furthermore, the percentage of G0-G1 phase JEC cells treated by 5-FU combined with CL was higher than that of 5-FU or CL alone (P <0.05). Conclusion CL could enhance anticancer effects of 5-FU. Its mechanisms might be correlated with reinforcing the cytotoxicity of 5-FU, inducing cell differentiation and apoptosis, and inhibiting cell proliferation and division.%目的 探讨刺梨提取物(CL)联合5-氟尿嘧啶(5-florouracil,5-FU)的抗子宫内膜腺癌细胞株(JEC)作用.方法 将体外培养的指数生长期细胞接种于培

  5. Development of Platinum(iv) Complexes as Anticancer Prodrugs: the Story so Far

    Science.gov (United States)

    Wong, Daniel Yuan Qiang; Ang, Wee Han

    2012-06-01

    The serendipitous discovery of the antitumor properties of cisplatin by Barnett Rosenberg some forty years ago brought about a paradigm shift in the field of medicinal chemistry and challenged conventional thinking regarding the role of potentially toxic heavy metals in drugs. Platinum(II)-based anticancer drugs have since become some of the most effective and widely-used drugs in a clinician's arsenal and have saved countless lives. However, they are limited by high toxicity, severe side-effects and the incidence of drug resistance. In recent years, attention has shifted to stable platinum(IV) complexes as anticancer prodrugs. By exploiting the unique chemical and structural attributes of their scaffolds, these platinum(IV) prodrugs offer new strategies of targeting and killing cancer cells. This review summarizes the development of anticancer platinum(IV) prodrugs to date and some of the exciting strategies that utilise the platinum(IV) construct as targeted chemotherapeutic agents against cancer.

  6. Hyperthermia enhances the anticancer-drug induced cytotoxicity in hepatocellular carcinoma cell line SMMC-7721

    Institute of Scientific and Technical Information of China (English)

    Yang Yang; Baorui Liu; Xiaoping Qian

    2006-01-01

    Objective: Hyperthermia is an attractive addition to multidisciplinary approaches to clinical cancer treatment.The efficiency of hyperthermia depends on the elevation of the temperature and the duration of treatment. It has been reported that in vitro and in vivo hyperthermia enhanced the cytotoxic effect of certain anticancer drugs. However, this enhancement varies,depending on the drug used and the scheduling of treatments. Thus, the combination effect of chemotherapy and hyperthermia remains unclear. In this study, we aimed to investigate whether concurrent exposure of human hepatocellular carcinoma cells SMMC-7721 to chemotherapeutic agents andhypenhermia could increase anticancer effects. Methods: Two chemotherapeutic agents, cisplatin and hydroxycamptothecin, were applied. The MTT assay was performed to evaluate the growth inhibition of SMMC-7721 induced by anticancer drugs with and without hyperthermia. Flow cytometric analysis was used for the assessment of apoptosis after treatments. Results: The percentages of growth inhibition of SMMC-7721 induced by cisplatin (10 μg/ml) alone,hydroxycamptothecin (1 μg/ml) alone, hyperthermia alone, cisplatin and hyperthermia, hydroxycamptothecin and hyperthermia,were 20.77%, 13.65%, 32.46%, 62.76%, 71.89%, respectively. The percentages of apoptosis of five treatments are 5.56%,3.96%, 10.16%, 24.32%, 20.42%, respectively. Conclusion: While both hyperthermia and anticancer drugs can individually induce apoptosis and anti-proliferation effect, the combination of the two treatments induce significantly higher apoptosis and cytotoxicity than hyperthermia or anticancer drugs treatment alone. These data suggest a synergistic benefit when hyperthermia and anticancer drugs used concurrently.

  7. Anticancer Activity of Garcinia morella on T-Cell Murine Lymphoma Via Apoptotic Induction.

    Science.gov (United States)

    Choudhury, Bhaswati; Kandimalla, Raghuram; Bharali, Rupjyoti; Monisha, Javadi; Kunnumakara, Ajaikumar B; Kalita, Kasturi; Kotoky, Jibon

    2016-01-01

    Traditional knowledge (TK) based medicines have gained worldwide attention and presently the scientific community is focussing on proper pharmacological validation and identification of lead compounds for the treatment of various diseases. The North East region of India is the home of valuable traditional herbal remedies. Garcinia morella Desr. (Guttiferae) is one such medicinal plant used by traditional healers for the treatment of inflammatory disorders. The present study was aimed to evaluate the antioxidant and anticancer activity of methanol extracts of the leaf, bark and fruit of G. morella (GM) in different in vitro and in vivo experimental conditions. The results of this study showed that GM methanol extracts possessed in vitro antioxidant and anticancer properties, where the fruit extract (GF) showed maximum activity. The anticancer activity was further confirmed by the results of in vivo administration of GF (200 mg/kg) for ten days to Dalton's lymphoma (DLA) induced mice. GF extract significantly increased the mean survival time (MST) of the animals, decreased the tumor volume and restored the hematological and biochemical parameters. The present study for the first time reported the anticancer property of GF on DLA. Further from the experiments conducted to elucidate the mechanism of action of GF on DLA, it can be concluded that GF exerts its anticancer effect through induction of caspases and DNA fragmentation that ultimately leads to apoptosis. However, further experimentation is required to elucidate the active principle and validate these findings in various in vivo settings. PMID:26858645

  8. An Insight into the Anticancer Activities of Ru(II-Based Metallocompounds Using Docking Methods

    Directory of Open Access Journals (Sweden)

    Peter A. Ajibade

    2013-09-01

    Full Text Available Unlike organic molecules, reports on docking of metal complexes are very few; mainly due to the inadequacy of force fields in docking packages to appropriately characterize the metal atoms that consequentially hinder the rational design of metal-based drug complexes. In this study we have made used Molegro and Autodock to predict the anticancer activities of selected Ru(II complexes against twelve anticancer targets. We observed that introducing the quantum calculated atomic charges of the optimized geometries significantly improved the docking predictions of these anticancer metallocompounds. Despite several limitations in the docking of metal-based complexes, we obtained results that are highly correlated with the available experimental results. Most of our newly proposed metallocompounds are found theoretically to be better anticancer metallocompounds than all the experimentally proposed RAPTA complexes. An interesting features of a strong interactions of new modeled of metallocompounds against the two base edges of DNA strands suggest similar mechanisms of anticancer activities similar to that of cisplatin. There is possibility of covalent bonding between the metal center of the metallocompounds and the residues of the receptors DNA-1, DNA-2, HDAC7, HIS and RNR. However, the general results suggest the possibility of metals positioning the coordinated ligands in the right position for optimal receptor interactions and synergistic effects, rather than forming covalent bonds.

  9. Anticancer Activity of Garcinia morella on T-Cell Murine Lymphoma Via Apoptotic Induction

    Science.gov (United States)

    Choudhury, Bhaswati; Kandimalla, Raghuram; Bharali, Rupjyoti; Monisha, Javadi; Kunnumakara, Ajaikumar B.; Kalita, Kasturi; Kotoky, Jibon

    2016-01-01

    Traditional knowledge (TK) based medicines have gained worldwide attention and presently the scientific community is focussing on proper pharmacological validation and identification of lead compounds for the treatment of various diseases. The North East region of India is the home of valuable traditional herbal remedies. Garcinia morella Desr. (Guttiferae) is one such medicinal plant used by traditional healers for the treatment of inflammatory disorders. The present study was aimed to evaluate the antioxidant and anticancer activity of methanol extracts of the leaf, bark and fruit of G. morella (GM) in different in vitro and in vivo experimental conditions. The results of this study showed that GM methanol extracts possessed in vitro antioxidant and anticancer properties, where the fruit extract (GF) showed maximum activity. The anticancer activity was further confirmed by the results of in vivo administration of GF (200 mg/kg) for ten days to Dalton’s lymphoma (DLA) induced mice. GF extract significantly increased the mean survival time (MST) of the animals, decreased the tumor volume and restored the hematological and biochemical parameters. The present study for the first time reported the anticancer property of GF on DLA. Further from the experiments conducted to elucidate the mechanism of action of GF on DLA, it can be concluded that GF exerts its anticancer effect through induction of caspases and DNA fragmentation that ultimately leads to apoptosis. However, further experimentation is required to elucidate the active principle and validate these findings in various in vivo settings. PMID:26858645

  10. Novel walnut peptide–selenium hybrids with enhanced anticancer synergism: facile synthesis and mechanistic investigation of anticancer activity

    Directory of Open Access Journals (Sweden)

    Liao W

    2016-04-01

    Full Text Available Wenzhen Liao,1 Rong Zhang,1 Chenbo Dong,2 Zhiqiang Yu,3 Jiaoyan Ren11College of Light Industry and Food Sciences, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China; 2Civil and Environmental Engineering, Rice University, Houston, TX, USA; 3School of Pharmaceutical Science, Guangdong Provincial Key Laboratory of New Drug Screening, Southern Medical University, Guangzhou, Guangdong, People’s Republic of ChinaAbstract: This contribution reports a facile synthesis of degreased walnut peptides (WP1-functionalized selenium nanoparticles (SeNPs hybrids with enhanced anticancer activity and a detailed mechanistic evaluation of its superior anticancer activity. Structural and chemical characterizations proved that SeNPs are effectively capped with WP1 via physical absorption, resulting in a stable hybrid structure with an average diameter of 89.22 nm. A panel of selected human cancer cell lines demonstrated high susceptibility toward WP1-SeNPs and displayed significantly reduced proliferative behavior. The as-synthesized WP1-SeNPs exhibited excellent selectivity between cancer cells and normal cells. The targeted induction of apoptosis in human breast adenocarcinoma cells (MCF-7 was confirmed by the accumulation of arrested S-phase cells, nuclear condensation, and DNA breakage. Careful investigations revealed that an extrinsic apoptotic pathway can be attributed to the cell apoptosis and the same was confirmed by activation of the Fas-associated with death domain protein and caspases 3, 8, and 9. In addition, it was also understood that intrinsic apoptotic pathways including reactive oxygen species generation, as well as the reduction in mitochondrial membrane potential, are also involved in the WP1-SeNP-induced apoptosis. This suggested the involvement of multiple apoptosis pathways in the anticancer activity. Our results indicated that WP1-SeNP hybrids with Se core encapsulated in a WP1 shell could be a highly

  11. Arene ruthenium complexes as anticancer agents

    OpenAIRE

    Süss-Fink, Georg

    2012-01-01

    Neutral or cationic arene ruthenium complexes providing both hydrophilic as well as hydrophobic properties due to the robustness of the ruthenium–arene unit hold a high potential for the development of metal-based anticancer drugs. Mononuclear arene ruthenium complexes containing P- or N-donor ligands or N,N-, N,O- or O,O-chelating ligands, dinuclear arene ruthenium systems with adjustable organic linkers, trinuclear arene ruthenium clusters containing an oxo cap, tetranuclear arene ruthenium...

  12. Therapeutic aptamers: developmental potential as anticancer drugs

    OpenAIRE

    Lee, Ji Won; Kim, Hyun Jung; Heo, Kyun

    2015-01-01

    Aptamers, composed of single-stranded DNA or RNA oligonucleotides that interact with target molecules through a specific three-dimensional structure, are selected from pools of combinatorial oligonucleotide libraries. With their high specificity and affinity for target proteins, ease of synthesis and modification, and low immunogenicity and toxicity, aptamers are considered to be attractive molecules for development as anticancer therapeutics. Two aptamers - one targeting nucleolin and a seco...

  13. Are isothiocyanates potential anti-cancer drugs?

    Institute of Scientific and Technical Information of China (English)

    Xiang WU; Qing-hua ZHOU; Ke XU

    2009-01-01

    Isothiocyanates are naturally occurring small molecules that are formed from glucosinolate precursors of cruciferous vegetables. Many isothiocyanates, both natural and synthetic, display anticarcinogenic activity because they reduce activation of carcinogens and increase their detoxification. Recent studies show that they exhibit anti-tumor activity by affecting multiple pathways including apoptosis, MAPK signaling, oxidative stress, and cell cycle progression. This review summarizes the current knowledge on isothiocyanates and focuses on their role as potential anti-cancer agents.

  14. ANTICANCER POTENTIAL OF BAMBUSA BAMBOS LEAF EXTRACTS

    OpenAIRE

    Muneerudeen J; Himanshu Joshi; Gururaja M.P.; Devi Swapna PV; Lekshmi P; Jipnomon J; C S Shastry

    2013-01-01

    Anti-cancer activities of chloroform and hydro-alcohol leaf extracts of Bambusa bambos was evaluated in vitro using Dalton’s Lymphoma Ascites (DLA) and Ehrlich’s Ascites Carcinoma (EAC) cell lines by Trypan blue dye exclusion method. The chloroform extract exhibited better activity compared to hydro-alcohol extract. Further hemolytic activities of both the extracts were carried out to measure the extent of damage to normal red blood cell membranes. The findings suggested that both the extract...

  15. Polymer anticancer drugs with peptide targeting

    Czech Academy of Sciences Publication Activity Database

    Studenovský, Martin; Pola, Robert; Pechar, Michal; Ulbrich, Karel; Hovorka, Ondřej

    Long Beach : Controlled Release Society, 2007, 771/1-771/2. [Annual Meeting and Exposition of the Controlled Release Society /34./. Long Beach (US), 07.07.2007-11.07.2007] R&D Projects: GA ČR GA204/05/2255 Institutional research plan: CEZ:AV0Z40500505; CEZ:AV0Z50200510 Keywords : angiogenesis * anticancer agents * conjugates * HPMA copolymers Subject RIV: CE - Biochemistry http://www.controlledreleasesociety.org/meeting/program/pdfs/ProgramBook.pdf

  16. Bacteria under SOS evolve anticancer phenotypes

    OpenAIRE

    Weitao Tao; Dallo Shatha F

    2010-01-01

    Abstract Background The anticancer drugs, such as DNA replication inhibitors, stimulate bacterial adhesion and induce the bacterial SOS response. As a variety of bacterial mutants can be generated during SOS, novel phenotypes are likely to be selected under the drug pressure. Presentation of the hypothesis Bacteria growing with cancer cells in the presence of the replication inhibitors undergo the SOS response and evolve advantageous phenotypes for the bacteria to invade the cancer cells in o...

  17. From antimicrobial to anticancer peptides. A review.

    OpenAIRE

    Diana eGaspar; A. Salomé eVeiga; Miguel A.R.B. eCastanho

    2013-01-01

    Antimicrobial peptides (AMPs) are part of the innate immune defense mechanism of many organisms. Although AMPs have been essentially studied and developed as potential alternatives for fighting infectious diseases, their use as anticancer peptides (ACPs) in cancer therapy either alone or in combination with other conventional drugs has been regarded as a therapeutic strategy to explore. As human cancer remains a cause of high morbidity and mortality worldwide, an urgent need of new, selective...

  18. Some medicinal plants as natural anticancer agents

    OpenAIRE

    Govind Pandey; S Madhuri

    2009-01-01

    India is the largest producer of medicinal plants and is rightly called the "Botanical garden of the World". The medicinal plants, besides having natural therapeutic values against various diseases, also provide high quality of food and raw materials for livelihood. Considerable works have been done on these plants to treat cancer, and some plant products have been marketed as anticancer drugs, based on the traditional uses and scientific reports. These plants may promote host resistance agai...

  19. Phytochemistry and Anticancer Potential of Notoginseng.

    Science.gov (United States)

    Wang, Chong-Zhi; Anderson, Samantha; Yuan, Chun-Su

    2016-01-01

    Asian ginseng, American ginseng, and notoginseng are three major species in the ginseng family. Notoginseng is a Chinese herbal medicine with a long history of use in many Oriental countries. This botanical has a distinct ginsenoside profile compared to other ginseng herbs. As a saponin-rich plant, notoginseng could be a good candidate for cancer chemoprevention. However, to date, only relatively limited anticancer studies have been conducted on notoginseng. In this paper, after reviewing its anticancer data, phytochemical isolation and analysis of notoginseng is presented in comparison with Asian ginseng and American ginseng. Over 80 dammarane saponins have been isolated and elucidated from different plant parts of notoginseng, most of them belonging to protopanaxadiol or protopanaxatriol groups. The role of the enteric microbiome in mediating notoginseng metabolism, bioavailability, and pharmacological actions are discussed. Emphasis has been placed on the identification and isolation of enteric microbiome-generated notoginseng metabolites. Future investigations should provide key insights into notoginseng's bioactive metabolites as clinically valuable anticancer compounds. PMID:26916912

  20. AlgiMatrix™ based 3D cell culture system as an in-vitro tumor model for anticancer studies.

    Directory of Open Access Journals (Sweden)

    Chandraiah Godugu

    Full Text Available BACKGROUND: Three-dimensional (3D in-vitro cultures are recognized for recapitulating the physiological microenvironment and exhibiting high concordance with in-vivo conditions. Taking the advantages of 3D culture, we have developed the in-vitro tumor model for anticancer drug screening. METHODS: Cancer cells grown in 6 and 96 well AlgiMatrix™ scaffolds resulted in the formation of multicellular spheroids in the size range of 100-300 µm. Spheroids were grown in two weeks in cultures without compromising the growth characteristics. Different marketed anticancer drugs were screened by incubating them for 24 h at 7, 9 and 11 days in 3D cultures and cytotoxicity was measured by AlamarBlue® assay. Effectiveness of anticancer drug treatments were measured based on spheroid number and size distribution. Evaluation of apoptotic and anti-apoptotic markers was done by immunohistochemistry and RT-PCR. The 3D results were compared with the conventional 2D monolayer cultures. Cellular uptake studies for drug (Doxorubicin and nanoparticle (NLC were done using spheroids. RESULTS: IC(50 values for anticancer drugs were significantly higher in AlgiMatrix™ systems compared to 2D culture models. The cleaved caspase-3 expression was significantly decreased (2.09 and 2.47 folds respectively for 5-Fluorouracil and Camptothecin in H460 spheroid cultures compared to 2D culture system. The cytotoxicity, spheroid size distribution, immunohistochemistry, RT-PCR and nanoparticle penetration data suggested that in vitro tumor models show higher resistance to anticancer drugs and supporting the fact that 3D culture is a better model for the cytotoxic evaluation of anticancer drugs in vitro. CONCLUSION: The results from our studies are useful to develop a high throughput in vitro tumor model to study the effect of various anticancer agents and various molecular pathways affected by the anticancer drugs and formulations.

  1. T-oligo as an anticancer agent in colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wojdyla, Luke; Stone, Amanda L. [Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, IL (United States); Sethakorn, Nan [Department of Medicine, University of Chicago, Chicago, IL (United States); Uppada, Srijayaprakash B.; Devito, Joseph T. [Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, IL (United States); Bissonnette, Marc [Department of Medicine, University of Chicago, Chicago, IL (United States); Puri, Neelu, E-mail: neelupur@uic.edu [Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, IL (United States)

    2014-04-04

    Highlights: • T-oligo induces cell cycle arrest, senescence, apoptosis, and differentiation in CRC. • Treatment with T-oligo downregulates telomere-associated proteins. • T-oligo combined with an EGFR-TKI additively inhibits cellular proliferation. • T-oligo has potential as an effective therapeutic agent for CRC. - Abstract: In the United States, there will be an estimated 96,830 new cases of colorectal cancer (CRC) and 50,310 deaths in 2014. CRC is often detected at late stages of the disease, at which point there is no effective chemotherapy. Thus, there is an urgent need for effective novel therapies that have minimal effects on normal cells. T-oligo, an oligonucleotide homologous to the 3′-telomere overhang, induces potent DNA damage responses in multiple malignant cell types, however, its efficacy in CRC has not been studied. This is the first investigation demonstrating T-oligo-induced anticancer effects in two CRC cell lines, HT-29 and LoVo, which are highly resistant to conventional chemotherapies. In this investigation, we show that T-oligo may mediate its DNA damage responses through the p53/p73 pathway, thereby inhibiting cellular proliferation and inducing apoptosis or senescence. Additionally, upregulation of downstream DNA damage response proteins, including E2F1, p53 or p73, was observed. In LoVo cells, T-oligo induced senescence, decreased clonogenicity, and increased expression of senescence associated proteins p21, p27, and p53. In addition, downregulation of POT1 and TRF2, two components of the shelterin protein complex which protects telomeric ends, was observed. Moreover, we studied the antiproliferative effects of T-oligo in combination with an EGFR tyrosine kinase inhibitor, Gefitinib, which resulted in an additive inhibitory effect on cellular proliferation. Collectively, these data provide evidence that T-oligo alone, or in combination with other molecularly targeted therapies, has potential as an anti-cancer agent in CRC.

  2. Genetic Interactions of STAT3 and Anticancer Drug Development

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Bingliang [Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030 (United States)

    2014-03-06

    Signal transducer and activator of transcription 3 (STAT3) plays critical roles in tumorigenesis and malignant evolution and has been intensively studied as a therapeutic target for cancer. A number of STAT3 inhibitors have been evaluated for their antitumor activity in vitro and in vivo in experimental tumor models and several approved therapeutic agents have been reported to function as STAT3 inhibitors. Nevertheless, most STAT3 inhibitors have yet to be translated to clinical evaluation for cancer treatment, presumably because of pharmacokinetic, efficacy, and safety issues. In fact, a major cause of failure of anticancer drug development is lack of efficacy. Genetic interactions among various cancer-related pathways often provide redundant input from parallel and/or cooperative pathways that drives and maintains survival environments for cancer cells, leading to low efficacy of single-target agents. Exploiting genetic interactions of STAT3 with other cancer-related pathways may provide molecular insight into mechanisms of cancer resistance to pathway-targeted therapies and strategies for development of more effective anticancer agents and treatment regimens. This review focuses on functional regulation of STAT3 activity; possible interactions of the STAT3, RAS, epidermal growth factor receptor, and reduction-oxidation pathways; and molecular mechanisms that modulate therapeutic efficacies of STAT3 inhibitors.

  3. Tristetraprolin: a novel mediator of the anticancer properties of resveratrol.

    Science.gov (United States)

    Li, C; Tang, C; He, G

    2016-01-01

    Resveratrol is a natural compound that exhibits anticancer properties. Previous studies have proved that it can inhibit the proliferation of breast cancer cell lines and upregulate some cytokines such as cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF). The initiation and progression of cancer are associated with the abnormal expression of multiple cytokines. Tristetraprolin (TTP), an mRNA-binding protein, is one of the key proteins that participate in regulating cytokine expression. Two different proliferation assays on MCF-7 cells showed that the cell proliferation rate significantly reduced following treatment with resveratrol. Most importantly, we found that resveratrol promoted TTP expression at both the mRNA and protein level in a dose- and time-dependent manner. In addition, the expression of COX-2 and VEGF were significantly suppressed by resveratrol while that of inducible nitric oxide synthase (iNOS) was upregulated. Lastly, the effects of resveratrol on both MCF-7 proliferation and expression of COX-2, VEGF, and iNOS were significantly inhibited by TTP knockdown, indicating that TTP mediates the anticancer properties of resveratrol. In summary, we conclude that resveratrol inhibits the proliferation of MCF-7 cells by TTP upregulation, which is associated with downregulation of COX-2 and VEGF and upregulation of iNOS. PMID:27323060

  4. Lymphatic Targeting of Nanosystems for Anticancer Drug Therapy.

    Science.gov (United States)

    Abellan-Pose, Raquel; Csaba, Noemi; Alonso, Maria Jose

    2016-01-01

    The lymphatic system represents a major route of dissemination in metastatic cancer. Given the lack of selectivity of conventional chemotherapy to prevent lymphatic metastasis, in the last years there has been a growing interest in the development of nanocarriers showing lymphotropic characteristics. The goal of this lymphotargeting strategy is to facilitate the delivery of anticancer drugs to the lymph node-resident cancer cells, thereby enhancing the effectiveness of the anti-cancer therapies. This article focuses on the nanosystems described so far for the active or passive targeting of oncological drugs to the lymphatic circulation. To understand the design and performance of these nanosystems, we will discuss first the physiology of the lymphatic system and how physiopathological changes associated to tumor growth influence the biodistribution of nanocarriers. Second, we provide evidence on how the tailoring of the physicochemical characteristics of nanosystems, i.e. particle size, surface charge and hydrophilicity, allows the modulation of their access to the lymphatic circulation. Finally, we provide an overview of the relationship between the biodistribution and antimetastatic activity of the nanocarriers loaded with oncological drugs, and illustrate the most promising active targeting approaches investigated so far. PMID:26675222

  5. "Ziziphus jujuba": A red fruit with promising anticancer activities

    Directory of Open Access Journals (Sweden)

    Zoya Tahergorabi

    2015-01-01

    Full Text Available Ziziphus jujuba Mill. (Z. jujuba is a traditional herb with a long history of use for nutrition and the treatment of a broad spectrum of diseases. It grows mostly in South and East Asia, as well as in Australia and Europe. Mounting evidence shows the health benefits of Z. jujuba, including anticancer, anti-inflammation, antiobesity, antioxidant, and hepato- and gastrointestinal protective properties, which are due to its bioactive compounds. Chemotherapy, such as with cis-diamminedichloroplatinium (CDDP, cisplatin and its derivatives, is widely used in cancer treatment. It is an effective treatment for human cancers,  including ovarian cancer; however, drug resistance is a major obstacle to successful treatment. A better understanding of the mechanisms and strategies for overcoming chemoresistance can greatly improve therapeutic outcomes for patients. In this review article, the bioactive compounds present in Z. jujuba are explained. The high prevalence of many different cancers worldwide has recently attracted the attention of many researchers. This is why our research group focused on studying the anticancer activity of Z. jujuba as well as its impact on chemoresistance both in vivo and in vitro. We hope that these studies can lead to a promising future for cancer patients.

  6. Genetic Interactions of STAT3 and Anticancer Drug Development

    International Nuclear Information System (INIS)

    Signal transducer and activator of transcription 3 (STAT3) plays critical roles in tumorigenesis and malignant evolution and has been intensively studied as a therapeutic target for cancer. A number of STAT3 inhibitors have been evaluated for their antitumor activity in vitro and in vivo in experimental tumor models and several approved therapeutic agents have been reported to function as STAT3 inhibitors. Nevertheless, most STAT3 inhibitors have yet to be translated to clinical evaluation for cancer treatment, presumably because of pharmacokinetic, efficacy, and safety issues. In fact, a major cause of failure of anticancer drug development is lack of efficacy. Genetic interactions among various cancer-related pathways often provide redundant input from parallel and/or cooperative pathways that drives and maintains survival environments for cancer cells, leading to low efficacy of single-target agents. Exploiting genetic interactions of STAT3 with other cancer-related pathways may provide molecular insight into mechanisms of cancer resistance to pathway-targeted therapies and strategies for development of more effective anticancer agents and treatment regimens. This review focuses on functional regulation of STAT3 activity; possible interactions of the STAT3, RAS, epidermal growth factor receptor, and reduction-oxidation pathways; and molecular mechanisms that modulate therapeutic efficacies of STAT3 inhibitors

  7. The promising alliance of anti-cancer electrochemotherapy with immunotherapy.

    Science.gov (United States)

    Calvet, Christophe Y; Mir, Lluis M

    2016-06-01

    Anti-tumor electrochemotherapy, which consists in increasing anti-cancer drug uptake by means of electroporation, is now implanted in about 140 cancer treatment centers in Europe. Its use is supported by the English National Institute for Health and Care Excellence for the palliative treatment of skin metastases, and about 13,000 cancer patients were treated by this technology by the end of 2015. Efforts are now focused on turning this local anti-tumor treatment into a systemic one. Electrogenetherapy, that is the electroporation-mediated transfer of therapeutic genes, is currently under clinical evaluation and has brought excitement to enlarge the anti-cancer armamentarium. Among the promising electrogenetherapy strategies, DNA vaccination and cytokine-based immunotherapy aim at stimulating anti-tumor immunity. We review here the interests and state of development of both electrochemotherapy and electrogenetherapy. We then emphasize the potent beneficial outcome of the combination of electrochemotherapy with immunotherapy, such as immune checkpoint inhibitors or strategies based on electrogenetherapy, to simultaneously achieve excellent local debulking anti-tumor responses and systemic anti-metastatic effects. PMID:26993326

  8. Anticancer and Antioxidant Activity of Bread Enriched with Broccoli Sprouts

    Directory of Open Access Journals (Sweden)

    Urszula Gawlik-Dziki

    2014-01-01

    Full Text Available This study is focused on antioxidant and anticancer capacity of bread enriched with broccoli sprouts (BS in the light of their potential bioaccessibility and bioavailability. Generally, bread supplementation elevated antioxidant potential of product (both nonenzymatic and enzymatic antioxidant capacities; however, the increase was not correlated with the percent of BS. A replacement up to 2% of BS gives satisfactory overall consumers acceptability and desirable elevation of antioxidant potential. High activity was especially found for extracts obtained after simulated digestion, which allows assuming their protective effect for upper gastrointestinal tract; thus, the anticancer activity against human stomach cancer cells (AGS was evaluated. A prominent cytostatic response paralleled by the inhibition of AGS motility in the presence of potentially mastication-extractable phytochemicals indicates that phenolic compounds of BS retain their biological activity in bread. Importantly, the efficient phenolics concentration was about 12 μM for buffer extract, 13 μM for extracts after digestion in vitro, and 7 μM for extract after absorption in vitro. Our data confirm chemopreventive potential of bread enriched with BS and indicate that BS comprise valuable food supplement for stomach cancer chemoprevention.

  9. A Systematic Review of the Anticancer Properties of Compounds Isolated from Licorice (Gancao).

    Science.gov (United States)

    Tang, Zheng-Hai; Li, Ting; Tong, Yun-Guang; Chen, Xiao-Jia; Chen, Xiu-Ping; Wang, Yi-Tao; Lu, Jin-Jian

    2015-12-01

    Licorice (Gancao in Chinese) has been used worldwide as a botanical source in medicine and as a sweetening agent in food products for thousands of years. Triterpene saponins and flavonoids are its main ingredients that exhibit a variety of biological activities, including hepatoprotective, antiulcer, anti-inflammatory, antiviral and anticancer effects among others. This review attempts to summarize the current knowledge on the anticancer properties and mechanisms of the compounds isolated from licorice and obtain new insights for further research and development of licorice. A broad spectrum of in vitro and in vivo studies have recently demonstrated that the mixed extracts and purified compounds from licorice exhibit evident anticancer properties by inhibition of proliferation, induction of cell cycle arrest, apoptosis, autophagy, differentiation, suppression of metastasis, angiogenesis, and sensitization of chemotherapy or radiotherapy. A combined treatment of licorice compounds and clinical chemotherapy drugs remarkably enhances anticancer effects and reduces the side effects of chemotherapeutics. Furthermore, glycyrrhizic acid and glycyrrhetinic acid in licorice have been indicated to present obvious liver-targeting effects in targeted drug delivery systems for hepatocellular carcinoma treatment. PMID:26695708

  10. Targeting aerobic glycolysis: 3-bromopyruvate as a promising anticancer drug.

    Science.gov (United States)

    Cardaci, Simone; Desideri, Enrico; Ciriolo, Maria Rosa

    2012-02-01

    The Warburg effect refers to the phenomenon whereby cancer cells avidly take up glucose and produce lactic acid under aerobic conditions. Although the molecular mechanisms underlying tumor reliance on glycolysis remains not completely clear, its inhibition opens feasible therapeutic windows for cancer treatment. Indeed, several small molecules have emerged by combinatorial studies exhibiting promising anticancer activity both in vitro and in vivo, as a single agent or in combination with other therapeutic modalities. Therefore, besides reviewing the alterations of glycolysis that occur with malignant transformation, this manuscript aims at recapitulating the most effective pharmacological therapeutics of its targeting. In particular, we describe the principal mechanisms of action and the main targets of 3-bromopyruvate, an alkylating agent with impressive antitumor effects in several models of animal tumors. Moreover, we discuss the chemo-potentiating strategies that would make unparalleled the putative therapeutic efficacy of its use in clinical settings. PMID:22328057

  11. Anticancer activity of Cynodon dactylon and Oxalis corniculata on Hep2 cell line.

    Science.gov (United States)

    Salahuddin, H; Mansoor, Q; Batool, R; Farooqi, A A; Mahmood, T; Ismail, M

    2016-01-01

    Bioactive chemicals isolated from plants have attracted considerable attention over the years and overwhelmingly increasing laboratory findings are emphasizing on tumor suppressing properties of these natural agents in genetically and chemically induced animal carcinogenesis models. We studied in vitro anticancer activity of organic extracts of Cynodon dactylon and Oxalis corniculata on Hep2 cell line and it was compared with normal human corneal epithelial cells (HCEC) by using MTT assay. Real Time PCR was conducted for p53 and PTEN genes in treated cancer cell line. DNA fragmentation assay was also carried out to note DNA damaging effects of the extracts. The minimally effective concentration of ethanolic extract of Cynodon dactylon and methanolic extract of Oxalis corniculata that was nontoxic to HCEC but toxic to Hep2 was recorded (IC50) at a concentration of 0.042mg/ml (49.48 % cell death) and 0.048mg/ml (47.93% cell death) respectively, which was comparable to the positive control. Our results indicated dose dependent increase in cell death. P53 and PTEN did not show significant increase in treated cell line. Moreover, DNA damaging effects were also not detected in treated cancer cell line. Anticancer activity of these plants on the cancer cell line showed the presence of anticancer components which should be characterized to be used as anticancer therapy. PMID:27188871

  12. Current situation and future usage of anticancer drug databases.

    Science.gov (United States)

    Wang, Hongzhi; Yin, Yuanyuan; Wang, Peiqi; Xiong, Chenyu; Huang, Lingyu; Li, Sijia; Li, Xinyi; Fu, Leilei

    2016-07-01

    Cancer is a deadly disease with increasing incidence and mortality rates and affects the life quality of millions of people per year. The past 15 years have witnessed the rapid development of targeted therapy for cancer treatment, with numerous anticancer drugs, drug targets and related gene mutations been identified. The demand for better anticancer drugs and the advances in database technologies have propelled the development of databases related to anticancer drugs. These databases provide systematic collections of integrative information either directly on anticancer drugs or on a specific type of anticancer drugs with their own emphases on different aspects, such as drug-target interactions, the relationship between mutations in drug targets and drug resistance/sensitivity, drug-drug interactions, natural products with anticancer activity, anticancer peptides, synthetic lethality pairs and histone deacetylase inhibitors. We focus on a holistic view of the current situation and future usage of databases related to anticancer drugs and further discuss their strengths and weaknesses, in the hope of facilitating the discovery of new anticancer drugs with better clinical outcomes. PMID:27193464

  13. Hydrofocusing Bioreactor Produces Anti-Cancer Alkaloids

    Science.gov (United States)

    Gonda, Steve R.; Valluri, Jagan V.

    2011-01-01

    microgravitation of an HFB do not need to maintain the same surface forces as in normal Earth gravitation, they can divert more energy sources to growth and differentiation and, perhaps, to biosynthesis of greater quantities of desired medicinal compounds. Because one can adjust the HFB to vary effective gravitation, one can also test the effects of intermediate levels of gravitation on biosynthesis of various products. The potential utility of this methodology for producing drugs was demonstrated in experiments in which sandalwood and Madagascar periwinkle cells were grown in an HFB. The conditions in the HFB were chosen to induce the cells to form into aggregate cultures that produced anti-cancer indole alkaloids in amounts greater than do comparable numbers of cells of the same species cultured according to previously known methodologies. The observations made in these experiments were interpreted as suggesting that the aggregation of the cells might be responsible for the enhancement of production of alkaloids.

  14. 钝齿棒杆菌argR基因缺失株构建及其缺失对精氨酸生物合成途径相关基因转录水平的影响%Construction of Corynebacterium crenatum AS 1.542△argR and analysis of transcriptional levels of the related genes of arginine biosynthetic pathway

    Institute of Scientific and Technical Information of China (English)

    陈雪岚; 汤立; 焦海涛; 徐峰; 熊勇华

    2013-01-01

    [Objective] ArgR, coded by the argR gene from Corynebacterium crenatum AS 1. 542, acts as a negative regulator in arginine biosynthetic pathway. However, the effect of argR on transcriptional levels of the related biosynthetic genes has not been reported. Here, we constructed a deletion mutant of argR gene; C. Crenatum AS 1.542 △argR using marker-less knockout technology, and compared the changes of transcriptional levels of the arginine biosynthetic genes between the mutant strain and the wild-type strain. [Methods] We used marker-less knockout technology to construct C. Crenatum AS 1. 542△argR and analyzed the changes of the relate genes at the transcriptional level using real-time fluorescence quantitative PCR. [Results] C. Crenatum AS 1. 542△argR was successfully obtained and the transcriptional level of arginine biosynthetic genes in this mutant increased significantly with an average of about 162. 1 folds. [Conclusion] The arginine biosynthetic genes in C. Crenatum are clearly controlled by the negative regulator ArgR. However, the deletion of this regulator does not result in a clear change in arginine production in the bacteria.%[目的]钝齿棒杆菌AS 1.542中argR基因编码的蛋白ArgR在精氨酸生物合成途径中扮演负调控的角色,但其对相关基因在转录水平的影响还未见报道.因此,本课题组构建了钝齿棒杆菌argR基因缺失株,并在转录水平上比较野生株与缺失株精氨酸生物合成途径相关基因的变化.[方法]采用无痕敲除的方法构建了钝齿棒杆菌argR基因缺失株,并采用荧光定量PCR方法分析缺失株和野生株精氨酸生物合成途径相关基因在转录水平的变化.[结果]利用pK18mobsacB质粒中蔗糖致死基因sacB反向筛选标记及PCR方法成功筛选到钝齿棒杆菌argR基因缺失株;荧光定量PCR结果表明,argR基因缺失株精氨酸生物合成途径中相关基因在转录水平获得大量提高,平均约上调162.13倍.[结论]

  15. Plant Phenolics: Extraction, Analysis and Their Antioxidant and Anticancer Properties

    Directory of Open Access Journals (Sweden)

    Jin Dai

    2010-10-01

    Full Text Available Phenolics are broadly distributed in the plant kingdom and are the most abundant secondary metabolites of plants. Plant polyphenols have drawn increasing attention due to their potent antioxidant properties and their marked effects in the prevention of various oxidative stress associated diseases such as cancer. In the last few years, the identification and development of phenolic compounds or extracts from different plants has become a major area of health- and medical-related research. This review provides an updated and comprehensive overview on phenolic extraction, purification, analysis and quantification as well as their antioxidant properties. Furthermore, the anticancer effects of phenolics in-vitro and in-vivo animal models are viewed, including recent human intervention studies. Finally, possible mechanisms of action involving antioxidant and pro-oxidant activity as well as interference with cellular functions are discussed.

  16. ANTICANCER POTENTIAL OF BAMBUSA BAMBOS LEAF EXTRACTS

    Directory of Open Access Journals (Sweden)

    Muneerudeen J

    2013-04-01

    Full Text Available Anti-cancer activities of chloroform and hydro-alcohol leaf extracts of Bambusa bambos was evaluated in vitro using Dalton’s Lymphoma Ascites (DLA and Ehrlich’s Ascites Carcinoma (EAC cell lines by Trypan blue dye exclusion method. The chloroform extract exhibited better activity compared to hydro-alcohol extract. Further hemolytic activities of both the extracts were carried out to measure the extent of damage to normal red blood cell membranes. The findings suggested that both the extracts produced no signs of hemolysis indicating that the extracts are not toxic to normal erythrocytes.

  17. Impact of Apparent Antagonism of Estrogen Receptor β by Fulvestrant on Anticancer Activity of 2-Methoxyestradiol.

    Science.gov (United States)

    Gorska, Magdalena; Wyszkowska, Roksana Maja; Kuban-Jankowska, Alicja; Wozniak, Michal

    2016-05-01

    Osteosarcoma is one of the most malignant bone tumors of childhood and adolescence. Interestingly, the presence of estrogen receptors α and β has been reported in human bone cells, including osteosarcoma. Thus, inhibitors of estrogens such as fulvestrant, are considered candidates for novel endocrine therapy in treatment of osteosarcoma. Another anticancer agent that seems to be very effective in treatment of osteosarcoma is a derivative of 17β-estradiol, 2-methoxyestradiol. The aim of this study was to determine the anticancer activities of pure anti-estrogen, fulvestrant and combined treatment of fulvestrant and 2-methoxyestradiol towards highly metastatic osteosarcoma 143B cells. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay was used in order to determine the antiproliferative potential of the compounds, and western blotting for estrogen receptors α and β. Flow cytometry was used in order to determine induction of cell death, cell-cycle arrest, mitochondrial depolarization, and DNA damage. Herein, we showed that fulvestrant has anticancer activity only at high concentrations. We were able to find and expression of estrogen receptor β, while we did not detect estrogen receptor α in osteosarcoma 143B cells. Moreover, fulvestrant down-regulated the expression of estrogen receptor β, and this effect was reversed by 2-methoxyestradiol. Thus, the obtained data suggest that 2-methoxyestradiol may exert part of its anticancer activity through modulation of expression of estrogen receptor β. PMID:27127126

  18. Anticancer activity of Ficus religiosa engineered copper oxide nanoparticles.

    Science.gov (United States)

    Sankar, Renu; Maheswari, Ramasamy; Karthik, Selvaraju; Shivashangari, Kanchi Subramanian; Ravikumar, Vilwanathan

    2014-11-01

    The design, synthesis, characterization and application of biologically synthesized nanomaterials have become a vital branch of nanotechnology. There is a budding need to develop a method for environmentally benign metal nanoparticle synthesis, that do not use toxic chemicals in the synthesis protocols to avoid adverse effects in medical applications. Here, it is a report on an eco-friendly process for rapid synthesis of copper oxide nanoparticles using Ficus religiosa leaf extract as reducing and protecting agent. The synthesized copper oxide nanoparticles were confirmed by UV-vis spectrophotometer, absorbance peaks at 285 nm. The copper oxide nanoparticles were analyzed with field emission-scanning electron microscope (FE-SEM), Fourier transform infrared (FT-IR) spectroscopy, dynamic light scattering (DLS) and X-ray diffraction (XRD) spectrum. The FE-SEM and DLS analyses exposed that copper oxide nanoparticles are spherical in shape with an average particle size of 577 nm. FT-IR spectral analysis elucidates the occurrence of biomolecules required for the reduction of copper oxide ions. Zeta potential studies showed that the surface charge of the formed nanoparticles was highly negative. The XRD pattern revealed that synthesized nanoparticles are crystalline in nature. Further, biological activities of the synthesized nanoparticles were confirmed based on its stable anti-cancer effects. The apoptotic effect of copper oxide nanoparticles is mediated by the generation of reactive oxygen species (ROS) involving the disruption of mitochondrial membrane potential (Δψm) in A549 cells. The observed characteristics and results obtained in our in vitro assays suggest that the copper nanoparticles might be a potential anticancer agent. PMID:25280701

  19. Antioxidant, antimicrobial and anticancer activity of the lichens Cladonia furcata, Lecanora atra and Lecanora muralis

    Directory of Open Access Journals (Sweden)

    Stanojković Tatjana P

    2011-10-01

    Full Text Available Abstract Background The aim of this study is to investigate in vitro antioxidant, antimicrobial and anticancer activity of the acetone extracts of the lichens Cladonia furcata, Lecanora atra and Lecanora muralis. Methods Antioxidant activity was evaluated by five separate methods: free radical scavenging, superoxide anion radical scavenging, reducing power, determination of total phenolic compounds and determination of total flavonoid content. The antimicrobial activity was estimated by determination of the minimal inhibitory concentration by the broth microdilution method against six species of bacteria and ten species of fungi. Anticancer activity was tested against FemX (human melanoma and LS174 (human colon carcinoma cell lines using MTT method. Results Of the lichens tested, Lecanora atra had largest free radical scavenging activity (94.7% inhibition, which was greater than the standard antioxidants. Moreover, the tested extracts had effective reducing power and superoxide anion radical scavenging. The strong relationships between total phenolic and flavonoid contents and the antioxidant effect of tested extracts were observed. Extract of Cladonia furcata was the most active antimicrobial agent with minimum inhibitory concentration values ranging from 0.78 to 25 mg/mL. All extracts were found to be strong anticancer activity toward both cell lines with IC50 values ranging from 8.51 to 40.22 μg/mL. Conclusions The present study shows that tested lichen extracts demonstrated a strong antioxidant, antimicrobial and anticancer effects. That suggest that lichens may be used as as possible natural antioxidant, antimicrobial and anticancer agents to control various human, animal and plant diseases.

  20. A low-pH medium in vitro or the environment within a macrophage decreases the transcriptional levels of fimA, fimZ and lrp in Salmonella enterica serovar Typhimurium

    Indian Academy of Sciences (India)

    Ke-Chuan Wang; Yuan-Hsun Hsu; Yi-Ning Huang; Ter-Hsin Chen; Jiunn-Horng Lin; Shih-Ling Hsuan; Maw-Sheng Chien; Wei-Cheng Lee; Kuang-Sheng Yeh

    2013-09-01

    Many Salmonella Typhimurium isolates produce type 1 fimbriae and exhibit fimbrial phase variation in vitro. Static broth culture favours the production of fimbriae, while solid agar medium inhibits the generation of these appendages. Little information is available regarding whether . Typhimurium continues to produce type 1 fimbriae during in vivo growth. We used a type 1 fimbrial phase-variable strain . Typhimurium LB5010 and its derivatives to infect RAW 264.7 macrophages. Following entry into macrophages, . Typhimurium LB5010 gradually decreased the transcript levels of fimbrial subunit gene fimA, positive regulatory gene fimZ, and global regulatory gene lrp. A similar decrease in transcript levels was detected by RT-PCRwhen the pH of static brothmediumwas shifted frompH 7 to amore acidic pH 4. A fimA-deleted strain continued to multiply within macrophages as did the parental strain. An lrp deletion strain was unimpaired for in vitro growth at pH 7 or pH 4, while a strain harboring an lrp-containing plasmid exhibited impaired in vitro growth at pH 4. We propose that acidic medium, which resembles one aspect of the intracellular environment in a macrophage, inhibits type 1 fimbrial production by down-regulation of the expression of lrp, fimZ and fimA.

  1. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

    Directory of Open Access Journals (Sweden)

    Danbo Yang

    2010-12-01

    Full Text Available The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(L-g-glutamylglutamine-paclitaxel nano-conjugate (PGG-PTX. PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic.

  2. ATP-triggered anticancer drug delivery

    Science.gov (United States)

    Mo, Ran; Jiang, Tianyue; Disanto, Rocco; Tai, Wanyi; Gu, Zhen

    2014-03-01

    Stimuli-triggered drug delivery systems have been increasingly used to promote physiological specificity and on-demand therapeutic efficacy of anticancer drugs. Here we utilize adenosine-5'-triphosphate (ATP) as a trigger for the controlled release of anticancer drugs. We demonstrate that polymeric nanocarriers functionalized with an ATP-binding aptamer-incorporated DNA motif can selectively release the intercalating doxorubicin via a conformational switch when in an ATP-rich environment. The half-maximal inhibitory concentration of ATP-responsive nanovehicles is 0.24 μM in MDA-MB-231 cells, a 3.6-fold increase in the cytotoxicity compared with that of non-ATP-responsive nanovehicles. Equipped with an outer shell crosslinked by hyaluronic acid, a specific tumour-targeting ligand, the ATP-responsive nanocarriers present an improvement in the chemotherapeutic inhibition of tumour growth using xenograft MDA-MB-231 tumour-bearing mice. This ATP-triggered drug release system provides a more sophisticated drug delivery system, which can differentiate ATP levels to facilitate the selective release of drugs.

  3. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

    International Nuclear Information System (INIS)

    The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(l-γ-glutamylglutamine)-paclitaxel nano-conjugate (PGG-PTX). PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic

  4. Gamma irradiation reduces the immunological toxicity of doxorubicin, anticancer drug

    Science.gov (United States)

    Kim, Jae-Hun; Sung, Nak-Yun; Raghavendran, H. Balaji; Yoon, Yohan; Song, Beom-Seok; Choi, Jong-il; Yoo, Young-Choon; Byun, Myung-Woo; Hwang, Young-Jeong; Lee, Ju-Woon

    2009-07-01

    Doxorubicin (DOX) is a widely used anticancer agent, but exhibits some immunological toxicity to patients during chemotherapy. The present study was conducted to evaluate the effect of gamma irradiation on the immunological response and the inhibition activity on in vivo tumor mass of DOX. The results showed that DOX irradiated at 10 and 20 kGy reduce the inhibition of mouse peritoneal macrophage proliferation and induce the release of cytokines (TNF-α and IL-6) when compared with non-irradiated DOX. The cytotoxicity against human breast (MCF-7), murine colon adenocarcinoma (Colon 26) and human monocytic (THP-1) tumor cell were not significantly different between non-irradiated and irradiated DOX ( Pstatistically non-significant as compared with non-irradiated DOX. In conclusion, gamma irradiation could be regarded as a potential method for reducing the immunological toxicity of DOX. Further researches is needed to reveal the formation and activity of radiolysis products by gamma irradiation.

  5. Structural analogues of diosgenyl saponins: synthesis and anticancer activity.

    Science.gov (United States)

    Kaskiw, Matthew J; Tassotto, Mary Lynn; Mok, Mac; Tokar, Stacey L; Pycko, Roxanne; Th'ng, John; Jiang, Zi-Hua

    2009-11-15

    Saponins display various biological activities including anti-tumor activity. Recently intensive research has been focused on developing saponins for tumor therapies. The diosgenyl saponin dioscin is one of the most common steroidal saponins and exhibits potent anticancer activity in several human cancer cells through apoptosis-inducing pathways. In this paper, we describe the synthesis of several diosgenyl saponin analogues containing either a 2-amino-2-deoxy-beta-d-glucopyranosyl residue or an alpha-l-rhamnopyranosyl-(1-->4)-2-amino-2-deoxy-beta-d-glucopyranosyl residue with different acyl substituents on the amino group. The cytotoxic activity of these compounds was evaluated in MCF-7 breast cancer cells and HeLa cervical cancer cells. Structure-activity relationship studies show that the disaccharide saponin analogues are in general less active than their corresponding monosaccharide analogues. The incorporation of an aromatic nitro functionality into these saponin analogues does not exhibit significant effect on their cytotoxic activity. PMID:19819703

  6. Phytochemicals and Biogenic Metallic Nanoparticles as Anticancer Agents.

    Science.gov (United States)

    Rao, Pasupuleti Visweswara; Nallappan, Devi; Madhavi, Kondeti; Rahman, Shafiqur; Jun Wei, Lim; Gan, Siew Hua

    2016-01-01

    Cancer is a leading cause of death worldwide. Several classes of drugs are available to treat different types of cancer. Currently, researchers are paying significant attention to the development of drugs at the nanoscale level to increase their target specificity and to reduce their concentrations. Nanotechnology is a promising and growing field with multiple subdisciplines, such as nanostructures, nanomaterials, and nanoparticles. These materials have gained prominence in science due to their size, shape, and potential efficacy. Nanomedicine is an important field involving the use of various types of nanoparticles to treat cancer and cancerous cells. Synthesis of nanoparticles targeting biological pathways has become tremendously prominent due to the higher efficacy and fewer side effects of nanodrugs compared to other commercial cancer drugs. In this review, different medicinal plants and their active compounds, as well as green-synthesized metallic nanoparticles from medicinal plants, are discussed in relation to their anticancer activities. PMID:27057273

  7. Phytochemicals and Biogenic Metallic Nanoparticles as Anticancer Agents

    Directory of Open Access Journals (Sweden)

    Pasupuleti Visweswara Rao

    2016-01-01

    Full Text Available Cancer is a leading cause of death worldwide. Several classes of drugs are available to treat different types of cancer. Currently, researchers are paying significant attention to the development of drugs at the nanoscale level to increase their target specificity and to reduce their concentrations. Nanotechnology is a promising and growing field with multiple subdisciplines, such as nanostructures, nanomaterials, and nanoparticles. These materials have gained prominence in science due to their size, shape, and potential efficacy. Nanomedicine is an important field involving the use of various types of nanoparticles to treat cancer and cancerous cells. Synthesis of nanoparticles targeting biological pathways has become tremendously prominent due to the higher efficacy and fewer side effects of nanodrugs compared to other commercial cancer drugs. In this review, different medicinal plants and their active compounds, as well as green-synthesized metallic nanoparticles from medicinal plants, are discussed in relation to their anticancer activities.

  8. Polymeric micelles in anticancer therapy : targeting, imaging and triggered release

    NARCIS (Netherlands)

    Oerlemans, Chris; Bult, Wouter; Bos, Mariska; Storm, Gert; Nijsen, J Frank W; Hennink, Wim E

    2010-01-01

    Micelles are colloidal particles with a size around 5-100 nm which are currently under investigation as carriers for hydrophobic drugs in anticancer therapy. Currently, five micellar formulations for anticancer therapy are under clinical evaluation, of which Genexol-PM has been FDA approved for use

  9. Preclinical pharmacodynamic evaluation of antibiotic nitroxoline for anticancer drug repurposing

    OpenAIRE

    Zhang, Qi; Wang, Shanshan; Yang, Dexuan; PAN, KEVIN; Li, Linna; Yuan, Shoujun

    2016-01-01

    The established urinary antibiotic nitroxoline has recently regained considerable attention, due to its potent activities in inhibiting angiogenesis, inducing apoptosis and blocking cancer cell invasion. These features make nitroxoline an excellent candidate for anticancer drug repurposing. To rapidly advance nitroxoline repurposing into clinical trials, the present study performed systemic preclinical pharmacodynamic evaluation of its anticancer activity, including a methyl thiazolyl tetrazo...

  10. Paclitaxel Through the Ages of Anticancer Therapy: Exploring Its Role in Chemoresistance and Radiation Therapy

    Directory of Open Access Journals (Sweden)

    Anna Maria Barbuti

    2015-12-01

    Full Text Available Paclitaxel (Taxol® is a member of the taxane class of anticancer drugs and one of the most common chemotherapeutic agents used against many forms of cancer. Paclitaxel is a microtubule-stabilizer that selectively arrests cells in the G2/M phase of the cell cycle, and found to induce cytotoxicity in a time and concentration-dependent manner. Paclitaxel has been embedded in novel drug formulations, including albumin and polymeric micelle nanoparticles, and applied to many anticancer treatment regimens due to its mechanism of action and radiation sensitizing effects. Though paclitaxel is a major anticancer drug which has been used for many years in clinical treatments, its therapeutic efficacy can be limited by common encumbrances faced by anticancer drugs. These encumbrances include toxicities, de novo refraction, and acquired multidrug resistance (MDR. This article will give a current and comprehensive review of paclitaxel, beginning with its unique history and pharmacology, explore its mechanisms of drug resistance and influence in combination with radiation therapy, while highlighting current treatment regimens, formulations, and new discoveries.

  11. Roles of Reactive Oxygen Species in Anticancer Therapy with Salvia miltiorrhiza Bunge

    Directory of Open Access Journals (Sweden)

    Yu-Chiang Hung

    2016-01-01

    Full Text Available Cancer is a leading cause of death worldwide. We aim to provide a systematic review about the roles of reactive oxygen species (ROS in anticancer therapy with Salvia miltiorrhiza Bunge (Danshen. Danshen, including its lipophilic and hydrophilic constituents, is potentially beneficial for treating various cancers. The mechanisms of ROS-related anticancer effects of Danshen vary depending on the specific type of cancer cells involved. Danshen may enhance TNF-α-induced apoptosis, upregulate caspase-3, caspase-8, caspase-9, endoplasmic reticulum stress, P21, P53, Bax/Bcl-2, DR5, and AMP-activated protein kinase, or activate the p38/JNK, mitogen-activated protein kinase, and FasL signaling pathways. Conversely, Danshen may downregulate human telomerase reverse transcriptase mRNA, telomerase, survivin, vascular endothelial growth factor/vascular endothelial growth factor receptor 2, CD31, NF-κB, Erk1/2, matrix metalloproteinases, microtubule assembly, and receptor tyrosine kinases including epidermal growth factor receptors, HER2, and P-glycoprotein and inhibit the PI3K/Akt/mTOR or estrogen receptor signaling pathways. Therefore, Danshen may inhibit cancer cells proliferation through antioxidation on tumor initiation and induce apoptosis or autophagy through ROS generation on tumor progression, tumor promotion, and tumor metastasis. Based on the available evidence regarding its anticancer properties, this review provides new insights for further anticancer research or clinical trials with Danshen.

  12. Identification and characterization of a potent anticancer fraction from the leaf extracts of Moringa oleifera L.

    Science.gov (United States)

    Krishnamurthy, Praveen T; Vardarajalu, Ambalika; Wadhwani, Ashish; Patel, Viral

    2015-02-01

    Anticancer potential of Moringa oleifera L. extracts have been well established. However, there are no reports on the isolated molecules/fractions from these extracts which are responsible for the anticancer/cytotoxic activity. Thus, in the present study, we explored the same. The n-hexane, chloroform, ethyl acetate, methanol extracts of the M. oleifera leaves and 15 fractions (F1 to F15) of ethyl acetate extract were evaluated for their in vitro and in vivo anticancer activity using Hep-2 cell lines and Dalton's lymphoma ascites model in mice, respectively. Among the tested samples, the F1 fraction showed potential cytotoxic effect in Hep-2 cell lines with a CTC50 value of 12.5 ± 0.5 μg/ml. In vivo studies with the doses 5 and 10 mg/kg, p.o. demonstrated significant reduction in body weight and increased the mean survival time compared to the control group. These results were also comparable to the standard, 5-Fluorouracil, treated animals. We have also successfully isolated and characterized the anticancer fraction, F1 from the leaves of M. oleifera L. PMID:25757240

  13. Nanoformulation improves activity of the (pre)clinical anticancer ruthenium complex KP1019.

    Science.gov (United States)

    Heffeter, P; Riabtseva, A; Senkiv, Y; Kowol, C R; Körner, W; Jungwith, U; Mitina, N; Keppler, B K; Konstantinova, T; Yanchuk, I; Stoika, R; Zaichenko, A; Berger, W

    2014-05-01

    Ruthenium anticancer drugs belong to the most promising non-platinum anticancer metal compounds in clinical evaluation. However, although the clinical results are promising regarding both activity and very low adverse effects, the clinical application is currently hampered by the limited solubility and stability of the drug in aqueous solution. Here, we present a new nanoparticle formulation based on polymer-based micelles loaded with the anticancer lead ruthenium compound KP1019. Nanoprepared KP1019 was characterised by enhanced stability in aqueous solutions. Moreover, the nanoparticle formulation facilitated cellular accumulation of KP1019 (determined by ICP-MS measurements) resulting in significantly lowered IC50 values. With regard to the mode of action, increased cell cycle arrest in G2/M phase (PI-staining), DNA damage (Comet assay) as well as enhanced levels of apoptotic cell death (caspase 7 and PARP cleavage) were found in HCT116 cells treated with the new nanoformulation of KP1019. Summarizing, we present for the first time evidence that nanoformulation is a feasible strategy for improving the stability as well as activity of experimental anticancer ruthenium compounds. PMID:24734541

  14. Anti-cancer activity of bromelain nanoparticles by oral administration.

    Science.gov (United States)

    Bhatnagar, Priyanka; Patnaik, Soma; Srivastava, Amit K; Mudiam, Mohan K R; Shukla, Yogeshwer; Panda, Amulya K; Pant, Aditya B; Kumar, Pradeep; Gupta, Kailash C

    2014-12-01

    Oral administration of anti-cancer drugs is an effective alternative to improve their efficacy and reduce undesired toxicity. Bromelain (BL) is known as an effective anti-cancer phyto-therapeutic agent, however, its activity is reduced upon oral administration. In addressing the issue, BL was encapsulated in Poly(lactic-co-glycolic acid) (PLGA) to formulate nanoparticles (NPs). Further, the NPs were coated with Eudragit L30D polymer to introduce stability against the gastric acidic conditions. The resultant coated NPs were characterized for BL entrapment, proteolytic activity and mean particle size. The stability and release pattern of NPs were evaluated under simulated gastrointestinal tract (GIT) pH conditions. Cytotoxicity studies carried out in human cell lines of diverse origin have shown significant dose advantage (-7-10 folds) with NPs in reducing the IC50 values compared with free BL. The cellular uptake of NPs in MCF-7, HeLa and Caco-2 cells monolayer was significantly enhanced several folds as compared to free BL. Altered expression of marker proteins associated with apoptosis and cell death (P53, P21, Bcl2, Bax) also confirmed the enhanced anti-carcinogenic potential of formulated NPs. Oral administration of NPs reduced the tumor burden of Ehrlich ascites carcinoma (EAC) in Swiss albino mice and also increased their life-span (160.0 ± 5.8%) when compared with free BL (24 ± 3.2%). The generation of reactive oxygen species, induction of apoptosis and impaired mitochondrial membrane potential in EAC cells treated with NPs confirmed the suitability of Eudragit coated BL-NPs as a promising candidate for oral chemotherapy. PMID:26000370

  15. Anti-cancer efficacy of silybin derivatives -- a structure-activity relationship.

    Directory of Open Access Journals (Sweden)

    Chapla Agarwal

    Full Text Available Silybin or silibinin, a flavonolignan isolated from Milk thistle seeds, is one of the popular dietary supplements and has been extensively studied for its antioxidant, hepatoprotective and anti-cancer properties. We have envisioned that potency of silybin could be further enhanced through suitable modification/s in its chemical structure. Accordingly, here, we synthesized and characterized a series of silybin derivatives namely 2,3-dehydrosilybin (DHS, 7-O-methylsilybin (7OM, 7-O-galloylsilybin (7OG, 7,23-disulphatesilybin (DSS, 7-O-palmitoylsilybin (7OP, and 23-O-palmitoylsilybin (23OP; and compared their anti-cancer efficacy using human bladder cancer HTB9, colon cancer HCT116 and prostate carcinoma PC3 cells. In all the 3 cell lines, DHS, 7OM and 7OG demonstrated better growth inhibitory effects and compared to silybin, while other silybin derivatives showed lesser or no efficacy. Next, we prepared the optical isomers (A and B of silybin, DHS, 7OM and 7OG, and compared their anti-cancer efficacy. Isomers of these three silybin derivatives also showed better efficacy compared with respective silybin isomers, but in each, there was no clear cut silybin A versus B isomer activity preference. Further studies in HTB cells found that DHS, 7OM and 7OG exert better apoptotic activity than silibinin. Clonogenic assays in HTB9 cells further confirmed that both the racemic mixtures as well as pure optical isomers of DHS, 7OM and 7OG were more effective than silybin. Overall, these results clearly suggest that the anti-cancer efficacy of silybin could be significantly enhanced through structural modifications, and identify strong anti-cancer efficacy of silybin derivatives, namely DHS, 7OM, and 7OG, signifying that their efficacy and toxicity should be evaluated in relevant pre-clinical cancer models in rodents.

  16. Combined bacterial and viral treatment: a novel anticancer strategy.

    Science.gov (United States)

    Krzykawski, Marcin P

    2015-01-01

    An idea for a new combination therapy will be described herein. It is a proposition to combine viral and bacterial anticancer therapies and make them fight cancer in concert. We analyzed biological anticancer therapies and found overlapping advantages and disadvantages which led us to the conclusion that the combination therapy has the potential to create a new therapeutic quality. It is surprising how many weaknesses of viral anticancer therapy are the strengths of bacterial anticancer therapies and the other way round. We review the facts behind this concept and try to assess its value. We propose a few strategies how to combine these two therapies but as far as the review can go, final answers will have to come from the experiments. This review is the first attempt to describe a new strategy and understand the means for this idea but also to raise new questions and discuss new ways to look at anti-cancer treatment. PMID:26648783

  17. Breaking through the central tolerance ceiling to unleash anticancer immune responses

    OpenAIRE

    Su, Maureen A.; Anderson, Mark S.

    2014-01-01

    Central thymic tolerance mechanisms create a formidable barrier against the generation of self-reactive T cells. While preventing autoimmunity, this barrier also limits an effective antitumor immunological response. We recently reported that anti-RANKL blocking antibody breaches this central tolerance barrier, thus increasing the repertoire of melanoma reactive T cells. Thus, central tolerance blockade may be an effective therapeutic strategy to enhance anticancer immunity.

  18. Screening of anticancer activity from agarwood essential oil

    Directory of Open Access Journals (Sweden)

    Yumi Zuhanis Has-Yun Hashim

    2014-01-01

    Full Text Available Background: Agarwood is a priceless non-timber forest product from Aquilaria species belonging to the Thymelaeaceae family. As a result of a defence mechanism to fend off pathogens, Aquilaria species develop agarwood or resin which can be used for incense, perfumery, and traditional medicines. Evidences from ethnopharmacological practices showed that Aquilaria spp. have been traditionally used in the Ayurvedic practice and Chinese medicine to treat various diseases particularly the inflammatory-associated diseases. There have been no reports on traditional use of agarwood towards cancer treatment. However, this is most probably due to the fact that cancer nomenclature is used in modern medicine to describe the diseases associated with unregulated cell growth in which inflammation and body pain are involved. Objective: The aim of this current study was therefore to investigate the potential anticancer properties of agarwood essential oil obtained from distillation of agarwood (resin towards MCF-7 breast cancer cells. Materials and Methods: The essential oil was subjected to screening assays namely cell viability, cell attachment and sulforhodamine B (SRB-based cytotoxicity assay to determine the IC 50 value. Results: The agarwood essential oil caused reduction of the cell number in both the cell viability and attachment assay suggesting a cumulative effect of the cell killing, inhibition of the cell attachment and or causing cells to detach. The agarwood essential oil showed IC 50 value of 900 μg/ml towards the cancer cells. Conclusion: The agarwood essential oil exhibited anticancer activity which supports the traditional use against the inflammatory-associated diseases. This warrants further investigation towards the development of alternative remedy towards cancer.

  19. Spermine oxidase (SMO) activity in breast tumor tissues and biochemical analysis of the anticancer spermine analogues BENSpm and CPENSpm

    International Nuclear Information System (INIS)

    Polyamine metabolism has a critical role in cell death and proliferation representing a potential target for intervention in breast cancer (BC). This study investigates the expression of spermine oxidase (SMO) and its prognostic significance in BC. Biochemical analysis of Spm analogues BENSpm and CPENSpm, utilized in anticancer therapy, was also carried out to test their property in silico and in vitro on the recombinant SMO enzyme. BC tissue samples were analyzed for SMO transcript level and SMO activity. Student's t test was applied to evaluate the significance of the differences in value observed in T and NT samples. The structure modeling analysis of BENSpm and CPENSpm complexes formed with the SMO enzyme and their inhibitory activity, assayed by in vitro experiments, were examined. Both the expression level of SMO mRNA and SMO enzyme activity were significantly lower in BC samples compared to NT samples. The modeling of BENSpm and CPENSpm complexes formed with SMO and their inhibition properties showed that both were good inhibitors. This study shows that underexpression of SMO is a negative marker in BC. The SMO induction is a remarkable chemotherapeutical target. The BENSpm and CPENSpm are efficient SMO inhibitors. The inhibition properties shown by these analogues could explain their poor positive outcomes in Phases I and II of clinical trials

  20. System engineering approach to planning anticancer therapies

    CERN Document Server

    Świerniak, Andrzej; Smieja, Jaroslaw; Puszynski, Krzysztof; Psiuk-Maksymowicz, Krzysztof

    2016-01-01

    This book focuses on the analysis of cancer dynamics and the mathematically based synthesis of anticancer therapy. It summarizes the current state-of-the-art in this field and clarifies common misconceptions about mathematical modeling in cancer. Additionally, it encourages closer cooperation between engineers, physicians and mathematicians by showing the clear benefits of this without stating unrealistic goals. Development of therapy protocols is realized from an engineering point of view, such as the search for a solution to a specific control-optimization problem. Since in the case of cancer patients, consecutive measurements providing information about the current state of the disease are not available, the control laws are derived for an open loop structure. Different forms of therapy are incorporated into the models, from chemotherapy and antiangiogenic therapy to immunotherapy and gene therapy, but the class of models introduced is broad enough to incorporate other forms of therapy as well. The book be...

  1. Synthesis and anticancer evaluation of spermatinamine analogues

    KAUST Repository

    Moosa, Basem A.

    2016-02-04

    Spermatinamine was isolated from an Australian marine sponge, Pseudoceratina sp. as an inhibitor of isoprenylcystiene carboxyl methyltransferase (Icmt), an attractive and novel anticancer target. Herein, we report the synthesis of spermatinamine analogues and their cytotoxic evaluation against three human cancer cell lines i.e. cervix adenocarcinoma (HeLa), breast adenocarcinoma (MCF-7), and prostate carcinoma (DU145). Analogues 12, 14 and 15 were found to be the most potent against one or more cell lines with the IC50 values in the range of 5 - 10 μM. The obtained results suggested that longer polyamine linker along with aromatic oxime substitution provided the most potent analogue compounds against cancer cell lines.

  2. Melatonin Counteracts at a Transcriptional Level the Inflammatory and Apoptotic Response Secondary to Ischemic Brain Injury Induced by Middle Cerebral Artery Blockade in Aging Rats

    OpenAIRE

    Paredes, Sergio D.; Rancan, Lisa; Kireev, Roman; González, Alberto; Louzao, Pedro; González, Pablo; Rodríguez-Bobada, Cruz; García, Cruz; Vara, Elena; Tresguerres, Jesús A.F.

    2015-01-01

    Abstract Aging increases oxidative stress and inflammation. Melatonin counteracts inflammation and apoptosis. This study investigated the possible protective effect of melatonin on the inflammatory and apoptotic response secondary to ischemia induced by blockade of the right middle cerebral artery (MCA) in aging male Wistar rats. Animals were subjected to MCA obstruction. After 24 h or 7 days of procedure, 14-month-old nontreated and treated rats with a daily dose of 10 mg/kg melatonin were s...

  3. In Vitro and Ex Vivo Evaluations of Lipid Anti-Cancer Nanoformulations: Insights and Assessment of Bioavailability Enhancement.

    Science.gov (United States)

    Jain, Ankitkumar S; Dhawan, Vivek V; Sarmento, Bruno; Nagarsenker, Mangal S

    2016-06-01

    Lipid-based nanoformulations have been extensively investigated for improving oral efficacy of plethora of drugs. Chemotherapeutic agents remain a preferred option for effective management of cancer; however, most chemotherapeutic agents suffer from limitation of poor oral bioavailability that is associated with their physicochemical properties. Drug delivery via lipid-based nanosystems possesses strong rational and potential for improving oral bioavailability of such anti-cancer molecules through various mechanisms, viz. improving their gut solubilisation owing to micellization, improving mucosal permeation, improving lymphatic uptake, inhibiting intestinal metabolism and/or inhibiting P-glycoprotein efflux of molecules in the gastrointestinal tract. Various in vitro characterization techniques have been reported in literature that aid in getting insights into mechanisms of lipid-based nanodevices in improving oral efficacy of anti-cancer drugs. The review focuses on different characterization techniques that can be employed for evaluation of lipid-based nanosystems and their role in effective anti-cancer drug delivery. PMID:27068527

  4. Moringa oleifera as an Anti-Cancer Agent against Breast and Colorectal Cancer Cell Lines

    Science.gov (United States)

    Al-Asmari, Abdulrahman Khazim; Albalawi, Sulaiman Mansour; Athar, Md Tanwir; Khan, Abdul Quaiyoom; Al-Shahrani, Hamoud; Islam, Mozaffarul

    2015-01-01

    In this study we investigated the anti-cancer effect of Moringa oleifera leaves, bark and seed extracts. When tested against MDA-MB-231 and HCT-8 cancer cell lines, the extracts of leaves and bark showed remarkable anti-cancer properties while surprisingly, seed extracts exhibited hardly any such properties. Cell survival was significantly low in both cells lines when treated with leaves and bark extracts. Furthermore, a striking reduction (about 70–90%) in colony formation as well as cell motility was observed upon treatment with leaves and bark. Additionally, apoptosis assay performed on these treated breast and colorectal cancer lines showed a remarkable increase in the number of apoptotic cells; with a 7 fold increase in MD-MB-231 to an increase of several fold in colorectal cancer cell lines. However, no significant apoptotic cells were detected upon seeds extract treatment. Moreover, the cell cycle distribution showed a G2/M enrichment (about 2–3 fold) indicating that these extracts effectively arrest the cell progression at the G2/M phase. The GC-MS analyses of these extracts revealed numerous known anti-cancer compounds, namely eugenol, isopropyl isothiocynate, D-allose, and hexadeconoic acid ethyl ester, all of which possess long chain hydrocarbons, sugar moiety and an aromatic ring. This suggests that the anti-cancer properties of Moringa oleifera could be attributed to the bioactive compounds present in the extracts from this plant. This is a novel study because no report has yet been cited on the effectiveness of Moringa extracts obtained in the locally grown environment as an anti-cancer agent against breast and colorectal cancers. Our study is the first of its kind to evaluate the anti-malignant properties of Moringa not only in leaves but also in bark. These findings suggest that both the leaf and bark extracts of Moringa collected from the Saudi Arabian region possess anti-cancer activity that can be used to develop new drugs for treatment of

  5. Identification of an anticancer compound against HT-29 cells from Phellinus linteus grown on germinated brown rice

    Institute of Scientific and Technical Information of China (English)

    Tae-Il Jeon; Chang-Hwa Jung; Jeong-Yong Cho; Dong Ki Park; Jae-Hak Moon

    2013-01-01

    Objective:To isolate and identify the anticancer compound against proliferation of human colon cancer cells from ethyl acetate (EtOAc) extract of Phellinus linteus grown on germinated brown rice (PB). Methods: EtOAc extract of PB was partitioned with n-hexane, EtOAc, and water-saturated n-butanol. Anticancer compound of n-hexane layer was isolated and identified by HPLC and NMR, respectively. Cytotoxicity against HT-29 cells was tested by SRB assay. Results: The n-hexane layer obtained after solvent fractionation of PB EtOAc extracts showed a potent anticancer activity against the HT-29 cell line. Atractylenolide I, a eudesmane-type sesquiterpene lactone, a major anticancer substance of PB, was isolated from the n-hexane layer by silica gel column chromatography and preparative-HPLC. This structure was elucidated by one-and two-dimensional NMR spectroscopic data. Atractylenolide I has not been reported in mushrooms or rice as of yet. The isolated compound dose-dependently inhibited the growth of HT-29 human colon cancer cells. Conclusions:Atractylenolide I might contribute to the anticancer effect of PB.

  6. Nizwaside: a new anticancer pregnane glycoside from the sap of Desmidorchis flava.

    Science.gov (United States)

    Hussain, Hidayat; Raees, Muhammad Adil; Rehman, Najeeb Ur; Al-Rawahi, Ahmed; Csuk, René; Khan, Husain Yar; Abbas, Ghulam; Al-Broumi, Mohammed Abdullah; Green, Ivan R; Elyassi, Ali; Mahmood, Talat; Al-Harrasi, Ahmed

    2015-12-01

    The sap from the succulent Desmidorchis flava (N.E.Br) Meve and Liede yielded a new pregnane glycoside, named nizwaside whose structure was established using 1D and 2D NMR techniques as well as mass spectrometry (ESIMS). Nizwaside was tested for anticancer, DPPH antioxidant, urease enzyme inhibition, α-glucosidase enzyme inhibition and acetylcholinesterase inhibition activities. Interestingly, nizwaside showed significant anti-proliferative effects on MDA MB231 breast cancer cells with an IC(50) of 23.5 µg/ml. Moreover, nizwaside was more effective than Doxorubicin, a well-known clinical anticancer drug, in suppressing MDA MB231 cell proliferation even at concentrations lower than that of Doxorubicin (75 µg/ml nizwaside vs. 100 µg/ml Doxorubicin). On the other hand, nizwaside showed relatively weak antioxidant activity with 15 % inhibition. PMID:26335549

  7. In vivo nanotoxicology of hybrid systems based on copolymer/silica/anticancer drug

    Science.gov (United States)

    Silveira, C. P.; Paula, A. J.; Apolinário, L. M.; Fávaro, W. J.; Durán, N.

    2015-05-01

    One of the major problems in cancer therapies is the high occurrence of side effects intrinsic of anticancer drugs. Doxorrubicin is a conventional anticancer molecule used to treat a wide range of cancer, such as breast, ovarian and prostate. However, its use is associated with a number of side effects like multidrug resistance and cardiotoxicity. The association with nanomaterials has been considered in the past decade to overcome the high toxicity of these drugs. In this context, mesoporous silica nanoparticles are great candidates to be used as carriers once they are very biocompatible. Taking into account the combination of nanoparticles and doxorrubicin, we treated rats with chemically induced prostate cancer with systems based on mesoporous silica nanoparticles and a thermoreversible block copolymer (Pluronic F-127) containing doxorrubicin. Preliminary results show a possible improvement in tumor conditions proportional to the concentration of the nanoparticles, opening a perspective to use mesoporous silica nanoparticles as carrier for doxorrubicin in prostate cancer treatment.

  8. Dietary Oil Source and Selenium Supplementation Modulate Fads2 and Elovl5 Transcriptional Levels in Liver and Brain of Meagre (Argyrosomus regius).

    Science.gov (United States)

    Silva-Brito, Francisca; Magnoni, Leonardo J; Fonseca, Sthelio Braga; Peixoto, Maria João; Castro, L Filipe C; Cunha, Isabel; de Almeida Ozório, Rodrigo Otávio; Magalhães, Fernando Antunes; Gonçalves, José Fernando Magalhães

    2016-06-01

    The meagre (Argyrosomus regius) is taking on increasing importance in the aquaculture industry. In view of the limited supply of fish oil (FO) as a feed ingredient, the study of the capacity to biosynthesize long-chain polyunsaturated fatty acids (LC-PUFA) from alternative dietary oil sources is important. We analyzed changes in fatty acid (FA) desaturase 2 (fads2) and FA elongase 5 (elovl5) mRNA levels in livers and brains in response to FO replacement with a blend of vegetable oils (VO) and selenium (Se) supplementation. Fish were fed for 60 days with either a diet containing FO or a diet including VO, each supplemented or not with organic Se. Results showed that fads2 and elovl5 transcription was higher in liver when fish were fed VO diets. The brain mRNA levels of both genes were not affected by the dietary replacement of FO by VO. FA composition in the liver and skeletal muscle was altered by FO replacement, particularly by decreasing eicosapentaenoic acid and docosahexaenoic acid contents. The α-linolenic, linoleic, and arachidonic acid contents increased in both liver and brain of fish fed VO diets. The effect of Se supplementation on lipid metabolism was evident only in fish fed FO, showing a decrease in the transcription of hepatic fads2. Results indicate that the total replacement of FO by VO in diets modulates the expression of genes involved in LC-PUFA biosynthesis in meagre, affecting the FA profile of the fish flesh. PMID:27169705

  9. Anticancer Activities of Trichostatin A on Maligant Lymphoid Cells

    Institute of Scientific and Technical Information of China (English)

    SUN Chunyan; LIU Xinyue; CHEN Yan; LIU Fang

    2006-01-01

    The anticancer activity of trichostain A (TSA) on human B cell non-Hodgkin's lymphoma and its mechanism were explored. The