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Sample records for anticancer transcript-level effects

  1. Effect of nitrate on activities and transcript levels of nitrate reductase and glutamine synthetase in rice

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    CAO Yun; FAN Xiao-Rong; SUN Shu-Bin; XU Guo-Hua; HU Jiang; SHEN Qi-Rong

    2008-01-01

    Real-time polymerase chain reaction analysis was used to compare the effect of NO-3 on the activities of nitrate reductase (NR) and glutamine synthetase (GS),and the transcript levels of two NR genes,OsNia1 and OsNia2,two cytceolic GS1 genes,OsGln1;1 and OsGln1;2,and one plastid GS2 gene OsGln2,in two rice (Oryza sativa L.) cultivars Nanguang (NG) and Yunjing (YJ).Both cultivars achieved greater biomass and higher total N concentration when grown in a mixed N supply than in sole NH+ nutrition.Supply of NO-3 increased NR activity in both leaves and roots.Expression of both NR genes was also substantially enhanced and transcript levels of OsNia2 were significantly higher than those of OsNia1.NO-3 also caused an increase in GS activity,but had a complex effect on the expression of the three GS genes.In roots,the OsGln1;1 transcript increased,but OsGln1;2 decreased.In leaves,NO-3 had no effect on the GS1 expression,but the transcript for OsGln2 increased both in the leaves and roots of rice with a mixed supply of N.These results suggested that the increase in GS activity might be a result of the complicated regulation of the various GS genes.In addition,the NO-3 induced increase of biomass,NR activity,GS activity,and the transcript levels of NR and GS genes were proportionally higher in NG than in YJ,indicating a stronger response of NG to NO-3 nutrition than YJ.

  2. 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.

  3. Genetic effects of an air discharge plasma on Staphylococcus aureus at the gene transcription level

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    Xu, Zimu; Wei, Jun; Shen, Jie; Liu, Yuan; Ma, Ronghua; Zhang, Zelong; Qian, Shulou; Ma, Jie; Lan, Yan; Zhang, Hao; Zhao, Ying; Xia, Weidong; Sun, Qiang; Cheng, Cheng; Chu, Paul K.

    2015-05-01

    The dynamics of gene expression regulation (at transcription level) in Staphylococcus aureus after different doses of atmospheric-pressure room-temperature air plasma treatments are investigated by monitoring the quantitative real-time polymerase chain reaction. The plasma treatment influences the transcription of genes which are associated with several important bio-molecular processes related to the environmental stress resistance of the bacteria, including oxidative stress response, biofilm formation, antibiotics resistance, and DNA damage protection/repair. The reactive species generated by the plasma discharge in the gas phase and/or induced in the liquid phase may account for these gene expression changes.

  4. 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.

  5. Effect of biotin on transcription levels of key enzymes and glutamate efflux in glutamate fermentation by Corynebacterium glutamicum.

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    Cao, Yan; Duan, Zuoying; Shi, Zhongping

    2014-02-01

    Biotin is an important factor affecting the performance of glutamate fermentation by biotin auxotrophic Corynebacterium glutamicum and glutamate is over-produced only when initial biotin content is controlled at suitable levels or initial biotin is excessive but with Tween 40 addition during fermentation. The transcription levels of key enzymes at pyruvate, isocitrate and α-ketoglutarate metabolic nodes, as well as transport protein (TP) of glutamate were investigated under the conditions of varied biotin contents and Tween 40 supplementation. When biotin was insufficient, the genes encoding key enzymes and TP were down-regulated in the early production phase, in particular, the transcription level of isocitrate dehydrogenase (ICDH) which was only 2% of that of control. Although the cells' morphology transformation and TP level were not affected, low transcription level of ICDH led to lower final glutamate concentration (64 g/L). When biotin was excessive, the transcription levels of key enzymes were at comparable levels as those of control with ICDH as an exception, which was only 3-22% of control level throughout production phase. In this case, little intracellular glutamate accumulation (1.5 mg/g DCW) and impermeable membrane resulted in non glutamate secretion into broth, even though the quantity of TP was more than 10-folds of control level. Addition of Tween 40 when biotin was excessive stimulated the expression of all key enzymes and TP, intracellular glutamate content was much higher (10-12 mg/g DCW), and final glutamate concentration reached control level (75-80 g/L). Hence, the membrane alteration and TP were indispensable in glutamate secretion. Biotin and Tween 40 influenced the expression level of ICDH and glutamate efflux, thereby influencing glutamate production.

  6. Effect of DNA methylation profile on OATP3A1 and OATP4A1 transcript levels in colorectal cancer.

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    Rawłuszko-Wieczorek, Agnieszka Anna; Horst, Nikodem; Horbacka, Karolina; Bandura, Artur Szymon; Świderska, Monika; Krokowicz, Piotr; Jagodziński, Paweł Piotr

    2015-08-01

    Epidemiological studies indicate that 17β-estradiol (E2) prevents colorectal cancer (CRC). Organic anion transporting polypeptides (OATPs) are involved in the cellular uptake of various endogenous and exogenous substrates, including hormone conjugates. Because transfer of estrone sulfate (E1-S) can contribute to intra-tissue conversion of estrone to the biologically active form -E2, it is evident that the expression patterns of OATPs may be relevant to the analysis of CRC incidence and therapy. We therefore evaluated DNA methylation and transcript levels of two members of the OATP family, OATP3A1 and OATP4A1, that may be involved in E1-S transport in colorectal cancer patients. We detected a significant reduction in OATP3A1 and a significant increase in OATP4A1 mRNA levels in cancerous tissue, compared with histopathologically unchanged tissue (n=103). Moreover, we observed DNA hypermethylation in the OATP3A1 promoter region in a small subset of CRC patients and in HCT116 and Caco-2 colorectal cancer cell lines. We also observed increased OATP3A1 transcript following treatment with 5-aza-2-deoxycytidine and sodium butyrate. The OATP4A1 promoter region was hypomethylated in analyzed tissues and CRC cell lines and was not affected by these treatments. Our results suggest a potential mechanism for OATP3A1 downregulation that involves DNA methylation during colorectal carcinogenesis.

  7. 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.

  8. The effect of aluminium-stress and exogenous spermidine on chlorophyll degradation, glutathione reductase activity and the photosystem II D1 protein gene (psbA) transcript level in lichen Xanthoria parietina.

    Science.gov (United States)

    Sen, Gulseren; Eryilmaz, Isil Ezgi; Ozakca, Dilek

    2014-02-01

    In this study, the effects of short-term aluminium toxicity and the application of spermidine on the lichen Xanthoria parietina were investigated at the physiological and transcriptional levels. Our results suggest that aluminium stress leads to physiological processes in a dose-dependent manner through differences in lipid peroxidation rate, chlorophyll content and glutathione reductase (EC 1.6.4.2) activity in aluminium and spermidine treated samples. The expression of the photosystem II D1 protein (psbA) gene was quantified using semi-quantitative RT-PCR. Increased glutathione reductase activity and psbA mRNA transcript levels were observed in the X. parietina thalli that were treated with spermidine before aluminium-stress. The results showed that the application of spermidine could mitigate aluminium-induced lipid peroxidation and chlorophyll degradation on lichen X. parietina thalli through an increase in psbA transcript levels and activity of glutathione reductase (GR) enzymes.

  9. Effects of salinity and prolactin on gene transcript levels of ion transporters, ion pumps and prolactin receptors in Mozambique tilapia intestine.

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    Seale, Andre P; Stagg, Jacob J; Yamaguchi, Yoko; Breves, Jason P; Soma, Satoshi; Watanabe, Soichi; Kaneko, Toyoji; Cnaani, Avner; Harpaz, Sheenan; Lerner, Darren T; Grau, E Gordon

    2014-09-15

    Euryhaline teleosts are faced with significant challenges during changes in salinity. Osmoregulatory responses to salinity changes are mediated through the neuroendocrine system which directs osmoregulatory tissues to modulate ion transport. Prolactin (PRL) plays a major role in freshwater (FW) osmoregulation by promoting ion uptake in osmoregulatory tissues, including intestine. We measured mRNA expression of ion pumps, Na(+)/K(+)-ATPase α3-subunit (NKAα3) and vacuolar type H(+)-ATPase A-subunit (V-ATPase A-subunit); ion transporters/channels, Na(+)/K(+)/2Cl(-) co-transporter (NKCC2) and cystic fibrosis transmembrane conductance regulator (CFTR); and the two PRL receptors, PRLR1 and PRLR2 in eleven intestinal segments of Mozambique tilapia (Oreochromis mossambicus) acclimated to FW or seawater (SW). Gene expression levels of NKAα3, V-ATPase A-subunit, and NKCC2 were generally lower in middle segments of the intestine, whereas CFTR mRNA was most highly expressed in anterior intestine of FW-fish. In both FW- and SW-acclimated fish, PRLR1 was most highly expressed in the terminal segment of the intestine, whereas PRLR2 was generally most highly expressed in anterior intestinal segments. While NKCC2, NKAα3 and PRLR2 mRNA expression was higher in the intestinal segments of SW-acclimated fish, CFTR mRNA expression was higher in FW-fish; PRLR1 and V-ATPase A-subunit mRNA expression was similar between FW- and SW-acclimated fish. Next, we characterized the effects of hypophysectomy (Hx) and PRL replacement on the expression of intestinal transcripts. Hypophysectomy reduced both NKCC2 and CFTR expression in particular intestinal segments; however, only NKCC2 expression was restored by PRL replacement. Together, these findings describe how both acclimation salinity and PRL impact transcript levels of effectors of ion transport in tilapia intestine.

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

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    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

  11. Synergistic anti-cancer effect of phenformin and oxamate.

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    W Keith Miskimins

    Full Text Available Phenformin (phenethylbiguanide; an anti-diabetic agent plus oxamate [lactate dehydrogenase (LDH inhibitor] was tested as a potential anti-cancer therapeutic combination. In in vitro studies, phenformin was more potent than metformin, another biguanide, recently recognized to have anti-cancer effects, in promoting cancer cell death in the range of 25 times to 15 million times in various cancer cell lines. The anti-cancer effect of phenformin was related to complex I inhibition in the mitochondria and subsequent overproduction of reactive oxygen species (ROS. Addition of oxamate inhibited LDH activity and lactate production by cells, which is a major side effect of biguanides, and induced more rapid cancer cell death by decreasing ATP production and accelerating ROS production. Phenformin plus oxamate was more effective than phenformin combined with LDH knockdown. In a syngeneic mouse model, phenformin with oxamate increased tumor apoptosis, reduced tumor size and (18F-fluorodeoxyglucose (FDG uptake on positron emission tomography/computed tomography compared to control. We conclude that phenformin is more cytotoxic towards cancer cells than metformin. Furthermore, phenformin and oxamate have synergistic anti-cancer effects through simultaneous inhibition of complex I in the mitochondria and LDH in the cytosol, respectively.

  12. 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

  13. Anticancer effects of Chinese herbal medicine, science or myth?

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    RUAN Wen-jing; LAI Mao-de; ZHOU Jian-guang

    2006-01-01

    Currently there is considerable interest among oncologists to find anticancer drugs in Chinese herbal medicine (CHM).In the past, clinical data showed that some herbs possessed anticancer properties, but western scientists have doubted the scientific validity of CHM due to the lack of scientific evidence from their perspective. Recently there have been encouraging results, from a western perspective, in the cancer research field regarding the anticancer effects of CHM. Experiments showed that CHM played its anticancer role by inducing apoptosis and differentiation, enhancing the immune system, inhibiting angiogenesis, reversing multidrug resistance (MDR), etc. Clinical trials demonstrated that CHM could improve survival, increase tumor response, improve quality of life, or reduce chemotherapy toxicity, although much remained to be determined regarding the objective effects of CHM in human in the context of clinical trials. Interestingly, both laboratory experiments and clinical trials have demonstrated that when combined with chemotherapy, CHM could raise the efficacy level and lower toxic reactions. These facts raised the feasibility of the combination of herbal medicines and chemotherapy, although much remained to be investigated in this area.

  14. The anticancer and antiobesity effects of Mediterranean diet.

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    Kwan, Hiu Yee; Chao, Xiaojuan; Su, Tao; Fu, Xiuqiong; Tse, Anfernee Kai Wing; Fong, Wang Fun; Yu, Zhi-Ling

    2017-01-02

    Cancers have been the leading cause of death worldwide and the prevalence of obesity is also increasing in these few decades. Interestingly, there is a direct association between cancer and obesity. Each year, more than 90,000 cancer deaths are caused by obesity or overweight. The dietary pattern in Crete, referred as the traditional Mediterranean diet, is believed to confer Crete people the low mortality rates from cancers. Nevertheless, the antiobesity effect of the Mediterranean diet is less studied. Given the causal relationship between obesity and cancer, the antiobesity effect of traditional Mediterranean diet might contribute to its anticancer effects. In this regard, we will critically review the anticancer and antiobesity effects of this diet and its dietary factors. The possible mechanisms underlying these effects will also be discussed.

  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 and molecular mechanisms of epigallocatechin-3-gallate

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    Kyoung-jin Min

    2014-03-01

    Full Text Available Epigallocatechin-3-gallate (EGCG is a type of catechin found in green tea. EGCG exhibits a variety of activities, including anti-inflammatory, antidiabetes, antiobesity, and antitumor. In this review, we focus on the antitumor effects of EGCG. EGCG inhibits carcinogen activity, tumorigenesis, proliferation, and angiogenesis, and induces cell death. These effects are associated with modulation of reactive oxygen species (ROS production. Although EGCG has a dual function of antioxidant and pro-oxidant potential, EGCG-mediated modulation of ROS production is reported to be responsible for its anticancer effects. The EGCG-mediated inhibition of nuclear factor-κB signaling is also associated with inhibition of migration, angiogenesis, and cell viability. Activation of mitogen-activated protein kinases activity upregulates the anticancer effect of EGCG on migration, invasion, and apoptosis. In addition, EGCG could also induce epigenetic modification by inhibition of DNA methyltransferase activity and regulation of acetylation on histone, leading to an upregulation of apoptosis. Although EGCG promotes strong anticancer effects by multiple mechanisms, further studies are needed to define the use of EGCG in clinical treatment.

  17. 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).

  18. 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.

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

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    Jiang Wenqi

    2008-04-01

    Full Text Available Abstract Background 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. Methods 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. Results 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 0.05. Conclusion In our model system, 5-FU/PEG-PBLG nanoparticles

  20. Systematic analysis of transcription-level effects of neurodegenerative diseases on human brain metabolism by a newly reconstructed brain-specific metabolic network

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    Mustafa Sertbaş

    2014-01-01

    Full Text Available Network-oriented analysis is essential to identify those parts of a cell affected by a given perturbation. The effect of neurodegenerative perturbations in the form of diseases of brain metabolism was investigated by using a newly reconstructed brain-specific metabolic network. The developed stoichiometric model correctly represents healthy brain metabolism, and includes 630 metabolic reactions in and between astrocytes and neurons, which are controlled by 570 genes. The integration of transcriptome data of six neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, multiple sclerosis, schizophrenia with the model was performed to identify reporter features specific and common for these diseases, which revealed metabolites and pathways around which the most significant changes occur. The identified metabolites are potential biomarkers for the pathology of the related diseases. Our model indicated perturbations in oxidative stress, energy metabolism including TCA cycle and lipid metabolism as well as several amino acid related pathways, in agreement with the role of these pathways in the studied diseases. The computational prediction of transcription factors that commonly regulate the reporter metabolites was achieved through binding-site analysis. Literature support for the identified transcription factors such as USF1, SP1 and those from FOX families are known from the literature to have regulatory roles in the identified reporter metabolic pathways as well as in the neurodegenerative diseases. In essence, the reconstructed brain model enables the elucidation of effects of a perturbation on brain metabolism and the illumination of possible machineries in which a specific metabolite or pathway acts as a regulatory spot for cellular reorganization.

  1. Anti-Cancer Effects of Xanthones from Pericarps of Mangosteen

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    Yoshinori Nozawa

    2008-03-01

    Full Text Available Mangosteen, Garcinia mangostana Linn, is a tree found in South East Asia, and its pericarps have been used as traditional medicine. Phytochemical studies have shown that they contain a variety of secondary metabolites, such as oxygenated and prenylated xanthones. Recent studies revealed that these xanthones exhibited a variety of biological activities containing anti-inflammatory, anti-bacterial, and anti-cancer effects. We previously investigated the anti-proliferative effects of four prenylated xanthones from the pericarps; α-mangostin, β-mangostin, γ-mangostin, and methoxy-β-mangostin in various human cancer cells. These xanthones are different in the number of hydroxyl and methoxy groups. Except for methoxy-β-mangostin, the other three xanthones strongly inhibited cell growth at low concentrations from 5 to 20 μM in human colon cancer DLD-1 cells. Our recent study focused on the mechanism of α-mangostin-induced growth inhibition in DLD-1 cells. It was shown that the anti-proliferative effects of the xanthones were associated with cell-cycle arrest by affecting the expression of cyclins, cdc2, and p27; G1 arrest by α- mangostin and β-mangostin, and S arrest by γ-mangostin. α-Mangostin found to induce apoptosis through the activation of intrinsic pathway following the down-regulation of signaling cascades involving MAP kinases and the serine/threonine kinase Akt. Synergistic effects by the combined treatment of α-mangostin and anti-cancer drug 5-FU was to be noted. α-Mangostin was found to have a cancer preventive effect in rat carcinogenesis bioassay and the extract from pericarps, which contains mainly α-mangostin and γ- mangostin, exhibited an enhancement of NK cell activity in a mouse model. These findings could provide a relevant basis for the development of xanthones as an agent for cancer prevention and the combination therapy with

  2. Advancement in research of anti-cancer effects of toad venom (ChanSu) and perspectives

    Institute of Scientific and Technical Information of China (English)

    Miao Liu; Li-Xing Feng; Li-Hong Hu; Xuan Liu; De-An Guo

    2015-01-01

    Toad venom, called as ChanSu in China, is a widely used traditional Chinese medicine (TCM) whose active components are mainly bufadienolides. ChanSu could exhibit cardiotonic, anti-microbial, anti-inflammatory and, most importantly, anti-cancer effects. In the present review, reports about the in vitro, in vivo and clinical anti-cancer effects of ChanSu or its representative component, bufalin, were summarized. And, reported anti-cancer mechanisms of cardenolides, structure analogues of bufadienolides, were also introduced. Based on the results got from research of ChanSu/bufalin and the results from cardenolides, possible signal network related to the anti-cancer effects of ChanSu/bufalin was predicted. Furthermore, future potential use of ChanSu in anti-cancer therapy was discussed.

  3. In vitro evaluation of anticancer effect and neurotoxicity of Styrylpyrone derivative (SPD)

    Science.gov (United States)

    Yip, Chee-Wai; Nagaoka, Yasuo; Nor, Norefrina Shafinaz Md.; Ibrahim, Nazlina

    2016-11-01

    The increasing number of death due to cancer emphasizes the need of novel anticancer agents. Styrylpyrone derivative (SPD) was previously found to have potential anticancer action towards many types of cancer. Some of the SPD-anticancer mechanisms were elucidated as induction of cancer cell apoptosis. However, more understanding on cancer cell type specific action of SPD-anticancer effects needs to be evaluated. HCT-116 cell line, a type of human colon carcinoma, was used to study SPD-anticancer effect. It was found that SPD concentration as low as 0.25 µM was able to inhibit 80% growth of cancer cells. IC50 value of SPD for HCT-116 was found to be 0.038 µM. Neurotoxicity test, carried out to determine the adverse effect of SPD towards nerve cells, gives CC50 value as 4.88 µM, thus concluded it to be a neurotoxic compound.

  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. Molecular Targets Underlying the Anticancer Effects of Quercetin: An Update

    Directory of Open Access Journals (Sweden)

    Fazlullah Khan

    2016-08-01

    Full Text Available Quercetin, a medicinally important member of the flavonoid family, is one of the most prominent dietary antioxidants. It is present in a variety of foods—including fruits, vegetables, tea, wine, as well as other dietary supplements—and is responsible for various health benefits. Numerous pharmacological effects of quercetin include protection against diseases, such as osteoporosis, certain forms of malignant tumors, and pulmonary and cardiovascular disorders. Quercetin has the special ability of scavenging highly reactive species, such as hydrogen peroxide, superoxide anion, and hydroxyl radicals. These oxygen radicals are called reactive oxygen species, which can cause oxidative damage to cellular components, such as proteins, lipids, and deoxyribonucleic acid. Various oxygen radicals play important roles in pathophysiological and degenerative processes, such as aging. Subsequently, several studies have been performed to evaluate possible advantageous health effects of quercetin and to collect scientific evidence for these beneficial health claims. These studies also gather data in order to evaluate the exact mechanism(s of action and toxicological effects of quercetin. The purpose of this review is to present and critically analyze molecular pathways underlying the anticancer effects of quercetin. Current limitations and future directions of research on this bioactive dietary polyphenol are also critically discussed.

  6. Molecular Targets Underlying the Anticancer Effects of Quercetin: An Update

    Science.gov (United States)

    Khan, Fazlullah; Niaz, Kamal; Maqbool, Faheem; Ismail Hassan, Fatima; Abdollahi, Mohammad; Nagulapalli Venkata, Kalyan C.; Nabavi, Seyed Mohammad; Bishayee, Anupam

    2016-01-01

    Quercetin, a medicinally important member of the flavonoid family, is one of the most prominent dietary antioxidants. It is present in a variety of foods—including fruits, vegetables, tea, wine, as well as other dietary supplements—and is responsible for various health benefits. Numerous pharmacological effects of quercetin include protection against diseases, such as osteoporosis, certain forms of malignant tumors, and pulmonary and cardiovascular disorders. Quercetin has the special ability of scavenging highly reactive species, such as hydrogen peroxide, superoxide anion, and hydroxyl radicals. These oxygen radicals are called reactive oxygen species, which can cause oxidative damage to cellular components, such as proteins, lipids, and deoxyribonucleic acid. Various oxygen radicals play important roles in pathophysiological and degenerative processes, such as aging. Subsequently, several studies have been performed to evaluate possible advantageous health effects of quercetin and to collect scientific evidence for these beneficial health claims. These studies also gather data in order to evaluate the exact mechanism(s) of action and toxicological effects of quercetin. The purpose of this review is to present and critically analyze molecular pathways underlying the anticancer effects of quercetin. Current limitations and future directions of research on this bioactive dietary polyphenol are also critically discussed. PMID:27589790

  7. Molecular Targets Underlying the Anticancer Effects of Quercetin: An Update.

    Science.gov (United States)

    Khan, Fazlullah; Niaz, Kamal; Maqbool, Faheem; Ismail Hassan, Fatima; Abdollahi, Mohammad; Nagulapalli Venkata, Kalyan C; Nabavi, Seyed Mohammad; Bishayee, Anupam

    2016-08-29

    Quercetin, a medicinally important member of the flavonoid family, is one of the most prominent dietary antioxidants. It is present in a variety of foods-including fruits, vegetables, tea, wine, as well as other dietary supplements-and is responsible for various health benefits. Numerous pharmacological effects of quercetin include protection against diseases, such as osteoporosis, certain forms of malignant tumors, and pulmonary and cardiovascular disorders. Quercetin has the special ability of scavenging highly reactive species, such as hydrogen peroxide, superoxide anion, and hydroxyl radicals. These oxygen radicals are called reactive oxygen species, which can cause oxidative damage to cellular components, such as proteins, lipids, and deoxyribonucleic acid. Various oxygen radicals play important roles in pathophysiological and degenerative processes, such as aging. Subsequently, several studies have been performed to evaluate possible advantageous health effects of quercetin and to collect scientific evidence for these beneficial health claims. These studies also gather data in order to evaluate the exact mechanism(s) of action and toxicological effects of quercetin. The purpose of this review is to present and critically analyze molecular pathways underlying the anticancer effects of quercetin. Current limitations and future directions of research on this bioactive dietary polyphenol are also critically discussed.

  8. The Extraction, Anticancer Effect, Bioavailability, and Nanotechnology of Baicalin

    Science.gov (United States)

    Moore, Ondrea A.; Gao, Ying; Chen, Allen Y.; Brittain, Ross; Chen, Yi Charlie

    2016-01-01

    The dried root of Baikal skullcap (Scutellaria baicalensis) has been historically and widely used in traditional Eastern medicine. Modern science proved that baicalin is the major bioactive responsible for the physiological activity of Baikal skullcap. Baicalin, a flavonoid found in several species in the genus Scutellaria, has been regarded as a potent anticancer agent. In this review, we present the main extraction methods, anticancer activity and bioavailability of baicalin. Besides, the utilization of nanotechnology to improve the bioavailability of baicalin is also mentioned.

  9. The Molecular Mechanism of HDAC Inhibitors in Anticancer Effects

    Institute of Scientific and Technical Information of China (English)

    Gaofeng Bi; Guosheng Jiang

    2006-01-01

    HDACs and HATs are two kinds of enzymes which catalyse deacetylation and acetylation of histone in eukaryotes,whose dynamic balance has accurate regulation for gene transcription and gene expression of eukaryotes at DNA level. Disbalance of them can bring the disorder of proliferation and differentiation in normal cells, and then lead to the initiation of tumor. Their aberrant functions were directly related to the initiation and progression of various tumors, such as promyelocytic leukemia, Hodgkin lymphoma, colonic cancer and gastral cancer. The inhibitors of HDACs are used for treatment of tumor. They can restrain the activity of HDACs and block the inhibition of gene expression caused by the disorder of deacetylation. Its major biological effects lie in inducing differentiation of tumor cells, arresting cell circle at G0/G1, activating cell apoptosis gene, enhancing the sensitivity of chemical therapy and radioactive therapy. So far HDAC has been an important target enzyme in anticancer drug research.Cellular & Molecular Immunology. 2006;3(4):285-290.

  10. 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.

  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

    2016-05-26

    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.

  12. Anti-Cancer Effect of Lambertianic Acid by Inhibiting the AR in LNCaP Cells

    Directory of Open Access Journals (Sweden)

    Myoung-Sun Lee

    2016-07-01

    Full Text Available Lambertianic acid (LA is known to have anti-allergic and antibacterial effects. However, the anticancer activities and mechanism of action of LA have not been investigated. Therefore, the anticancer effects and mechanism of LA are investigated in this study. LA decreased not only AR protein levels, but also cellular and secretory levels of PSA. Furthermore, LA inhibited nuclear translocation of the AR induced by mibolerone. LA suppressed cell proliferation by inducing G1 arrest, downregulating CDK4/6 and cyclin D1 and activating p53 and its downstream molecules, p21 and p27. LA induced apoptosis and the expression of related proteins, including cleaved caspase-9 and -3, c-PARP and BAX, and inhibited BCl-2. The role of AR in LA-induced apoptosis was assessed by using siRNA. Collectively, these findings suggest that LA exerts the anticancer effect by inhibiting AR and is a valuable therapeutic agent in prostate cancer treatment.

  13. Anticancer Effects of Rosemary (Rosmarinus officinalis L.) Extract and Rosemary Extract Polyphenols

    Science.gov (United States)

    Moore, Jessy; Yousef, Michael; Tsiani, Evangelia

    2016-01-01

    Cancer cells display enhanced growth rates and a resistance to apoptosis. The ability of cancer cells to evade homeostasis and proliferate uncontrollably while avoiding programmed cell death/apoptosis is acquired through mutations to key signaling molecules, which regulate pathways involved in cell proliferation and survival. Compounds of plant origin, including food components, have attracted scientific attention for use as agents for cancer prevention and treatment. The exploration into natural products offers great opportunity to evaluate new anticancer agents as well as understand novel and potentially relevant mechanisms of action. Rosemary extract has been reported to have antioxidant, anti-inflammatory, antidiabetic and anticancer properties. Rosemary extract contains many polyphenols with carnosic acid and rosmarinic acid found in highest concentrations. The present review summarizes the existing in vitro and in vivo studies focusing on the anticancer effects of rosemary extract and the rosemary extract polyphenols carnosic acid and rosmarinic acid, and their effects on key signaling molecules. PMID:27869665

  14. Anticancer Effects of Rosemary (Rosmarinus officinalis L. Extract and Rosemary Extract Polyphenols

    Directory of Open Access Journals (Sweden)

    Jessy Moore

    2016-11-01

    Full Text Available Cancer cells display enhanced growth rates and a resistance to apoptosis. The ability of cancer cells to evade homeostasis and proliferate uncontrollably while avoiding programmed cell death/apoptosis is acquired through mutations to key signaling molecules, which regulate pathways involved in cell proliferation and survival. Compounds of plant origin, including food components, have attracted scientific attention for use as agents for cancer prevention and treatment. The exploration into natural products offers great opportunity to evaluate new anticancer agents as well as understand novel and potentially relevant mechanisms of action. Rosemary extract has been reported to have antioxidant, anti-inflammatory, antidiabetic and anticancer properties. Rosemary extract contains many polyphenols with carnosic acid and rosmarinic acid found in highest concentrations. The present review summarizes the existing in vitro and in vivo studies focusing on the anticancer effects of rosemary extract and the rosemary extract polyphenols carnosic acid and rosmarinic acid, and their effects on key signaling molecules.

  15. Synthesis and anticancer effects of 6-nitro-4-anilinoquinazolines and 6-amino-4-anilinoquinazolines

    Institute of Scientific and Technical Information of China (English)

    孙晓莉; 刘志红; 陈惠; 张生勇; 药立波

    2003-01-01

    Objective: To synthesize inhibitors of the epidermal growth factor receptor tyrosine kinase such as 6-nitro-4-anilinoquinazolines and 6-amino-4-anilinoquinazolines,and to compare their anticancer effects in vitro. Methods: The 4-anilinoquinazolines compounds were prepared by hydrolyzed, ringed, halagenated, substituded in turn from 2-amino-5-nitrobenzylcarbonitril. The synthesized 4- anilinoquinazoline compounds has been rudimentarily screened by using A431 tumor cell line which overexpresses epidermal growth factor receptor as model adopted MTT method. Results: Five 6-nitro-4-halo-sbstituted anilinoquinazolines and five 6-amino-4-halo-substituted anilinoquinazolines have been obtained,and all of them had anticancer activity. The anticancer activity of 6-amino substituted inhibitors was higher than that of 6-nitro substituted inhibitors. However, the difference of anticancer activity between two series of quinazoline was much less than that of their inhibiting EGFR tyrosine kinase activity. Conclusion: The probable reason for 6-nitro-4-anilinoquinazolines having anticancer activity in vitro was that they had been partially transformed to 6-amino-4-anilinoquinazolines through endocellular cytochrome oxidation-reduction system.

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

    Science.gov (United States)

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

    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 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.

  17. 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.

  18. Telomerase inhibitory effects of medicinal mushrooms and lichens, and their anticancer activity.

    Science.gov (United States)

    Xu, Baojun; Li, Chantian; Sung, Changkeun

    2014-01-01

    Telomerase has been widely accepted as a cancer marker and a promising therapeutic target for novel anticancer drugs. The aim of this study was to investigate the in vitro telomerase inhibitory effects of mushrooms and their anticancer properties. The inhibitory effects of mushrooms and lichens against telomerase activity of HL-60 cells were systematically assessed using polymerase chain reaction based on assay of telomeric repeat amplification protocol. Telomerase inhibitory samples were further tested for antiproliferation effects against the gastric cell line SNU-1 using the MTT method. Ethyl acetate extract of Pleurotus ostreatus, ethyl acetate and water extracts of Lasiosphaera fenzlii, hexane extract of Strobilomyces floccopus, water extract of Sarcodon aspratus, and hexane, ethyl acetate, and water extracts from Umbilicaria esculenta showed strong positive telomerase inhibitory activity. Hexane extract of S. floccopus and water extracts from the edible lichen U. esculenta exhibited strong anticancer effects against SNU-1 cells through antiproliferation assay. The water extract of U. esculenta has a great potential to be developed into an anticancer agent that targets telomerase.

  19. Anti-cancer effects of traditional Korean wild vegetables in complementary and alternative medicine.

    Science.gov (United States)

    Ju, Hyun-Mok; Yu, Kwang-Won; Cho, Sung-Dae; Cheong, Sun Hee; Kwon, Ki Han

    2016-02-01

    This research study explored the anti-cancer effects of natural materials in South Korea. Although South Korea has a long history of traditional medicine, many natural materials of South Korea have not yet been introduced to the rest of the world because of language barriers and inconsistent study conditions. In the past 3 years, 56 papers introducing 56 natural materials, which have anti-cancer effects, have been published by scientists in South Korea. Further, these studies have introduced five kinds of natural materials presented in research papers that were written in Korean and are therefore virtually unknown overseas. The anti-cancer effects were confirmed by 2-3 cancer markers in the majority of the studies, with the most common targets being breast cancer cells and gastric cancer cells. These cancers have the greatest incidence in South Korea. The natural materials studied not only exhibit anti-cancer activity but also display anti-inflammatory, anti-oxidative stress, and anti-diabetic activities. They have not yet been used for the direct treatment of disease but have potential as medicinal materials for alternative and complementary medicine for the treatment of many modern diseases. Many natural materials of South Korea are already known all over the world, and with this study, we hope to further future research to learn more about these natural medicines.

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

    Directory of Open Access Journals (Sweden)

    Sasipawan Machana

    2012-08-01

    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.

  1. Anticancer effects of deproteinized asparagus polysaccharide on hepatocellular carcinoma in vitro and in vivo.

    Science.gov (United States)

    Xiang, Jianfeng; Xiang, Yanjie; Lin, Shengming; Xin, Dongwei; Liu, Xiaoyu; Weng, Lingling; Chen, Tao; Zhang, Minguang

    2014-04-01

    Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies in the world whose chemoprevention became increasingly important in HCC treatment. Although the anticancer effects of asparagus constituents have been investigated in several cancers, its effects on hepatocellular carcinoma have not been fully studied. In this study, we investigated the anticancer effects of the deproteinized asparagus polysaccharide on the hepatocellular carcinoma cells using the in vitro and in vivo experimental model. Our data showed that deproteinized asparagus polysaccharide might act as an effective inhibitor on cell growth in vitro and in vivo and exert potent selective cytotoxicity against human hepatocellular carcinoma Hep3B and HepG2 cells. Further study showed that it could potently induce cell apoptosis and G2/M cell cycle arrest in the more sensitive Hep3B and HepG2 cell lines. Moreover, deproteinized asparagus polysaccharide potentiated the effects of mitomycin both in vitro and in vivo. Mechanistic studies revealed that deproteinized asparagus polysaccharide might exert its activity through an apoptosis-associated pathway by modulating the expression of Bax, Bcl-2, and caspase-3. In conclusion, deproteinized asparagus polysaccharide exhibited significant anticancer activity against hepatocellular carcinoma cells and could sensitize the tumoricidal effects of mitomycin, indicating that it is a potential therapeutic agent (or chemosensitizer) for liver cancer therapy.

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

    OpenAIRE

    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 of CAM is considered as safe. However, concomitant use of CAM and anticancer drugs could result in serious safety issues since CAM have the potential to cause pharmacokinetic interactions with conv...

  3. 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.

  4. Anticancer peptides from bacteria

    Directory of Open Access Journals (Sweden)

    Tomasz M. Karpiński

    2013-08-01

    Full Text Available Cancer is a leading cause of death in the world. The rapid development of medicine and pharmacology allows to create new and effective anticancer drugs. Among modern anticancer drugs are bacterial proteins. Until now has been shown anticancer activity among others azurin and exotoxin A from Pseudomonas aeruginosa, Pep27anal2 from Streptococcus pneumoniae, diphtheria toxin from Corynebacterium diphtheriae, and recently discovered Entap from Enterococcus sp. The study presents the current data regarding the properties, action and anticancer activity of listed peptides.

  5. Synergistic anticancer effects of triptolide and celastrol, two main compounds from thunder god vine.

    Science.gov (United States)

    Jiang, Qi-Wei; Cheng, Ke-Jun; Mei, Xiao-Long; Qiu, Jian-Ge; Zhang, Wen-Ji; Xue, You-Qiu; Qin, Wu-Ming; Yang, Yang; Zheng, Di-Wei; Chen, Yao; Wei, Meng-Ning; Zhang, Xu; Lv, Min; Chen, Mei-Wan; Wei, Xing; Shi, Zhi

    2015-10-20

    Triptolide and celastrol are two main active compounds isolated from Thunder God Vine with the potent anticancer activity. However, the anticancer effect of triptolide in combination with celastrol is still unknown. In the present study, we demonstrated that the combination of triptolide with celastrol synergistically induced cell growth inhibition, cell cycle arrest at G2/M phase and apoptosis with the increased intracellular ROS accumulation in cancer cells. Pretreatment with ROS scavenger N-acetyl-L-cysteine dramatically blocked the apoptosis induced by co-treatment with triptolide and celastrol. Treatment with celastrol alone led to the decreased expressions of HSP90 client proteins including survivin, AKT, EGFR, which was enhanced by the addition of triptolide. Additionally, the celastrol-induced expression of HSP70 and HSP27 was abrogated by triptolide. In the nude mice with xenograft tumors, the lower-dose combination of triptolide with celastrol significantly inhibited the growth of tumors without obvious toxicity. Overall, triptolide in combination with celastrol showed outstanding synergistic anticancer effect in vitro and in vivo, suggesting that this beneficial combination may offer a promising treatment option for cancer patients.

  6. [Effect of diazepam on delayed nausea and vomiting caused by anticancer agents].

    Science.gov (United States)

    Tong, F Z; Zhang, J Q; Qiao, X M; Mao, Y C; Meng, F Y; Liu, H J; Hui, S; Zhu, F X; Shu, W; Hong, J

    1998-02-01

    We conducted an evaluation of the usefulness of antiemetics (5-Hydroxy-tryptamine 3 receptor antagonism, 5HT3RA) combined with diazepam for delayed nausea and vomiting due to anticancer agents in 17 patients with various malignancies (such as lung Ca, breast Ca, esophagus Ca, gastric Ca, colon Ca, and non Hodgkin's disease) for whom chemotherapy was performed with different regimens in the Dept. of Oncologic Chemotherapy, People's Hospital, Beijing Medical University. Antiemetics (5HT3RA) combined with diazepam were given only to cases that had symptoms of nausea and vomiting induced by anticancer agents in the 1st course and invalidity with antiemetics (5HT3RA) alone in this study. Antiemetic (5HT3RA) agents + Dexamethasone were dosed before chemotherapy and also diazepam 5 mg orally after 24 hours (namely, when nausea was observed). Nausea was reduced and vomiting decreased after the antiemetic treatment with 5HT3RA + Dexamethasone and diazepam. These results indicated that 5HT3RA and diazepam combination therapies were more effective than 5HT3 RA + Dexamethasone alone for delayed nausea and vomiting. Further, the antiemetics had characters that a short adminiter time, few times and a take not over dose. The only side effect related to this antiemetic therapy was light somnolence. Antiemetics combined with diazepam might be a useful therapy against delayed nausea and vomiting induced by anticancer agents.

  7. Characterization of Polysaccharide by HPLC: Extraction and Anticancer Effects

    OpenAIRE

    Liming Gao; Ya Di; Jiandong Wu; Ming Shi; Fulu Zheng

    2014-01-01

    Cervical cancer is a serious health hazard for women’s reproductive system cancer; the method of treatment for cervical cancer is still in surgery, chemotherapy, and radiotherapy as the basic means, but with many complications. The effects of natural medicines for cervical cancer are increasingly becoming the focus of people’s attentions. By studying the polysaccharide of cervical cancer in mice, we found that shark cartilage polysaccharide can increase the serum levels of T-SOD and GSH and d...

  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. 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

    2015-12-15

    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.

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

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    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.

  11. 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.

  12. 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.

  13. PST-Gold nanoparticle as an effective anticancer agent with immunomodulatory properties.

    Science.gov (United States)

    Joseph, Manu M; Aravind, S R; Varghese, Sheeja; Mini, S; Sreelekha, T T

    2013-04-01

    Polysaccharide PST001, which is isolated from the seed kernels of Tamarindus indica (Ti), is an antitumor and immunomodulatory compound. Gold nanoparticles have been used for various applications in cancer. In the present report, a novel strategy for the synthesis and stabilization of gold nanoparticles using anticancer polysaccharide PST001 was employed and the nanoparticles' antitumor activity was evaluated. PST-Gold nanoparticles were prepared such that PST001 acted both as a reducing agent and as a capping agent. PST-Gold nanoparticles showed high stability, no obvious aggregation for months and a wide range of pH tolerance. PST-Gold nanoparticles not only retained the antitumor effect of PST001 but also showed an enhanced effect even at a low concentration. It was also found that the nanoparticles exerted their antitumor effects through the induction of apoptosis. In vivo assays on BALB/c mice revealed that PST-Gold nanoparticles exhibited immunomodulatory effects. Evaluation of biochemical, hematological and histopathological features of mice revealed that PST-Gold nanoparticles could be administered safely without toxicity. Using the polysaccharide PST001 for the reduction and stabilization of gold nanoparticles does not introduce any environmental toxicity or biological hazards, and these particles are more effective than the parent polysaccharide. Further studies should be employed to exploit these particles as anticancer agents with imaging properties.

  14. 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.

  15. Anticancer effect of xanthohumol induces growth inhibition and apoptosis of human liver cancer through NF-κB/p53-apoptosis signaling pathway

    OpenAIRE

    ZHAO, XIANGQIAN; Jiang, Kai; Liang, Bin; Huang, Xiaoqiang

    2015-01-01

    Xanthohumol may prevent and cure diabetes and atherosis, have oxidation resistance and antiviral function as well as anticancer effect preventing cancer cell metastasis. We investigate whether the anticancer effect of xanthohumol induces growth inhibition and apoptosis of human liver cancer through NF-κB/p53-apoptosis signaling pathway. Human liver cancer HepG2 cell were treated with 10, 20, 30 and 40 µM xanthohumol for 48 h. The present study showed that the anticancer effect of xanthohumol ...

  16. Anti-cancer effects of Kochia scoparia fruit in human breast cancer cells

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    Hye-Yeon Han

    2014-01-01

    Full Text Available Background: The fruit of Kochia scoparia Scharder is widely used as a medicinal ingredient for the treatment of dysuria and skin diseases in China, Japan and Korea. Especially, K. scoparia had been used for breast masses and chest and flank pain. Objective: To investigate the anti-cancer effect of K. scoparia on breast cancer. Materials and Methods: We investigated the anti-cancer effects of K. scoparia, methanol extract (MEKS in vitro. We examined the effects of MEKS on the proliferation rate, cell cycle arrest, reactive oxygen species (ROS generation and activation of apoptosis-associated proteins in MDA-MB-231, human breast cancer cells. Results: MTT assay results demonstrated that MEKS decreased the proliferation rates of MDA-MB-231 cells in a dose-dependent manner with an IC 50 value of 36.2 μg/ml. MEKS at 25 μg/ml significantly increased the sub-G1 DNA contents of MDA-MB-231 cells to 44.7%, versus untreated cells. In addition, MEKS induced apoptosis by increasing the levels of apoptosis-associated proteins such as cleaved caspase 3, cleaved caspase 8, cleaved caspase 9 and cleaved Poly (ADP-ribose polymerase (PARP. Conclusion: These results suggest that MEKS inhibits cell proliferation and induces apoptosis in breast cancer cells and that MEKS may have potential chemotherapeutic value for the treatment of human breast cancer.

  17. In Vitro and in Vivo Antitumoral Effects of Combinations of Polyphenols, or Polyphenols and Anticancer Drugs: Perspectives on Cancer Treatment

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    Massimo Fantini

    2015-04-01

    Full Text Available Carcinogenesis is a multistep process triggered by genetic alterations that activate different signal transduction pathways and cause the progressive transformation of a normal cell into a cancer cell. Polyphenols, compounds ubiquitously expressed in plants, have anti-inflammatory, antimicrobial, antiviral, anticancer, and immunomodulatory properties, all of which are beneficial to human health. Due to their ability to modulate the activity of multiple targets involved in carcinogenesis through direct interaction or modulation of gene expression, polyphenols can be employed to inhibit the growth of cancer cells. However, the main problem related to the use of polyphenols as anticancer agents is their poor bioavailability, which might hinder the in vivo effects of the single compound. In fact, polyphenols have a poor absorption and biodistribution, but also a fast metabolism and excretion in the human body. The poor bioavailability of a polyphenol will affect the effective dose delivered to cancer cells. One way to counteract this drawback could be combination treatment with different polyphenols or with polyphenols and other anti-cancer drugs, which can lead to more effective antitumor effects than treatment using only one of the compounds. This report reviews current knowledge on the anticancer effects of combinations of polyphenols or polyphenols and anticancer drugs, with a focus on their ability to modulate multiple signaling transduction pathways involved in cancer.

  18. In vitro and in vivo antitumoral effects of combinations of polyphenols, or polyphenols and anticancer drugs: perspectives on cancer treatment.

    Science.gov (United States)

    Fantini, Massimo; Benvenuto, Monica; Masuelli, Laura; Frajese, Giovanni Vanni; Tresoldi, Ilaria; Modesti, Andrea; Bei, Roberto

    2015-04-24

    Carcinogenesis is a multistep process triggered by genetic alterations that activate different signal transduction pathways and cause the progressive transformation of a normal cell into a cancer cell. Polyphenols, compounds ubiquitously expressed in plants, have anti-inflammatory, antimicrobial, antiviral, anticancer, and immunomodulatory properties, all of which are beneficial to human health. Due to their ability to modulate the activity of multiple targets involved in carcinogenesis through direct interaction or modulation of gene expression, polyphenols can be employed to inhibit the growth of cancer cells. However, the main problem related to the use of polyphenols as anticancer agents is their poor bioavailability, which might hinder the in vivo effects of the single compound. In fact, polyphenols have a poor absorption and biodistribution, but also a fast metabolism and excretion in the human body. The poor bioavailability of a polyphenol will affect the effective dose delivered to cancer cells. One way to counteract this drawback could be combination treatment with different polyphenols or with polyphenols and other anti-cancer drugs, which can lead to more effective antitumor effects than treatment using only one of the compounds. This report reviews current knowledge on the anticancer effects of combinations of polyphenols or polyphenols and anticancer drugs, with a focus on their ability to modulate multiple signaling transduction pathways involved in cancer.

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

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    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.

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

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    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.

  1. The Anticancer Effect of Fucoidan in PC-3 Prostate Cancer Cells

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    Hee-Kyoung Kang

    2013-08-01

    Full Text Available Fucoidan, a sulfated polysaccharide, has a variety of biological activities, such as anti-cancer, anti-angiogenic and anti-inflammatory. However, the mechanisms of action of fucoidan as an anti-cancer agent have not been fully elucidated. The present study examined the anti-cancer effect of fucoidan obtained from Undaria pinnatifida in PC-3 cells, human prostate cancer cells. Fucoidan induced the apoptosis of PC-3 cells by activating both intrinsic and extrinsic pathways. The induction of apoptosis was accompanied by the activation of extracellular signal-regulated kinase mitogen-activated protein kinase (ERK1/2 MAPK and the inactivation of p38 MAPK and phosphatidylinositol 3-kinase (PI3K/Akt. In addition, fucoidan also induced the up-regulation of p21Cip1/Waf and down-regulation of E2F-1 cell-cycle-related proteins. Furthermore, in the Wnt/β-catenin pathway, fucoidan activated GSK-3β that resulted in the decrease of β-catenin level, followed by the decrease of c-myc and cyclin D1 expressions, target genes of β-catenin in PC-3 cells. These results suggested that fucoidan treatment could induce intrinsic and extrinsic apoptosis pathways via the activation of ERK1/2 MAPK, the inactivation of p38 MAPK and PI3K/Akt signaling pathway, and the down-regulation of Wnt/β-catenin signaling pathway in PC-3 prostate cancer cells. These data support that fucoidan might have potential for the treatment of prostate cancer.

  2. Comparative anticancer effects of flavonoids and diazepam in cultured cancer cells.

    Science.gov (United States)

    Kim, Dae-Hyun; Lee, Jae-Tae; Lee, In-Kyu; Ha, Jeoung-Hee

    2008-02-01

    This study examined the comparative anticancer effects of flavonoids and diazepam in the cultured cancer cells. In the SNU-C4 colorectal and MDA-MB-231 breast adenocarcinoma cells, apigenin and fisetin, flavonoids, and diazepam inhibited cancer cell survival concentration and incubation-time dependently. Diazepam consistently inhibited FAS activity, a known anticancer mechanism of flavonoids, in a concentration dependent manner. Unlike diazepam, in highly aggressive breast MDA-MB-231 cells known to have a nuclear/perinuclear located PBR, PK11195, a specific PBR ligand enhanced the proliferation of cells, and the proliferative effect of PK11195 was reversed by an addition of lovastatin, a HMG-CoA reductase inhibitor. Diazepam- and flavonoids-induced cytotoxic activity in both cancer cell lines was not reduced by the addition of 5-fluorouracil (5-FU), a chemotherapeutic agent. Like flavonoids, diazepam inhibited the release of vascular endothelial growth factor (VEGF) and granulocyte-macrophage-colony stimulating factor (GM-CSF) into supernatants of cultured in the SNU-C4 and MDA-MB-231 cells. In conclusion, this study provided in vitro information on the safe use of sedative in oncologic patients.

  3. 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.

  4. Genome-wide transcriptional effects of the anti-cancer agent camptothecin.

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    Artur Veloso

    Full Text Available The anti-cancer drug camptothecin inhibits replication and transcription by trapping DNA topoisomerase I (Top1 covalently to DNA in a "cleavable complex". To examine the effects of camptothecin on RNA synthesis genome-wide we used Bru-Seq and show that camptothecin treatment primarily affected transcription elongation. We also observed that camptothecin increased RNA reads past transcription termination sites as well as at enhancer elements. Following removal of camptothecin, transcription spread as a wave from the 5'-end of genes with no recovery of transcription apparent from RNA polymerases stalled in the body of genes. As a result, camptothecin preferentially inhibited the expression of large genes such as proto-oncogenes, and anti-apoptotic genes while smaller ribosomal protein genes, pro-apoptotic genes and p53 target genes showed relative higher expression. Cockayne syndrome group B fibroblasts (CS-B, which are defective in transcription-coupled repair (TCR, showed an RNA synthesis recovery profile similar to normal fibroblasts suggesting that TCR is not involved in the repair of or RNA synthesis recovery from transcription-blocking Top1 lesions. These findings of the effects of camptothecin on transcription have important implications for its anti-cancer activities and may aid in the design of improved combinatorial treatments involving Top1 poisons.

  5. Anticancer properties of Monascus metabolites.

    Science.gov (United States)

    Yang, Tao; Liu, Junwen; Luo, Feijun; Lin, Qinlu; Rosol, Thomas J; Deng, Xiyun

    2014-08-01

    This review provides up-to-date information on the anticancer properties of Monascus-fermented products. Topics covered include clinical evidence for the anticancer potential of Monascus metabolites, bioactive Monascus components with anticancer potential, mechanisms of the anticancer effects of Monascus metabolites, and existing problems as well as future perspectives. With the advancement of related fields, the development of novel anticancer Monascus food products and/or pharmaceuticals will be possible with the ultimate goal of decreasing the incidence and mortality of malignancies in humans.

  6. Anticancer Properties of PPARα-Effects on Cellular Metabolism and Inflammation

    Directory of Open Access Journals (Sweden)

    Maja Grabacka

    2008-01-01

    Full Text Available Peroxisome proliferator-activated receptors (PPARs have lately attracted much attention as therapeutic targets. Previously, PPAR ligands were associated with the treatment of diabetes, hyperlipidemia and cardiovascular diseases, as they modulate the expression of genes regulating glucose and lipid metabolism. Recently, PPAR ligands have been also considered as potential anticancer agents, with relatively low systemic toxicity. The emerging evidence for antiproliferative, proapoptotic, antiinflammatory and potential antimetastatic properties of PPARα ligands prompted us to discuss possible roles of PPARα in tumor suppression. PPARα activation can target cancer cells energy balance by blocking fatty acid synthesis and by promoting fatty acid β-oxidation. In the state of limited nutrient availability, frequently presents in the tumor microenvironment, PPARα cooperates with AMP-dependent protein kinase in: (i repressing oncogenic Akt activity, (ii inhibiting cell proliferation, and (iii forcing glycolysis-dependent cancer cells into “metabolic catastrophe.” Other potential anticancer effects of PPARα include suppression of inflammation, and upregulation of uncoupling proteins (UCPs, which attenuates mitochondrial reactive oxygen species production and cell proliferation. In conclusion, there are strong premises that the low-toxic and well-tolerated PPAR ligands should be considered as new therapeutic agents to fight disseminating cancer, which represents the major challenge for modern medicine and basic research.

  7. Anticancer Properties of PPARalpha-Effects on Cellular Metabolism and Inflammation.

    Science.gov (United States)

    Grabacka, Maja; Reiss, Krzysztof

    2008-01-01

    Peroxisome proliferator-activated receptors (PPARs) have lately attracted much attention as therapeutic targets. Previously, PPAR ligands were associated with the treatment of diabetes, hyperlipidemia and cardiovascular diseases, as they modulate the expression of genes regulating glucose and lipid metabolism. Recently, PPAR ligands have been also considered as potential anticancer agents, with relatively low systemic toxicity. The emerging evidence for antiproliferative, proapoptotic, antiinflammatory and potential antimetastatic properties of PPARalpha ligands prompted us to discuss possible roles of PPARalpha in tumor suppression. PPARalpha activation can target cancer cells energy balance by blocking fatty acid synthesis and by promoting fatty acid beta-oxidation. In the state of limited nutrient availability, frequently presents in the tumor microenvironment, PPARalpha cooperates with AMP-dependent protein kinase in: (i) repressing oncogenic Akt activity, (ii) inhibiting cell proliferation, and (iii) forcing glycolysis-dependent cancer cells into "metabolic catastrophe." Other potential anticancer effects of PPARalpha include suppression of inflammation, and upregulation of uncoupling proteins (UCPs), which attenuates mitochondrial reactive oxygen species production and cell proliferation. In conclusion, there are strong premises that the low-toxic and well-tolerated PPAR ligands should be considered as new therapeutic agents to fight disseminating cancer, which represents the major challenge for modern medicine and basic research.

  8. 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

  9. How strong is the edge effect in the adsorption of anticancer drugs on a graphene cluster?

    Science.gov (United States)

    Rungnim, Chompoonut; Chanajaree, Rungroj; Rungrotmongkol, Thanyada; Hannongbua, Supot; Kungwan, Nawee; Wolschann, Peter; Karpfen, Alfred; Parasuk, Vudhichai

    2016-04-01

    The adsorption of nucleobase-analog anticancer drugs (fluorouracil, thioguanine, and mercaptopurine) on a graphene flake (C54H18) was investigated by shifting the site at which adsorption occurs from one end of the sheet to the other end. The counterpoise-corrected M06-2X/cc-pVDZ binding energies revealed that the binding stability decreases in the sequence thioguanine > mercaptopurine > fluorouracil. We found that adsorption near the middle of the sheet is more favorable than adsorption near the edge due to the edge effect. This edge effect is stronger for the adsorption of thioguanine or mercaptopurine than for fluorouracil adsorption. However, the edge effect reduces the binding energy of the drug to the flake by only a small amount, <5 kcal/mol, depending on the adsorption site and the alignment of the drug at this site.

  10. Hydroxycamptothecin-loaded nanoparticles enhance target drug delivery and anticancer effect

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    Li Su

    2008-05-01

    Full Text Available Abstract Background Hydroxycamptothecin (HCPT has been shown to have activity against a broad spectrum of cancers. In order to enhance its tissue-specific delivery and anticancer activity, we prepared HCPT-loaded nanoparticles made from poly(ethylene glycol-poly(γ-benzyl-L-glutamate (PEG-PBLG, and then studied their release characteristics, pharmacokinetic characteristics, and anticancer effects. PEG-PBLG nanoparticles incorporating HCPT were prepared by a dialysis method. Scanning electron microscopy (SEM was used to observe the shape and diameter of the nanoparticles. The HCPT release characteristics in vitro were evaluated by ultraviolet spectrophotometry. A high-performance liquid chromatography (HPLC detection method for determining HCPT in rabbit plasma was established. The pharmacokinetic parameters of HCPT/PEG-PBLG nanoparticles were compared with those of HCPT. Results The HCPT-loaded nanoparticles had a core-shell spherical structure, with a core diameter of 200 nm and a shell thickness of 30 nm. Drug-loading capacity and drug encapsulation were 7.5 and 56.8%, respectively. The HCPT release profile was biphasic, with an initial abrupt release, followed by sustained release. The terminal elimination half-lives (t 1/2 β of HCPT and HCPT-loaded nanoparticles were 4.5 and 10.1 h, respectively. Peak concentrations (Cmax of HCPT and HCPT-loaded nanoparticles were 2627.8 and 1513.5 μg/L, respectively. The apparent volumes of distribution of the HCPT and HCPT-loaded nanoparticles were 7.3 and 20.0 L, respectively. Compared with a blank control group, Lovo cell xenografts or Tca8113 cell xenografts in HCPT or HCPT-loaded nanoparticle treated groups grew more slowly and the tumor doubling times were increased. The tumor inhibition effect in the HCPT-loaded nanosphere-treated group was significantly higher than that of the HCPT-treated group (p 0.05. Conclusion Compared to the HCPT- and control-treated groups, the HCPT-loaded nanoparticle

  11. Sesamin synergistically potentiates the anticancer effects of γ-tocotrienol in mammary cancer cell lines.

    Science.gov (United States)

    Akl, Mohamed R; Ayoub, Nehad M; Abuasal, Bilal S; Kaddoumi, Amal; Sylvester, Paul W

    2013-01-01

    γ-Tocotrienol and sesamin are phytochemicals that display potent anticancer activity. Since sesamin inhibits the metabolic degradation of tocotrienols, studies were conducted to determine if combined treatment with sesamin potentiates the antiproliferative effects of γ-tocotrienol on neoplastic mouse (+SA) and human (MCF-7 and MDA-MB-231) mammary cancer cells. Results showed that treatment with γ-tocotrienol or sesamin alone induced a significant dose-responsive growth inhibition, whereas combination treatment with these agents synergistically inhibited the growth of +SA, MCF-7 and MDA-MB-231 mammary cancer cells, while similar treatment doses were found to have little or no effect on normal (mouse CL-S1 and human MCF-10A) mammary epithelial cell growth or viability. However, sesamin synergistic enhancement of γ-tocotrienol-induced anticancer effects was not found to be mediated from a reduction in γ-tocotrienol metabolism. Rather, combined treatment with subeffective doses of γ-tocotrienol and sesamin was found to induce G1 cell cycle arrest, and a corresponding decrease in cyclin D1, CDK2, CDK4, CDK6, phospho-Rb, and E2F1 levels, and increase in p27 and p16 levels. Additional studies showed that the antiproliferative effect of combination treatment did not initiate apoptosis or result in a decrease in mammary cancer cell viability. Taken together, these findings indicate that the synergistic antiproliferative action of combined γ-tocotrienol and sesamin treatment in mouse and human mammary cancer cells is cytostatic, not cytotoxic, and results from G1 cell cycle arrest.

  12. 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.

  13. Assessment of anticancer effect of chlorin e6 dimethyl ether for photodynamic therapy

    Directory of Open Access Journals (Sweden)

    M. A. Kaplan

    2014-01-01

    Full Text Available Results of the study for anticancer efficacy of photodynamic therapy with chlorin e6 dimethyl ether for treatment of outbread rats with sarcoma M-1 are represented. The drug was given intravenously or intraperitonealy at a dose of 1.25 mg/kg body weight (light dose – 300 J/cm2 or 2,5 mg/kg body weight (light dose – 150 J/cm2. The spectrometry showed that maximal drug accumulation in tumor was in 2 h after intravenous injection or 3 h after intraperitoneal injection of photosensitizer, thus, sensitized tumors were irradiated according to these time intervals. Intraperitoneal injection of chlorin е6 dimethyl ether at a dose of 1.25 mg/kg body weight with treatment session in 3 h and light dose of 300 J/cm2 was the most effective (the complete response in animals – 86%.

  14. 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.

  15. Cell type-specific anti-cancer properties of valproic acid: independent effects on HDAC activity and Erk1/2 phosphorylation

    DEFF Research Database (Denmark)

    Gotfryd, Kamil; Skladchikova, Galina; Lepekhin, Eugene E

    2010-01-01

    ABSTRACT: BACKGROUND: The anti-epileptic drug valproic acid (VPA) has attracted attention as an anti-cancer agent. Methods: The present study investigated effects of VPA exposure on histone deacetylase (HDAC) inhibition, cell growth, cell speed, and the degree of Erk1/2 phosphorylation in 10 cell....../2 phosphorylation are also important for the anti-cancer properties of VPA....

  16. 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.

  17. Anticancer and apoptosis-inducing effects of Moringa concanensis using hepG2 cell lines

    Directory of Open Access Journals (Sweden)

    V. Balamurugan

    2014-12-01

    Full Text Available The objective of the present investigation is focused on the anticancer activity of the ethanolic crude extract of Moringa concanensis leaf and bark against HepG2 cell line. The study was facilitated by collecting the plant sample and subjected to ethanol crude extraction. The anticancer activity of the crude extracted sample against HepG2 cell line was examined by MTT assay. The study confirms that the leaf crude extract of M. concanensis has pronounced anticancer potential against HepG2 cell lines while compared to that of the bark extract. The plant investigated possesses remarkable anticancer activity and hence isolation of the compound contributing to the activity may lead to develop at a novel and natural phytomedicine for the disease.

  18. Cell-based chip for the detection of anticancer effect on HeLa cells using cyclic voltammetry.

    Science.gov (United States)

    El-Said, Waleed Ahmed; Yea, Cheol-Heon; Kim, Hyunhee; Oh, Byung-Keun; Choi, Jeong-Woo

    2009-01-01

    HeLa cells directly immobilized on gold-patterned silicon substrate were used to assess the biological toxicity of anticancer drugs (hydroxyurea and cyclophosphamide). Immobilization of HeLa cells was confirmed by optical microscopy, and cell growth, viability and drug-related toxicity were examined by cyclic voltammetry and potentiometric stripping analysis. The voltammetric behaviors of HeLa cells displayed a quasi-reversible pattern with the peak current exhibiting a linear relationship with cell number. The attached living cells were exposed to different concentrations of hydroxyurea and cyclophosphamide as anticancer drugs, which induced the change of cyclic voltammetry current peak. As the exposed concentration of anticancer drugs was increased, the change of current peak was increased, which indicates the decrease of cell viability. Trypan Blue dyeing was performed to confirm the results of the effect of anticancer drugs on the cell viability which was obtained from cyclic voltammetry assay. The proposed direct cell immobilization method technique can be applied to the fabrication of cell chip for diagnosis, drug detection, and on-site monitoring.

  19. Synergistic anti-cancer effects of galangin and berberine through apoptosis induction and proliferation inhibition in oesophageal carcinoma cells.

    Science.gov (United States)

    Ren, Kewei; Zhang, Wenzhe; Wu, Gang; Ren, Jianzhuang; Lu, Huibin; Li, Zongming; Han, Xinwei

    2016-12-01

    Galangin is an active pharmacological ingredient from propolis and Alpinia officinarum Hance, and has been reported to have anti-cancer and antioxidative properties. Berberine, a major component of Berberis vulgaris extract, exhibits potent anti-cancer activities through distinct molecular mechanisms. However, the anticancer effect of galangin in combination with berberine is still unknown. In the present study, we demonstrated that the combination of galangin with berberine synergistically resulted in cell growth inhibition, apoptosis and cell cycle arrest at G2/M phase with the increased intracellular reactive oxygen species (ROS) levels in oesophageal carcinoma cells. Pretreatment with ROS scavenger promoted the apoptosis dramatically induced by co-treatment with galangin and berberine. Treatment with galangin and berberine alone caused the decreased expressions of Wnt3a and β-catenin. Interestingly, combination of galangin with berberine could further suppress Wnt3a and β-catenin expression and induce apoptosis in cancer cells. Additionally, in nude mice with xenograft tumors, the combinational treatment of galangin and berberine significantly inhibited the tumor growth without obvious toxicity. Overall, galangin in combination with berberine presented outstanding synergistic anticancer role in vitro and in vivo, indicating that the beneficial combination of galangin and berberine might provide a promising treatment for patients with oesophageal carcinoma.

  20. Anticancer effects of saponin and saponin-phospholipid complex of Panax notoginseng grown in Vietnam

    Institute of Scientific and Technical Information of China (English)

    Thu Dang Kim; Hai Nguyen Thanh; Duong Nguyen Thuy; Loi Vu Duc; Thu Vu Thi; Hung Vu Manh; Patcharee Boonsiri; Tung Bui Thanh

    2016-01-01

    Objective: To evaluate the antitumor activity both in vitro and in vivo of saponin–phospholipid complex of Panax notoginseng. Methods: The in vitro cytotoxic effect of saponins extract and saponin–phospholipid complex against human lung cancer NCI-H460 and breast cancer cell lines BT474 was examined using MTS assay. For in vivo evaluation of antitumor potential, saponin and saponin–phospholipid complex were administered orally in rats induced mammary carcinogenesis by 7,12-dimethylbenz(a)anthracene, for 30 days. Results: Our data showed that saponin–phospholipid complex had stronger anticancer effect compared to saponin extract. The IC50 values of saponin–phospholipid complex and saponin extract for NCI-H460 cell lines were 28.47μg/mL and 47.97μg/mL, respectively and these values for BT474 cells were 53.18μg/mL and 86.24μg/mL, respectively. In vivo experiments, administration of saponin, saponin–phospholipid complex and paclitaxel (positive control) effectively suppressed 7,12-dimethylbenz(a) anthracene-induced breast cancer evidenced by a decrease in tumor volume, the reduction of lipid peroxidation level and increase in the body weight, and elevated the enzymatic antioxidant activities of su-peroxide dismutase, catalase, glutathione peroxidase in rat breast tissue. Conclusions: Our study suggests that saponin extract from Panax notoginseng and saponin–phospholipid complex have potential to prevent cancer, especially breast cancer.

  1. 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.

  2. Alcoholic Extract of Eclipta alba Shows In Vitro Antioxidant and Anticancer Activity without Exhibiting Toxicological Effects

    Science.gov (United States)

    Arya, Rakesh Kumar; Dev, Kapil; Sharma, Chetan; Hossain, Zakir; Meena, Sanjeev; Arya, K. R.; Gayen, J. R.

    2017-01-01

    As per WHO estimates, 80% of people around the world use medicinal plants for the cure and prevention of various diseases including cancer owing to their easy availability and cost effectiveness. Eclipta alba has long been used in Ayurveda to treat liver diseases, eye ailments, and hair related disorders. The promising medicinal value of E. alba prompted us to study the antioxidant, nontoxic, and anticancer potential of its alcoholic extract. In the current study, we evaluated the in vitro cytotoxic and antioxidant effect of the alcoholic extract of Eclipta alba (AEEA) in multiple cancer cell lines along with control. We have also evaluated its effect on different in vivo toxicity parameters. Here, we found that AEEA was found to be most active in most of the cancer cell lines but it significantly induced apoptosis in human breast cancer cell lines by disrupting mitochondrial membrane potential and DNA damage. Moreover, AEEA treatment inhibited migration in both MCF 7 and MDA-MB-231 cells in a dose dependent manner. Further, AEEA possesses robust in vitro antioxidant activity along with high total phenolic and flavonoid contents. In summary, our results indicate that Eclipta alba has enormous potential in complementary and alternative medicine for the treatment of cancer. PMID:28250894

  3. Maturation of dendritic cells by pullulan promotes anti-cancer effect

    Science.gov (United States)

    Xu, Li; Zhang, LiJun; Yu, Qing; Jin, Jun-O

    2016-01-01

    Previous studies have demonstrated that pullulan, a polysaccharide purified from Aureobasidium pullulans, has immune-stimulatory effects on T and B cells. Moreover, pullulan has been used as a carrier in the delivery of the antigen (Ag) peptide to lymphoid tissues. However, the in vivo effect of pullulan on dendritic cells (DC) has not been well characterized. In this study, we assessed the effect of pullulan on DC activation and anti-cancer immunity. The results showed that the pullulan treatment up-regulated co-stimulatory molecule expression and enhanced pro-inflammatory cytokine production in bone marrow-derived DCs (BMDC) in vitro and in spleen DCs in vivo. Moreover, the combination of ovalbumin (OVA) and pullulan induced OVA antigen-specific T cell activations in vivo. In tumor-bearing mice, pullulan induced the maturation of DCs in spleen and tumor draining lymph node (drLN), and promoted the OVA-specific T cell activation and migration of the T cells into the tumor. In addition, the combination of OVA and pullulan inhibited B16-OVA tumor growth and liver metastasis. The combination of tyrosinase-related protein 2 (TRP2) peptide and pullulan treatment also suppressed B16 melanoma growth. Thus, the results demonstrated that pullulan enhanced DC maturation and function, and it acted as an adjuvant in promoting Ag-specific immune responses in mice. Thus, pullulan could be a new and useful adjuvant for use in therapeutic cancer vaccines. PMID:27341129

  4. Antioxidant, anticancer, and apoptosis-inducing effects of Piper extracts in HeLa cells

    Directory of Open Access Journals (Sweden)

    Wahyu Widowati

    2013-06-01

    Full Text Available Objective: Cervical cancer is the second most common cancer as well as one of leading cause of cancer-related death for women worldwide. In regards to that issue, focus of this paper will be on popularly used Piperaceae members including Piper betle L, Piper cf fragile Benth, Piper umbellatum L, Piper aduncum L, Piper pellucidum L. This research was conducted to elucidate the antioxidant, anticancer and apoptosis inducing activities of Piperaceae extracts on cervical cancer cells, namely HeLa cell line. Methods: The anticancer activity was determined by inhibiting the proliferation of cells. Apoptosis inducing was determined by inhibiting proliferation cells and by SubG1 flow cytometry. The antioxidant activity is determined by using superoxide dismutase value and 2,2-diphenyl-1-picrylhydrazyl (DPPH radical scavenging activity. Results: The highest anticancer activity at 24 h incubation was found for P.pellucidum extract (IC50: 2.85 µg/ml; The anticancer activity at 48 h incubation was more than at 24 h for all extracts. The highest apoptotic activity was found for P.betle (12.5 µg/ml at both 24 and 48 h incubatio. The highest antioxidant activity was also represented by P.betle extract. Conclusions: All Piperaceae extracts have high anticancer activity; longer incubation increase anticancer activity. P.betle extract has the highest antioxidant property. [J Exp Integr Med 2013; 3(3.000: 225-230

  5. Synthesis of N-Mannich bases of berberine linking piperazine moieties revealing anticancer and antioxidant effects

    Directory of Open Access Journals (Sweden)

    Bhupendra Mistry

    2017-01-01

    Full Text Available A new Mannich base series of piperazine linked berberine analogues was furnished in this study to screen the antioxidant and anticancer potential of the resultant analogues. Alkoxy group at a C-9 position of berberine was converted to hydroxyl functionality to enhance the ability of final scaffolds binding to the target of drug action mainly through hydrophobic effect, conjugation effect, whereas Mannich base functionality was introduced on the C-12 position of berberine. Scaffolds were investigated for their free radical scavenging antioxidant potential in FRAP and DPPH assay, whereas tested to check their Fe+3 reducing power in ABTS assay. The radical scavenging potential of the final derivatives 4a–j was found excellent with IC50s, 30 of therapeutic indices, thus exerting low cytotoxic values against Malin–Darby canine kidney (MDCK cell lines at CC50s >125 μg/mL. Hence, from the bioassay outcomes it can be stated that these analogues are dual active agents as the scavengers of reactive oxygen species and inhibitors of the cancerous cells as compounds with halogen functional group have overall good pharmacological potential in assays studied in this research. Correct structure of the final compounds was adequately confirmed on the basis of FT-IR and 1H NMR as well as elemental analyses.

  6. Anticancer Effects of Salvia miltiorrhiza Alcohol Extract on Oral Squamous Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Wen-Hung Wang

    2017-01-01

    Full Text Available Researchers have reported significant effects from Danshen (Salvia miltiorrhiza in terms of inhibiting tumor cell proliferation and promoting apoptosis in breast cancer, hepatocellular carcinomas, promyelocytic leukemia, and clear cell ovary carcinomas. Here we report our data indicating that Danshen extracts, especially alcohol extract, significantly inhibited the proliferation of the human oral squamous carcinoma (OSCC cell lines HSC-3 and OC-2. We also observed that Danshen alcohol extract activated the caspase-3 apoptosis executor by impeding members of the inhibitor of apoptosis (IAP family, but not by regulating the Bcl-2-triggered mitochondrial pathway in OSCC cells. Our data also indicate that the extract exerted promising effects in vivo, with HSC-3 tumor xenograft growth being suppressed by 40% and 69% following treatment with Danshen alcohol extract at 50 and 100 mg/kg, respectively, for 34 days. Combined, our results indicate appreciable anticancer activity and significant potential for Danshen alcohol extract as a natural antioxidant and herbal human oral cancer chemopreventive drug.

  7. Analysis of antifungal and anticancer effects of the extract from Pelargonium zonale.

    Science.gov (United States)

    Lewtak, Kinga; Fiołka, Marta J; Szczuka, Ewa; Ptaszyńska, Aneta A; Kotowicz, Natalia; Kołodziej, Przemysław; Rzymowska, Jolanta

    2014-11-01

    The extract from Pelargonium zonale stalks exhibits activity against Candida albicans and exerts an effect on the HeLa cell line. The action against C. albicans cells was analysed using light, CLSM, SEM, and TEM microscopes. The observations indicate that the extract influenced fungal cell morphology and cell metabolic activity. The morphological changes include cell wall damage, deformations of cell surfaces, and abnormalities in fungal cell shape and size. Cells of C. albicans treated with the extract exhibited disturbances in the budding pattern and a tendency to form agglomerates and multicellular chains. The P. zonale extract caused a significant decrease in the metabolic activity of C. albicans cells. Cells died via both apoptosis and necrosis. The antitumor activity of the extract was analysed using the MTT assay. The P. zonale extract exhibited minor cytotoxicity against the HeLa cell line but a dose-dependent cytopathic effect was noticed. The P. zonale extract is a promising source for the isolation of antifungal and anticancer compounds.

  8. Synergistic Anticancer Effect of Tocotrienol Combined with Chemotherapeutic Agents or Dietary Components: A Review

    Directory of Open Access Journals (Sweden)

    Takahiro Eitsuka

    2016-09-01

    Full Text Available Tocotrienol (T3, unsaturated vitamin E, is gaining a lot of attention owing to its potent anticancer effect, since its efficacy is much greater than that of tocopherol (Toc. Various factors are known to be involved in such antitumor action, including cell cycle arrest, apoptosis induction, antiangiogenesis, anti-metastasis, nuclear factor-κB suppression, and telomerase inhibition. Owing to a difference in the affinity of T3 and Toc for the α-tocopherol transfer protein, the bioavailability of orally ingested T3 is lower than that of Toc. Furthermore, cellular uptake of T3 is interrupted by coadministration of α-Toc in vitro and in vivo. Based on this, several studies are in progress to screen for molecules that can synergize with T3 in order to augment its potency. Combinations of T3 with chemotherapeutic drugs (e.g., statins, celecoxib, and gefitinib or dietary components (e.g., polyphenols, sesamin, and ferulic acid exhibit synergistic actions on cancer cell growth and signaling pathways. In this review, we summarize the current status of synergistic effects of T3 and an array of agents on cancer cells, and discuss their molecular mechanisms of action. These combination strategies would encourage further investigation and application in cancer prevention and therapy.

  9. Synergistic Anticancer Effect of Tocotrienol Combined with Chemotherapeutic Agents or Dietary Components: A Review

    Science.gov (United States)

    Eitsuka, Takahiro; Tatewaki, Naoto; Nishida, Hiroshi; Nakagawa, Kiyotaka; Miyazawa, Teruo

    2016-01-01

    Tocotrienol (T3), unsaturated vitamin E, is gaining a lot of attention owing to its potent anticancer effect, since its efficacy is much greater than that of tocopherol (Toc). Various factors are known to be involved in such antitumor action, including cell cycle arrest, apoptosis induction, antiangiogenesis, anti-metastasis, nuclear factor-κB suppression, and telomerase inhibition. Owing to a difference in the affinity of T3 and Toc for the α-tocopherol transfer protein, the bioavailability of orally ingested T3 is lower than that of Toc. Furthermore, cellular uptake of T3 is interrupted by coadministration of α-Toc in vitro and in vivo. Based on this, several studies are in progress to screen for molecules that can synergize with T3 in order to augment its potency. Combinations of T3 with chemotherapeutic drugs (e.g., statins, celecoxib, and gefitinib) or dietary components (e.g., polyphenols, sesamin, and ferulic acid) exhibit synergistic actions on cancer cell growth and signaling pathways. In this review, we summarize the current status of synergistic effects of T3 and an array of agents on cancer cells, and discuss their molecular mechanisms of action. These combination strategies would encourage further investigation and application in cancer prevention and therapy. PMID:27669218

  10. Anti-cancer effect of Cordyceps militaris in human colorectal carcinoma RKO cells via cell cycle arrest and mitochondrial apoptosis

    OpenAIRE

    Lee, Hwan Hee; Lee, Seulki; Lee, Kanghyo; Shin, Yu Su; Kang, Hyojeung; Cho, Hyosun

    2015-01-01

    Background Cordyceps militaris has been used as a traditional medicine in Asian countries for a long time. Different types of Cordyceps extract were reported to have various pharmacological activities including an anti-cancer effect. We investigated the inhibitory effect of Cordyceps militaris ethanol extract on a human colorectal cancer-derived cell line, RKO. Methods RKO cells were treated with various concentrations of nucleosides-enriched ethanol extract of Cordyceps militaris for 48 h an...

  11. Inhibition of autophagic flux by salinomycin results in anti-cancer effect in hepatocellular carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Johannes Klose

    Full Text Available Salinomycin raised hope to be effective in anti-cancer therapies due to its capability to overcome apoptosis-resistance in several types of cancer cells. Recently, its effectiveness against human hepatocellular carcinoma (HCC cells both in vitro and in vivo was demonstrated. However, the mechanism of action remained unclear. Latest studies implicated interference with the degradation pathway of autophagy. This study aimed to determine the impact of Salinomycin on HCC-autophagy and whether primary human hepatocytes (PHH likewise are affected. Following exposure of HCC cell lines HepG2 and Huh7 to varying concentrations of Salinomycin (0-10 µM, comprehensive analysis of autophagic activity using western-blotting and flow-cytometry was performed. Drug effects were analyzed in the settings of autophagy stimulation by starvation or PP242-treatment and correlated with cell viability, proliferation, apoptosis induction, mitochondrial mass accumulation and reactive oxygen species (ROS formation. Impact on apoptosis induction and cell function of PHH was analyzed. Constitutive and stimulated autophagic activities both were effectively suppressed in HCC by Salinomycin. This inhibition was associated with dysfunctional mitochondria accumulation, increased apoptosis and decreased proliferation and cell viability. Effects of Salinomycin were dose and time dependent and could readily be replicated by pharmacological and genetic inhibition of HCC-autophagy alone. Salinomycin exposure to PHH resulted in transient impairment of synthesis function and cell viability without apoptosis induction. In conclusion, our data suggest that Salinomycin suppresses late stages of HCC-autophagy, leading to impaired recycling and accumulation of dysfunctional mitochondria with increased ROS-production all of which are associated with induction of apoptosis.

  12. Inhibition of autophagic flux by salinomycin results in anti-cancer effect in hepatocellular carcinoma cells.

    Science.gov (United States)

    Klose, Johannes; Stankov, Metodi V; Kleine, Moritz; Ramackers, Wolf; Panayotova-Dimitrova, Diana; Jäger, Mark D; Klempnauer, Jürgen; Winkler, Michael; Bektas, Hüseyin; Behrens, Georg M N; Vondran, Florian W R

    2014-01-01

    Salinomycin raised hope to be effective in anti-cancer therapies due to its capability to overcome apoptosis-resistance in several types of cancer cells. Recently, its effectiveness against human hepatocellular carcinoma (HCC) cells both in vitro and in vivo was demonstrated. However, the mechanism of action remained unclear. Latest studies implicated interference with the degradation pathway of autophagy. This study aimed to determine the impact of Salinomycin on HCC-autophagy and whether primary human hepatocytes (PHH) likewise are affected. Following exposure of HCC cell lines HepG2 and Huh7 to varying concentrations of Salinomycin (0-10 µM), comprehensive analysis of autophagic activity using western-blotting and flow-cytometry was performed. Drug effects were analyzed in the settings of autophagy stimulation by starvation or PP242-treatment and correlated with cell viability, proliferation, apoptosis induction, mitochondrial mass accumulation and reactive oxygen species (ROS) formation. Impact on apoptosis induction and cell function of PHH was analyzed. Constitutive and stimulated autophagic activities both were effectively suppressed in HCC by Salinomycin. This inhibition was associated with dysfunctional mitochondria accumulation, increased apoptosis and decreased proliferation and cell viability. Effects of Salinomycin were dose and time dependent and could readily be replicated by pharmacological and genetic inhibition of HCC-autophagy alone. Salinomycin exposure to PHH resulted in transient impairment of synthesis function and cell viability without apoptosis induction. In conclusion, our data suggest that Salinomycin suppresses late stages of HCC-autophagy, leading to impaired recycling and accumulation of dysfunctional mitochondria with increased ROS-production all of which are associated with induction of apoptosis.

  13. Structural characterization of a broccoli polysaccharide and evaluation of anti-cancer cell proliferation effects.

    Science.gov (United States)

    Xu, Lishan; Cao, Jingjing; Chen, Wenrong

    2015-08-01

    Broccoli is a widely consumed vegetable with abundant amount of nutrients, which bring numerous beneficial effects on human health. The structural information of water-soluble polysaccharides in broccoli was eludicated for the first time in this work. A purified polysaccharide fraction (BPCa) was obtained by column chromatography. It comprised of arabinose (Ara), galactose (Gal), rhamnose (Rha) with a molar ratio of 5.3:0.8:1.0. Nuclear magnetic resonnance spectra data revealed that α-L-1,5-Araf and α-L-1,3,5-Araf are present in the backbone, while α-L-Araf terminal was attended in side chain. α-L-1,2-Rhap was found to be linked to α-L-1,5-Araf in heteronuclear multiple bond correlation spectra. The presences of β-D-1,4-Galp and α-D-1,4-GalpA were also detected. Furthermore, BPCa showed significant anti-cancer cell proliferation activities against HepG2, Siha and MDA-MB-231 carcinoma cell lines. The results indicated that BPCa had a good potential to be applied as functional food additives.

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

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    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. 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.

  16. Training data selection method for prediction of anticancer drug effects using a genetic algorithm with local search.

    Science.gov (United States)

    Hiroyasu, Tomoyuki; Miyabe, Yota; Yokouchi, Hisatake

    2011-01-01

    Here, we propose a training data selection method using a Support Vector Machine (SVM) to predict the effects of anticancer drugs. Conventionally, SVM is used for distinguishing between several types of data. However, in the method proposed here, the SVM is used to distinguish areas with only one or two types of data. The proposed method treats training data selection as an optimization problem and involves application of a genetic algorithm (GA). Moreover, GA with local search was applied to find the solution as the target problem was difficult to find. The composition method of GA for proposed method was examined. To determine its effectiveness, the proposed method was applied to an artificial anticancer drug data set. The verification results showed that the proposed method can be used to create a verifiable and predictable discriminant function by training data selection.

  17. Furanodiene enhances the anti-cancer effects of doxorubicin on ERα-negative breast cancer cells in vitro.

    Science.gov (United States)

    Zhong, Zhang-Feng; Qiang, Wen-An; Wang, Chun-Ming; Tan, Wen; Wang, Yi-Tao

    2016-03-05

    Furanodiene is a natural product isolated from Rhizoma curcumae, and exhibits broad-spectrum anti-cancer activities in vitro and in vivo. Our previous study proved that furanodiene could increase growth inhibition of steroidal agent in ERα-positive breast cancer cells, but whether furanodiene can influence ER status is not clear. In this study, we confirmed that furanodiene down-regulated the ERα protein expression level and inhibited E2-induced estrogen response element (ERE)-driven reporter plasmid activity in ERα-positive MCF-7 cells. Actually, ERα-knockdown cells were more sensitive than ERα positive cells to furanodiene on the cytotoxicity effect. So the anti-cancer effects of furanodiene and non-steroidal agent in breast cancer cells still requires further investigation. Our results showed that furanodiene exposure could enhance growth inhibitory effects of doxorubicin in ERα-negative MDA-MB-231 cells and ERα-low expression 4T1 cells. However, furanodiene did not increase the cytotoxicity of doxorubicin in ERα-positive breast cancer cells, non-tumorigenic breast epithelial cells, macrophage cells, hepatocytes cells, pheochromocytoma cells and cardiac myoblasts cells. Furanodiene enhances the anti-cancer effects of doxorubicin in ERα-negative breast cancer cells through suppressing cell viability via inducing apoptosis in mitochondria-caspases-dependent and reactive oxygen species-independent manners. These results indicate that furanodiene may be a promising and safety natural agent for cancer adjuvant therapy in the future.

  18. The novel microtubule-interfering agent TZT-1027 enhances the anticancer effect of radiation in vitro and in vivo.

    Science.gov (United States)

    Akashi, Y; Okamoto, I; Suzuki, M; Tamura, K; Iwasa, T; Hisada, S; Satoh, T; Nakagawa, K; Ono, K; Fukuoka, M

    2007-05-21

    TZT-1027 is a novel anticancer agent that inhibits microtubule polymerisation and manifests potent antitumour activity in preclinical models. We have examined the effect of TZT-1027 on cell cycle progression as well as the anticancer activity of this drug both in vitro and in vivo. With the use of tsFT210 cells, which express a temperature-sensitive mutant of Cdc2, we found that TZT-1027 arrests cell cycle progression in mitosis, the phase of the cell cycle most sensitive to radiation. A clonogenic assay indeed revealed that TZT-1027 increased the sensitivity of H460 cells to gamma-radiation, with a dose enhancement factor of 1.2. Furthermore, TZT-1027 increased the radiosensitivity of H460 and A549 cells in nude mice, as revealed by a marked delay in tumour growth and an enhancement factor of 3.0 and 2.2, respectively. TZT-1027 also potentiated the induction of apoptosis in H460 cells by radiation both in vitro and in vivo. Histological evaluation of H460 tumours revealed that TZT-1027 induced morphological damage to the vascular endothelium followed by extensive central tumour necrosis. Our results thus suggest that TZT-1027 enhances the antitumour effect of ionising radiation, and that this action is attributable in part to potentiation of apoptosis induction and to an antivascular effect. Combined treatment with TZT-1027 and radiation therefore warrants investigation in clinical trials as a potential anticancer strategy.

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

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    Anna Boss

    2016-08-01

    Full Text Available 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.

  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

    2016-08-19

    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.

  2. Effects of culture medium compositions on antidiabetic activity and anticancer activity of marine endophitic bacteria isolated from sponge

    Science.gov (United States)

    Maryani, Faiza; Mulyani, Hani; Artanti, Nina; Udin, Linar Zalinar; Dewi, Rizna Triana; Hanafi, Muhammad; Murniasih, Tutik

    2017-01-01

    High diversity of Indonesia marine spesies and their ability in producing secondary metabolite that can be used as a drug candidate cause this fascinating topic need to explore. Most of marine organisms explored to discover drug is macroorganism whereas microorganism (such as Indonesia marine bacteria) is very limited. Therefore, in this report, antidiabetic and anticancer activity of Indonesia marine bacteria isolated from Sponges's extract have been studied. Bacteria strain 8.9 which are collection of Research Center for Oseanography, Indonesian Institute of Sciences were from Barrang Lompo Island, Makasar, Indonesia. Bacteria were cultured in different culture medium compositions (such as: different pH, source of glucose and water) for 48 hours on a shaker, then they were extracted with ethyl asetate. Extracts of bacteria were tested by DPPH method (antioxidant activity), alpha glucosidase inhibitory activity method (antidiabetic activity), and Alamar Blue assay (anticancer activity) at 200 ppm. According to result, extract of bacteria in pH 8.0 exhibited the greatest antioxidant (19.27% inhibition), antidiabetic (63.95% inhibition) and anticancer activity of T47D cell line (44.62% cell viability) compared to other extracts. However, effect of addition of sugar sources (such as: glucose, sucrose, and soluble starch) and effect of addition of water/sea water exhibited less influence on their bioactivities. In conclusion, Indonesia marine bacteria isolated from sponge have potential a source of bioactive compound in drug discovery field.

  3. Mechanisms mediating the synergistic anticancer effects of combined γ-tocotrienol and sesamin treatment.

    Science.gov (United States)

    Akl, Mohamed R; Ayoub, Nehad M; Sylvester, Paul W

    2012-11-01

    Epidemiological studies have highlighted the ability of phytochemicals to reduce the risk of breast cancer by attenuating specific intracellular signaling pathways that regulate cell proliferation and survival. γ-Tocotrienol is a natural form of vitamin E that displays potent anticancer activity at doses that have no discernible toxicity toward normal cells. Sesamin is an abundant phytochemical found in sesame seed oil that also shows antiproliferative and antiangiogenic activity against human breast cancer cells. In this study, the combined treatment of subeffective doses of γ-tocotrienol and sesamin caused a synergistic inhibition of murine +SA mammary epithelial cell growth, as determined by the MTT assay and immunofluorescent Ki-67 staining. Western blot studies revealed that combined low-dose treatment of γ-tocotrienol and sesamin caused a marked reduction in EGF-induced ErbB3 and ErbB4 receptors phosphorylation (activation) and a relatively large decrease in intracellular levels of total and/or phosphorylated c-Raf, MEK1/2, ERK1/2, PI3K, PDK1, Akt, p-NFκB, Jak1, Jak2, and Stat1, as compared to cells treated with only one compound or in the vehicle-treated control group. These findings demonstrate that the synergistic growth inhibitory effects of γ-tocotrienol and sesamin treatment are associated with suppression of EGF-dependent mitogenic signaling in mammary tumor cells and suggest that dietary supplementation with these phytochemicals may provide some benefits in the prevention and/or treatment of breast cancer.

  4. Potentiating effect of UVA irradiation on anticancer activity of Carboplatin derivatives involving 7-azaindoles.

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    Pavel Štarha

    Full Text Available The moderate-to-high in vitro cytotoxicity against ovarian A2780 (IC50 = 4.7-14.4 μM, prostate LNCaP (IC50 = 18.7-30.8 μM and prostate PC-3 (IC50 = 17.6-42.3 μM human cancer cell lines of the platinum(II cyclobutane-1,1'-dicarboxylato complexes [Pt(cbdc(naza2] (1-6; cbdc = cyclobutane-1,1'-dicarboxylate(2-; naza = halogeno-substituted 7-azaindoles, derived from the anticancer metallodrug carboplatin, are reported. The complexes containing the chloro- and bromo-substituted 7-azaindoles (1, 2, and 4-6 showed a significantly higher (p < 0.05 cytotoxicity against A2780 cell line as compared to cisplatin used as a reference drug. Addition of the non-toxic concentration (5.0 μM of L-buthionine sulfoximine (L-BSO, an effective inhibitor of γ-glutamylcysteine synthase markedly increases the in vitro cytotoxicity of the selected complex 3 against A2780 cancer cell line by a factor of about 4.4. The cytotoxicity against A2780 and LNCaP cells, as well as the DNA platination, were effectively enhanced by UVA light irradiation (λmax = 365 nm of the complexes, with the highest phototoxicity determined for compound 3, resulting in a 4-fold decline in the A2780 cells viability from 25.1% to 6.1%. The 1H NMR and ESI-MS experiments suggested that the complexes did not interact with glutathione as well as their ability to interact with guanosine monophosphate. The studies also confirmed UVA light induced the formation of the cis [Pt(H2O2(cbdc`(naza] intermediate, where cbdc` represents monodentate-coordinated cbdc ligand, which is thought to be responsible for the enhanced cytotoxicity. This is further supported by the results of transcription mapping experiments showing that the studied complexes preferentially form the bifunctional adducts with DNA under UVA irradiation, in contrast to the formation of the less effective monofunctional adducts in dark.

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

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    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.

  6. Anticancer effect and apoptosis induction of gambogic acid in human gastric cancer line BGC-823

    Institute of Scientific and Technical Information of China (English)

    Wei Liu; Qing-Long Guo; Qi-Dong You; Li Zhao; Hong-Yan Gu; Sheng-Tao Yuan

    2005-01-01

    AIM: To investigate the anticancer effect of a traditional Chinese medicine gambogic acid (GA) in human gastric cancer line BGC-823 and further study the mechanism of apoptosis induction of GA.METHODS: Low differential human gastric cancer line BGC-823 were treated with GA at different doses and different times, the inhibitory rates were detected by MTT assay. Apoptosis induced by GA in BGC-823 cells was observed by Annexin-V/PI doubling staining flow cytometry assay. And T/C (%) was chosen to detect the inhibition of GA on human gastric adenocarcinoma BGC-823 nude mice xenografts. Apoptosis on nude mice xenografts was observed by Annexin-V/PI doubling staining flow cytometry assay and DNA fragmentation assay. To further determine the molecular mechanism of apoptosis induced by GA, the changes on the expression of bcl-2 and bax genes were detected by RT-PCR.RESULTS: After incubation with GA, low differential human gastric cancer line BGC-823 was dramatically inhibited in a dose-dependent manner. After these cells were exposedto GA for 24, 48 and 72 h, the IC50 value was 1.02±0.05, 1.41±0.20 and 1.14±0.19 μmol/L, respectively. Apoptosis in BGC-823 cells induced by GA was observed by AnnexinV/PI doubling staining flow cytometry assay. The apoptotic population of BGC-823 cells was about 12.96% and 24.58%, respectively, when cells were incubated with 1.2 μmol/L GA for 48 and 72 h. T/C (%) of human gastric carcinoma adenocarcinoma BGC-823 nude mice xenografts was 44.3, when the nude mice were treated with GA (8 mg/kg). Meanwhile, apoptosis induced by GA was observed in human gastric carcinoma adenocarcinoma BGC-823 nude mice xenografts. The increase of bax gene and the decrease of bc1-2 gene expressions were found by RT-PCR.CONCLUSION: The inhibition of GA on human gastric cancer line BGC-823 was confirmed. This effect connects with the inducing apoptosis in BGC-823 cells and the molecular mechanism might be related to the reduction of expression of apoptosis

  7. 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.

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

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

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    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

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

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    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

  11. Anticancer Effects of the Marine Sponge Lipastrotethya sp. Extract on Wild-Type and p53 Knockout HCT116 Cells

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    Kiheon Choi

    2017-01-01

    Full Text Available Interest in marine bioresources is increasing in the drug development sector. In particular, marine sponges produce a wide range of unique metabolites that enable them to survive in challenging environments, which makes them attractive sources of candidate pharmaceuticals. In previous study, we investigated over 40 marine specimens collected in Micronesia and provided by the Korean Institute of Ocean Science and Technology, for their antiproliferative effects on various cancer cell lines, and Lipastrotethya sp. extract (LSSE was found to have a marked antiproliferative effect. In the present study, we investigated the mechanism responsible for its anticancer effect on wild-type p53 (WT or p53 knockout (KO HCT116 cells. LSSE inhibited cell viability and induced apoptotic cell death more so in HCT116 p53 KO cells than the WT. HCT116 WT cells treated with LSSE underwent apoptosis associated with the induction of p53 and its target genes. On the other hand, in HCT116 p53 KO cells, LSSE reduced mTOR and Bcl-2 and increased Beclin-1 and LC3-II protein levels, suggesting autophagy induction. These results indicate that the mechanisms responsible for the anticancer effect of LSSE depend on p53 status.

  12. Effect of Tea Polyphenol Compounds on Anticancer Drugs in Terms of Anti-Tumor Activity, Toxicology, and Pharmacokinetics

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    Jianhua Cao

    2016-12-01

    Full Text Available Multidrug resistance and various adverse side effects have long been major problems in cancer chemotherapy. Recently, chemotherapy has gradually transitioned from mono-substance therapy to multidrug therapy. As a result, the drug cocktail strategy has gained more recognition and wider use. It is believed that properly-formulated drug combinations have greater therapeutic efficacy than single drugs. Tea is a popular beverage consumed by cancer patients and the general public for its perceived health benefits. The major bioactive molecules in green tea are catechins, a class of flavanols. The combination of green tea extract or green tea catechins and anticancer compounds has been paid more attention in cancer treatment. Previous studies demonstrated that the combination of chemotherapeutic drugs and green tea extract or tea polyphenols could synergistically enhance treatment efficacy and reduce the adverse side effects of anticancer drugs in cancer patients. In this review, we summarize the experimental evidence regarding the effects of green tea-derived polyphenols in conjunction with chemotherapeutic drugs on anti-tumor activity, toxicology, and pharmacokinetics. We believe that the combination of multidrug cancer treatment with green tea catechins may improve treatment efficacy and diminish negative side effects.

  13. 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

  14. Cyclosporin A Decreases Human Macrophage Interleukin-6 Synthesis at Post-Transcriptional Level

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    Juan E. Losa García

    1999-01-01

    Full Text Available In addition to its well-established effect on T cells, cyclosporin A (CsA also inhibits inflammatory cytokine production by macrophages. However, little is known about the mechanism of action of CsA on macrophage cytokine production. We measured the effect of CsA on basal and phorbol-myristate-acetate (PMA-stimulated production of interleukin-6 using the human monocyte cell line U937 differentiated with dimethylsulfoxide (DMSO. Interleukin-6 levels were measured in supernatant and cell lysates using specific enzyme-linked immunosorbent assays. We found that CsA decreases not only IL-6 release but also cytokine synthesis. The concentration of CsA used did not affect either cell viability or proliferation. Three possibilities may be advanced to explain the CsA-due decrease in IL-6 production by macrophages: (a inhibition of the synthesis of an early common regulatory protein, (b inhibition of cytokine gene transcription, or (c modulation of post-transcriptional events. The first possibility was tested by measuring the effect of cycloheximide on the experimental system during the first 3 hours of culture. Although cycloheximide decreased total cytokine synthesis, the pattern of cytokine modulation by CsA persisted. These data suggest that CsA-mediated macrophage cytokine inhibition is not mediated by an early common regulatory protein. To further explore the inhibition mechanism, we measured IL-6 mRNA levels by Northern blot. IL-6 mRNA levels were unaffected by CsA both in resting and PMA-stimulated cells. We conclude that in human macrophages CsA diminishes IL-6 production at post-transcriptional level.

  15. Anticancer effects on leiomyosarcoma-bearing Wistar rats after electromagnetic radiation of resonant radiofrequencies.

    Science.gov (United States)

    Avdikos, Antonios; Karkabounas, Spyridon; Metsios, Apostolos; Kostoula, Olga; Havelas, Konstantinos; Binolis, Jayne; Verginadis, Ioannis; Hatziaivazis, George; Simos, Ioannis; Evangelou, Angelos

    2007-01-01

    number of tumors were completely regretted (final tumor induction: 66%). Both Groups of animals inoculated with exposed or non-exposed to the EMF LSC, (EG-I and EG-II, respectively) demonstrated a significant prolongation of the survival time and a lower tumor growth rate, in comparison to the control Group (CG) and the experimental control Group (ECG). However, the survival time of EG-I animals was found to be significantly longer and tumor growth rate significantly lower compared to EG-II animals. In conclusion, our results indicate a specific anticancer effect of resonant EMF irradiation. These results may possibly be attributed to (a) the duration of exposure of LSC and (b) the exposure of the entire animal to this irradiation.

  16. Orthogonally functionalized nanoscale micelles for active targeted codelivery of methotrexate and mitomycin C with synergistic anticancer effect.

    Science.gov (United States)

    Li, Yang; Lin, Jinyan; Wu, Hongjie; Chang, Ying; Yuan, Conghui; Liu, Cheng; Wang, Shuang; Hou, Zhenqing; Dai, Lizong

    2015-03-02

    The design of nanoscale drug delivery systems for the targeted codelivery of multiple therapeutic drugs still remains a formidable challenge (ACS Nano, 2013, 7, 9558-9570; ACS Nano, 2013, 7, 9518-9525). In this article, both mitomycin C (MMC) and methotrexate (MTX) loaded DSPE-PEG micelles (MTX-M-MMC) were prepared by self-assembly using the dialysis technique, in which MMC-soybean phosphatidylcholine complex (drug-phospholipid complex) was encapsulated within MTX-functionalized DSPE-PEG micelles. MTX-M-MMC could coordinate an early phase active targeting effect with a late-phase synergistic anticancer effect and enable a multiple-responsive controlled release of both drugs (MMC was released in a pH-dependent pattern, while MTX was released in a protease-dependent pattern). Furthermore, MTX-M-MMC could codeliver both drugs to significantly enhance the cellular uptake, intracellular delivery, cytotoxicity, and apoptosis in vitro and improve the tumor accumulation and penetration and anticancer effect in vivo compared with either both free drugs treatment or individual free drug treatment. To our knowledge, this work provided the first example of the systemically administrated, orthogonally functionalized, and self-assisted nanoscale micelles for targeted combination cancer chemotherapy. The highly convergent therapeutic strategy opened the door to more simplified, efficient, and flexible nanoscale drug delivery systems.

  17. Anticancer Effects of Fusion Protein CAtin on DMBA-induced Carcinogenesis in Buccal Pouch of Chinese Hamster

    Institute of Scientific and Technical Information of China (English)

    BAI Jie-ying; LI Xiao; LI Chang; ZHANG Xiao-fei; LI Zhi-xin; ZHAO Shuang; LIU Xiao; ZENG Lin; CHI Bao-rong

    2012-01-01

    Aberrant expression ofcarcinoembryonic antigen(CEA)is a common feature for multiple types of cancer,which makes it an attractive target for anticancer therapy.CAtin is a novel dual cancer-specific fusion protein,composed of an anti-CEA single-chain disulfide-stabilized Fv antibody(scdsFv)and Apoptin,a tumor-specific apoptosis-inducing protein.Oral squamous cell carcinoma(OSCC)is an important healthcare problem in the clinic.To evaluate the anticancer effects of CAtin on OSCC,7,12-dimethylbenz[a]anthracene(DMBA)was used to induce oral carcinogenesis and premalignant lesions in the buccal pouch of Chinese hamster,and the antitumor effects of CAtin were determined in pre-cancer,cancer and post-operatative cancer models,respectively.The results show that the administration of CAtin delayed the malignant transformation of early stage cancerous lesions,inhibited the growth of established solid oral tumors and reduced the post-operatative relapse of lesions,with no significant systemic toxicity.This study demonstrates that CAtin may have potential for the treatment of OSCC,and the development of preventive strategies based on CAtin may offer a practical approach for the treatment of human oral tumors.

  18. PEG-PE micelles loaded with paclitaxel and surface-modified by a PBR-ligand: synergistic anticancer effect

    Science.gov (United States)

    Musacchio, Tiziana; Laquintana, Valentino; Latrofa, Andrea; Trapani, Giuseppe; Torchilin, Vladimir P.

    2009-01-01

    Selective ligands to the Peripheral Benzodiazepine Receptor (PBR) may induce apoptosis and cell cycle arrest. An over-expression of PBR in certain cancers allowed us to consider the use of highly selective ligands to PBR for receptor-mediated drug targeting to tumors. With this in mind, we prepared PBR-targeted nanoparticulate drug delivery systems (PEG-PE micelles) loaded with the anticancer drug paclitaxel (PCL) to test possible synergistic anticancer effects. PEG2k-PE-based polymeric micelles with and without PCL were prepared in HBS, pH 7.5, and conjugated with a PBR-ligand (CB86) in 0.45% of DMSO. The cytotoxic effect of such micelles against the LN 18 human glioblastoma cell line was studied in cell culture. The micelles maintained their size and size distribution and remained intact without drug release after the PBR-ligand conjugation. The PCL-loaded PBR-targeted micelles showed a significantly enhanced toxicity against human glioblastoma LN 18 cancer cells in vitro. Thus, PBR-targeted nanopreparations may potentially serve as a new nanomedicine for targeted cancer therapy. PMID:19718800

  19. Anticancer effect and enhanced chemotherapy potential of resveratrol in human pancreatic cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    Sumei Chen; Guangsu Xiong; Ke Zhang; Co-first author Yuanyuan Chen; Ruzhen Zheng; Penjun Zhao; Jianwei Zhu; Shuming Wu; Qinghua Deng; Shenglin Ma

    2016-01-01

    Objective Gemcitabine, the only approved drug for the treatment of pancreatic cancer, is not very ef ec-tive. Novel and ef ective cancer chemopreventive agents are urgently needed. Recently, emerging studies determined resveratrol possessed anticancer ef ects on various cancer cel s. We explored the anticancer ef ect of resveratrol in pancreatic cancer cel s and investigated the involved moleculars of action. We also examined whether resveratrol enhanced antitumor activity of gemcitabine in vitro. Methods Proliferation inhibition was assessed by cel count kit-8 assay. Cel cycle phase distribution and apoptotic cel s were measured by flow cytometric analysis. We determined the expression of bcl-2, cyclinD1, and activation of caspases-3 and poly (ADP-ribose) polymerase1 proteins used Western blot analysis. Results Resveratrol inhibited the proliferation of three pancreatic cancer cel lines in a dose dependent fashion, and induced accumulation of cel s at the G1 phase as wel as apoptosis. Our data also demon-strated that resveratrol enhanced gemcitabine-induced apoptosis in pancreatic cancer cel s. In addition, resveratrol inhibited the expression of cyclinD1, bcl-2, and induced activation of caspase-3 and poly (ADP-ribose) polymerase1. Conclusion Our results suggested that resveratrol might be not only a potential regimen, but also an ef ective chemosensitizer for the chemotherapy of pancreatic cancer.

  20. POTENTIAL APPLICATIONS OF SOS-GFP BIOSENSOR TO IN VITRO RAPID SCREENING OF CYTOTOXIC AND GENOTOXIC EFFECT OF ANTICANCER AND ANTIDIABETIC PHARMACIST RESIDUES IN SURFACE WATER

    Directory of Open Access Journals (Sweden)

    Marzena Matejczyk

    2014-12-01

    Full Text Available Escherichia coli K-12 GFP-based bacterial biosensors allowed the detection of cytotoxic and genotoxic effect of anticancer drug– cyclophosphamide and antidiabetic drug – metformin in PBS buffer and surface water. Experimental data indicated that recA::gfpmut2 genetic system was sensitive to drugs and drugs mixture applied in experiment. RecA promoter was a good bioindicator in cytotoxic and genotoxic effect screening of cyclophosphamide, metformin and the mixture of the both drugs in PBS buffer and surface water. The results indicated that E. coli K-12 recA::gfp mut2 strain could be potentially useful for first-step screening of cytotoxic and genotoxic effect of anticancer and antidiabetic pharmacist residues in water. Next steps in research will include more experimental analysis to validate recA::gfpmut2 genetic system in E. coli K-12 on different anticancer drugs.

  1. Green tea polyphenols block the anticancer effects of bortezomib and other boronic acid-based proteasome inhibitors.

    Science.gov (United States)

    Golden, Encouse B; Lam, Philip Y; Kardosh, Adel; Gaffney, Kevin J; Cadenas, Enrique; Louie, Stan G; Petasis, Nicos A; Chen, Thomas C; Schönthal, Axel H

    2009-06-04

    The anticancer potency of green tea and its individual components is being intensely investigated, and some cancer patients already self-medicate with this "miracle herb" in hopes of augmenting the anticancer outcome of their chemotherapy. Bortezomib (BZM) is a proteasome inhibitor in clinical use for multiple myeloma. Here, we investigated whether the combination of these compounds would yield increased antitumor efficacy in multiple myeloma and glioblastoma cell lines in vitro and in vivo. Unexpectedly, we discovered that various green tea constituents, in particular (-)-epigallocatechin gallate (EGCG) and other polyphenols with 1,2-benzenediol moieties, effectively prevented tumor cell death induced by BZM in vitro and in vivo. This pronounced antagonistic function of EGCG was evident only with boronic acid-based proteasome inhibitors (BZM, MG-262, PS-IX), but not with several non-boronic acid proteasome inhibitors (MG-132, PS-I, nelfinavir). EGCG directly reacted with BZM and blocked its proteasome inhibitory function; as a consequence, BZM could not trigger endoplasmic reticulum stress or caspase-7 activation, and did not induce tumor cell death. Taken together, our results indicate that green tea polyphenols may have the potential to negate the therapeutic efficacy of BZM and suggest that consumption of green tea products may be contraindicated during cancer therapy with BZM.

  2. Targeted anti-cancer prodrug based on carbon nanotube with photodynamic therapeutic effect and pH-triggered drug release

    Energy Technology Data Exchange (ETDEWEB)

    Fan, Jianquan; Zeng, Fang, E-mail: mcfzeng@scut.edu.cn; Xu, Jiangsheng; Wu, Shuizhu, E-mail: shzhwu@scut.edu.cn [South China University of Technology, College of Materials Science and Engineering, State Key Laboratory of Luminescent Materials and Devices (China)

    2013-09-15

    Herein, we describe a multifunctional anti-cancer prodrug system based on water-dispersible carbon nanotube (CNT); this prodrug system features active targeting, pH-triggered drug release, and photodynamic therapeutic properties. For this prodrug system (with the size of {approx}100-300 nm), an anti-cancer drug, doxorubicin (DOX), was incorporated onto CNT via a cleavable hydrazone bond; and a targeting ligand (folic acid) was also coupled onto CNT. This prodrug can preferably enter folate receptor (FR)-positive cancer cells and undergo intracellular release of the drug triggered by the reduced pH. The targeted CNT-based prodrug system can cause lower cell viability toward FR-positive cells compared to the non-targeted ones. Moreover, the CNT carrier exhibits photodynamic therapeutic (PDT) action; and the cell viability of FR-positive cancer cells can be further reduced upon light irradiation. The dual effects of pH-triggered drug release and PDT increase the therapeutic efficacy of the DOX-CNT prodrug. This study may offer some useful insights on designing and improving the applicability of CNT for other drug delivery systems.

  3. Effect of Yiqi Jianpi plus anticancer herbs on spleen deficiency in colorectal cancer and its anti-tumor role

    Institute of Scientific and Technical Information of China (English)

    Li-Ran Fu; Sheng-Wei Guo; Xian-Hui Liu

    2014-01-01

    Objective:To observe the effect ofYiqiJianpi plus anticancer herbs on spleen deficiency in colorectal cancer and its anti-tumor role.Methods:Human intestinal cancer cellHT29 xenograft of nude mice model was established.The expression ofEGF,VEGF, gastric cancer tumor growth in mice were observed.Results:Protein kinaseC expression in in theYiqiJianpi group andYiqi Jianpi anti-tumor group was significantly better than the model group(P<0.01,P<0.05).There was significantly more apoptotic cells inYiqiJianpi anti-tumor group thanYiqiJianpi group and model group(P<0.01).Epidermal growth factor and vascular endothelial growth factor expression inYiqiJianpi group was significantly lower thanYiqiJianpi group and model group(P<0.05). Conclusions:Tumor can inhibit the expression ofPKC inhibition.YiqiJianpi and anticancer treatment can reduce this inhibition.Besides this treatment can also inhibit expression of tumor related genes such as epidermal growth factor and vascular endothelial growth factor.

  4. 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.

  5. Saponins from Chinese Medicines as Anticancer Agents

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    Xiao-Huang Xu

    2016-10-01

    Full Text Available Saponins are glycosides with triterpenoid or spirostane aglycones that demonstrate various pharmacological effects against mammalian diseases. To promote the research and development of anticancer agents from saponins, this review focuses on the anticancer properties of several typical naturally derived triterpenoid saponins (ginsenosides and saikosaponins and steroid saponins (dioscin, polyphyllin, and timosaponin isolated from Chinese medicines. These saponins exhibit in vitro and in vivo anticancer effects, such as anti-proliferation, anti-metastasis, anti-angiogenesis, anti-multidrug resistance, and autophagy regulation actions. In addition, related signaling pathways and target proteins involved in the anticancer effects of saponins are also summarized in this work.

  6. 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.

  7. Insights into the in vitro Anticancer Effects of Diruthenium-1.

    Science.gov (United States)

    Koceva-Chyła, Aneta; Matczak, Karolina; Hikisz, Msc Paweł; Durka, Msc Kamil; Kochel, Msc Krzysztof; Süss-Fink, Georg; Furrer, Julien; Kowalski, Konrad

    2016-10-06

    The in vitro anticancer activity of the dinuclear trithiolato-bridged arene ruthenium complex diruthenium-1 (DiRu-1) was evaluated against a panel of human cancer cell lines used as in vitro models for hepatocellular carcinoma (HepG2 cells), estrogen-responsive breast adenocarcinoma (MCF-7 cells), and triple-negative breast adenocarcinoma (MDA-MB-231 cells). DiRu-1 is highly cytotoxic to these cell lines, demonstrating half-maximal inhibitory concentrations (IC50 ) in the low-nanomolar range (77±1.4 to 268.2±4.4 nm). The main molecular mechanisms responsible for the high cytotoxicity of DiRu-1 against the most responsive MCF-7 cell line (IC50 =77±1.4 nm) were investigated on the basis of the capacity of DiRu-1 to induce oxidative stress, apoptosis, and DNA damage, and to inhibit the cell cycle and proliferation. The results show that DiRu-1 triggers caspase-dependent apoptosis in MCF-7 cells on both the intrinsic and extrinsic pathways. Moreover, the Ru complex also causes necrosis, mitotic catastrophe, and autophagy. DiRu-1 increases the intracellular levels of reactive oxygen species (ROS), which play a significant role in its cytotoxicity and pro-apoptotic activity. An important mechanism of the anticancer activity of DiRu-1 appears to be the induction of DNA lesions, mainly due to apoptotic DNA fragmentation and cell-cycle arrest at the G2 /M checkpoint. These changes are correlated with the concentration of DiRu-1, the duration of the cell treatment, and the post-treatment time.

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

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    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.

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

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    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

  10. Inflammation response at the transcriptional level of HepG2 cells induced by multi-walled carbon nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Piret, Jean-Pascal; Vankoningsloo, Sebastien; Noel, Florence; Saout, Christelle; Toussaint, Olivier [Research Unit in Cellular Biology (URBC), Narilis, University of Namur, 5000 Namur (Belgium); Mendoza, Jorge Mejia; Lucas, Stephane, E-mail: olivier.toussaint@fundp.ac.be [Research Center for the Physics of Matter and Radiation (PMR), Narilis, University of Namur, 5000 Namur (Belgium)

    2011-07-06

    Poor information are currently available about the biological effects of multi-walled carbon nanotubes (MWCNT) on the liver. In this study, we evaluated the effects of MWCNT at the transcriptional level on the classical in vitro model of HepG2 hepatocarcinoma cells. The expression levels of 96 transcript species implicated in the inflammatory and immune responses was studied after a 24h incubation of HepG2 cells in presence of raw MWCNT dispersed in water by stirring. Among the 46 transcript species detected, only a few transcripts including mRNA coding for interleukine-7, chemokines receptor of the C-C families CCR7, as well as Endothelin-1, were statistically more abundant after treatment with MWCNT. Altogether, these data indicate that MWCNT can only induce a weak inflammatory response in HepG2 cells.

  11. Inflammation response at the transcriptional level of HepG2 cells induced by multi-walled carbon nanotubes

    Science.gov (United States)

    Piret, Jean-Pascal; Vankoningsloo, Sébastien; Noël, Florence; Mejia Mendoza, Jorge; Lucas, Stéphane; Saout, Christelle; Toussaint, Olivier

    2011-07-01

    Poor information are currently available about the biological effects of multi-walled carbon nanotubes (MWCNT) on the liver. In this study, we evaluated the effects of MWCNT at the transcriptional level on the classical in vitro model of HepG2 hepatocarcinoma cells. The expression levels of 96 transcript species implicated in the inflammatory and immune responses was studied after a 24h incubation of HepG2 cells in presence of raw MWCNT dispersed in water by stirring. Among the 46 transcript species detected, only a few transcripts including mRNA coding for interleukine-7, chemokines receptor of the C-C families CCR7, as well as Endothelin-1, were statistically more abundant after treatment with MWCNT. Altogether, these data indicate that MWCNT can only induce a weak inflammatory response in HepG2 cells.

  12. Geranylated 4-Phenylcoumarins Exhibit Anticancer Effects against Human Prostate Cancer Cells through Caspase-Independent Mechanism.

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    Noor Shahirah Suparji

    Full Text Available Geranylated 4-phenylcoumarins, DMDP-1 & -2 isolated from Mesua elegans were investigated for anticancer potential against human prostate cancer cells. Treatment with DMDP-1 & -2 resulted in cell death in a time and dose dependent manner in an MTT assay on all cancer cell lines tested with the exception of lung adenocarcinoma cells. DMDP-1 showed highest cytotoxic efficacy in PC-3 cells while DMDP-2 was most potent in DU 145 cells. Flow cytometry indicated that both coumarins were successful to induce programmed cell death after 24 h treatment. Elucidation on the mode-of-action via protein arrays and western blotting demonstrated death induced without any significant expressions of caspases, Bcl-2 family proteins and cleaved PARP, thus suggesting the involvement of caspase-independent pathways. In identifying autophagy, analysis of GFP-LC3 showed increased punctate in PC-3 cells pre-treated with CQ and treated with DMDP-1. In these cells decreased expression of autophagosome protein, p62 and cathepsin B further confirmed autophagy. In contrary, the DU 145 cells pre-treated with CQ and treated with DMDP-2 has reduced GFP-LC3 punctate although the number of cells with obvious GFP-LC3 puncta was significantly increased in the inhibitor-treated cells. The increase level of p62 suggested leakage of cathepsin B into the cytosol to trigger potential downstream death mediators. This correlated with increased expression of cathepsin B and reduced expression after treatment with its inhibitor, CA074. Also auto-degradation of calpain-2 upon treatment with DMDP-1 &-2 and its inhibitor alone, calpeptin compared with the combination treatment, further confirmed involvement of calpain-2 in PC-3 and DU 145 cells. Treatment with DMDP-1 & -2 also showed up-regulation of total and phosphorylated p53 levels in a time dependent manner. Hence, DMDP-1 & -2 showed ability to activate multiple death pathways involving autophagy, lysosomal and endoplasmic reticulum death

  13. Anticancer effect of xanthohumol induces growth inhibition and apoptosis of human liver cancer through NF-κB/p53-apoptosis signaling pathway.

    Science.gov (United States)

    Zhao, Xiangqian; Jiang, Kai; Liang, Bin; Huang, Xiaoqiang

    2016-02-01

    Xanthohumol may prevent and cure diabetes and atherosis, have oxidation resistance and antiviral function as well as anticancer effect preventing cancer cell metastasis. We investigate whether the anticancer effect of xanthohumol induces growth inhibition and apoptosis of human liver cancer through NF-κB/p53-apoptosis signaling pathway. Human liver cancer HepG2 cell were treated with 10, 20, 30 and 40 µM xanthohumol for 48 h. The present study showed that the anticancer effect of xanthohumol was effective in inhibiting proliferation and inducing apoptosis of human liver cancer HepG2 cells. Furthermore, the caspase-3 activity of human liver cancer HepG2 cells was increased by xanthohumol. In addition, 48-h treatment with xanthohumol suppressed NF-κB expression and promoted p53, cleaved PARP, AIF and cytochrome c expression and downregulated XIAP and Bcl-2/Bax expression in human liver cancer HepG2 cells. Therefore, the anticancer effect of xanthohumol induces growth inhibition and apoptosis of human liver cancer through the NF-κB/p53-apoptosis signaling pathway.

  14. 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.

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

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    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.

  16. 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

  17. 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.

  18. Pharmacological levels of Withaferin A (Withania somnifera trigger clinically relevant anticancer effects specific to triple negative breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Katarzyna Szarc vel Szic

    Full Text Available Withaferin A (WA isolated from Withania somnifera (Ashwagandha has recently become an attractive phytochemical under investigation in various preclinical studies for treatment of different cancer types. In the present study, a comparative pathway-based transcriptome analysis was applied in epithelial-like MCF-7 and triple negative mesenchymal MDA-MB-231 breast cancer cells exposed to different concentrations of WA which can be detected systemically in in vivo experiments. Whereas WA treatment demonstrated attenuation of multiple cancer hallmarks, the withanolide analogue Withanone (WN did not exert any of the described effects at comparable concentrations. Pathway enrichment analysis revealed that WA targets specific cancer processes related to cell death, cell cycle and proliferation, which could be functionally validated by flow cytometry and real-time cell proliferation assays. WA also strongly decreased MDA-MB-231 invasion as determined by single-cell collagen invasion assay. This was further supported by decreased gene expression of extracellular matrix-degrading proteases (uPA, PLAT, ADAM8, cell adhesion molecules (integrins, laminins, pro-inflammatory mediators of the metastasis-promoting tumor microenvironment (TNFSF12, IL6, ANGPTL2, CSF1R and concomitant increased expression of the validated breast cancer metastasis suppressor gene (BRMS1. In line with the transcriptional changes, nanomolar concentrations of WA significantly decreased protein levels and corresponding activity of uPA in MDA-MB-231 cell supernatant, further supporting its anti-metastatic properties. Finally, hierarchical clustering analysis of 84 chromatin writer-reader-eraser enzymes revealed that WA treatment of invasive mesenchymal MDA-MB-231 cells reprogrammed their transcription levels more similarly towards the pattern observed in non-invasive MCF-7 cells. In conclusion, taking into account that sub-cytotoxic concentrations of WA target multiple metastatic effectors

  19. The anti-cancer effects of poi (Colocasia esculenta) on colonic adenocarcinoma cells In vitro.

    Science.gov (United States)

    Brown, Amy C; Reitzenstein, Jonathan E; Liu, Jessie; Jadus, Martin R

    2005-09-01

    Hawaiians tend to have lower incidence rates of colorectal cancer and it was hypothesized that this may be due to ethnic differences in diet, specifically, their consumption of poi, a starchy paste made from the taro (Colocasia esulenta L.) plant corm. Soluble extracts of poi were incubated at 100 mg/mL in vitro for antiproliferative activity against the rat YYT colon cancer cell line. (3)H-thymidine incorporation studies were conducted to demonstrate that the poi inhibited the proliferation of these cancer cells in a dose-dependent manner. The greatest suppression of YYT colon cancer growth occurred when 25% concentration was used. When poi was incubated with the YYT cells after 2 days, the YYT cells underwent apoptotic changes as evidenced by a positive terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) stain. Poi enhanced the proliferation of normal mouse splenocyte control cells, suggesting that poi is not simply toxic to all cells but even has a positive immunostimulatory role. By flow cytometry, T cells (CD4+ and CD8+) were predominantly activated by the poi. Although numerous factors can contribute to the risk of colon cancer, perhaps poi consumption may contribute to the lower colon cancer rates among Hawaiians by two distinct mechanisms. First, by inducing apoptosis within colon cancer cells; second, by non-specifically activating lymphocytes, which in turn can lyse cancerous cells. Our results suggest for the first time that poi may have novel tumor specific anti-cancer activities and future research is suggested with animal studies and human clinical trials.

  20. Regulation by gravity of the transcript levels of MAP65 in azuki bean epicotyls

    Science.gov (United States)

    Soga, Kouichi; Hoson, Takayuki; Wakabayashi, Kazuyuki; Kotake, Toshihisa

    2012-07-01

    Development of a short and thick body by reorientation of cortical microtubules is required for the resistance of plants to the gravitational force. The 65 kDa microtubule-associated protein (MAP65) has microtubule bundling activity and is involved in the reorientation of cortical microtubules. Here, we investigated the relation between the orientation of cortical microtubules and the transcript levels of VaMAP65-1 under centrifugal hypergravity conditions in azuki bean epicotyls. The percentage of cells with transverse microtubules was decreased, while that with longitudinal microtubules was increased, in proportion to the logarithm of the magnitude of gravity. The orientation of microtubules was restored to the original direction after removal of the hypergravity stimulus. The transcript level of VaMAP65-1 was down-regulated in proportion to the logarithm of the magnitude of gravity (R=-0.99). By removal of hypergravity stimulus, expression of VaMAP65-1 was increased to control levels. Strong correlations were observed between the percentage of cells with longitudinal or transverse microtubules and the transcript levels of VaMAP65-1 (R=-0.93, 0.91). These results suggest that down-regulation of VaMAP65-1 expression is involved in the regulation by gravity of the orientation of cortical microtubules in azuki bean epicotyls. Lanthanum and gadolinium ions, potential blockers of mechanosensitive calcium ion-permeable channels (mechanoreceptors), nullified the down-regulation of expression of VaMAP65-1 gene, suggesting that mechanoreceptors are responsible for regulation by gravity of VaMAP65-1 expression.

  1. Decreased Integrity, Content, and Increased Transcript Level of Mitochondrial DNA Are Associated with Keratoconus

    Science.gov (United States)

    Hao, Xiao-Dan; Chen, Zhao-Li; Qu, Ming-Li; Zhao, Xiao-Wen; Li, Su-Xia; Chen, Peng

    2016-01-01

    Oxidative stress may play an important role in the pathogenesis of keratoconus (KC). Mitochondrial DNA (mtDNA) is involved in mitochondrial function, and the mtDNA content, integrity, and transcript level may affect the generation of reactive oxygen species (ROS) and be involved in the pathogenesis of KC. We designed a case-control study to research the relationship between KC and mtDNA integrity, content and transcription. One-hundred ninety-eight KC corneas and 106 normal corneas from Chinese patients were studied. Quantitative real-time PCR was used to measure the relative mtDNA content, transcript levels of mtDNA and related genes. Long-extension PCR was used to detect mtDNA damage. ROS, mitochondrial membrane potential and ATP were measured by respective assay kit, and Mito-Tracker Green was used to label the mitochondria. The relative mtDNA content of KC corneas was significantly lower than that of normal corneas (P = 9.19×10−24), possibly due to decreased expression of the mitochondrial transcription factor A (TFAM) gene (P = 3.26×10−3). In contrast, the transcript levels of mtDNA genes were significantly increased in KC corneas compared with normal corneas (NADH dehydrogenase subunit 1 [ND1]: P = 1.79×10−3; cytochrome c oxidase subunit 1 [COX1]: P = 1.54×10−3; NADH dehydrogenase subunit 1, [ND6]: P = 4.62×10−3). The latter may be the result of increased expression levels of mtDNA transcription-related genes mitochondrial RNA polymerase (POLRMT) (P = 2.55×10−4) and transcription factor B2 mitochondrial (TFB2M) (P = 7.88×10−5). KC corneas also had increased mtDNA damage (P = 3.63×10−10), higher ROS levels, and lower mitochondrial membrane potential and ATP levels compared with normal corneas. Decreased integrity, content and increased transcript level of mtDNA are associated with KC. These changes may affect the generation of ROS and play a role in the pathogenesis of KC. PMID:27783701

  2. 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)

  3. Anti-cancer effects of blue-green alga Spirulina platensis, a natural source of bilirubin-like tetrapyrrolic compounds.

    Science.gov (United States)

    Koníčková, Renata; Vaňková, Kateřina; Vaníková, Jana; Váňová, Kateřina; Muchová, Lucie; Subhanová, Iva; Zadinová, Marie; Zelenka, Jaroslav; Dvořák, Aleš; Kolář, Michal; Strnad, Hynek; Rimpelová, Silvie; Ruml, Tomáš; J Wong, Ronald; Vítek, Libor

    2014-01-01

    Spirulina platensis is a blue-green alga used as a dietary supplement because of its hypocholesterolemic properties. Among other bioactive substances, it is also rich in tetrapyrrolic compounds closely related to bilirubin molecule, a potent antioxidant and anti-proliferative agent. The aim of our study was to evaluate possible anticancer effects of S. platensis and S. platensis-derived tetrapyrroles using an experimental model of pancreatic cancer. The anti-proliferative effects of S. platensis and its tetrapyrrolic components [phycocyanobilin (PCB) and chlorophyllin, a surrogate molecule for chlorophyll A] were tested on several human pancreatic cancer cell lines and xenotransplanted nude mice. The effects of experimental therapeutics on mitochondrial reactive oxygen species (ROS) production and glutathione redox status were also evaluated. Compared to untreated cells, experimental therapeutics significantly decreased proliferation of human pancreatic cancer cell lines in vitro in a dose-dependent manner (from 0.16 g•L-1 [S. platensis], 60 μM [PCB], and 125 μM [chlorophyllin], palga. Furthermore, it seems that dietary supplementation with this alga might enhance systemic pool of tetrapyrroles, known to be higher in subjects with Gilbert syndrome.

  4. Effects of natural nuclear factor-kappa B inhibitors on anticancer drug efflux transporter human P-glycoprotein.

    Science.gov (United States)

    Nabekura, Tomohiro; Hiroi, Takashi; Kawasaki, Tatsuya; Uwai, Yuichi

    2015-03-01

    Drug efflux transporter P-glycoprotein plays an important role in cancer chemotherapy. The nuclear factor-κB (NF-κB) transcription factors play critical roles in development and progression of cancer. In this study, the effects of natural compounds that can inhibit NF-κB activation on the function of P-glycoprotein were investigated using human MDR1 gene-transfected KB/MDR1 cells. The accumulation of daunorubicin or rhodamine 123, fluorescent substrates of P-glycoprotein, in KB/MDR1 cells increased in the presence of caffeic acid phenetyl ester (CAPE), licochalcone A, anacardic acid, celastrol, xanthohumol, magnolol, and honokiol in a concentration-dependent manner. In contrast, lupeol, zerumbone, thymoquinone, emodin, and anethol had no effects. The ATPase activities of P-glycoprotein were stimulated by CAPE, licochalcone A, anacardic acid, celastrol, xanthohumol, magnolol, and honokiol. Tumor necrosis factor (TNF)-α stimulated NF-κB activation was inhibited by CAPE, licochalcone A, anacardic acid, and xanthohumol. KB/MDR1 cells were sensitized to vinblastine cytotoxicity by CAPE, licochalcone A, anacardic acid, xanthohumol, magnolol, and honokiol, showing that these natural NF-κB inhibitors reverse multidrug resistance. These results suggest that natural compounds, such as CAPE, licochalcone A, and anacardic acid, have dual inhibitory effects on the anticancer drug efflux transporter P-glycoprotein and NF-κB activation, and may become useful to enhance the efficacy of cancer chemotherapy.

  5. Nutrition modulates Fto and Irx3 gene transcript levels, but does not alter their DNA methylation profiles in rat white adipose tissues.

    Science.gov (United States)

    Nowacka-Woszuk, Joanna; Pruszynska-Oszmalek, Ewa; Szydlowski, Maciej; Szczerbal, Izabela

    2017-02-05

    The fat mass and obesity associated (Fto) and iroquois homeobox 3 (Irx3) genes have been recognised as important obesity-related genes. Studies on the expression of these genes in the fat tissue of human and mouse have produced inconsistent results, while similar data on rat are limited. Environmental factors such as diet, should be considered as potential modulators of gene transcript levels through epigenetic mechanisms including DNA methylation. The aim of this study was to evaluate transcription levels and DNA methylation profiles of rat Fto and Irx3 genes in two white adipose tissue depots in response to high-fat and high-protein diets. The relative transcript levels of Fto and Irx3 were shown to be tissue-specific with higher levels detected in subcutaneous fat tissue than in abdominal fat tissue. Moreover, negative correlations between the transcripts of both genes were observed for subcutaneous fat tissue. The identified interactions (e.g. diet×duration of diet regimen) indicated that the diet had an impact on the transcript level; however, this effect was dependent on the duration of the diet regimen. The high-fat diet led to upregulation of Fto and Irx3 linearly with time across the two tissues. DNA methylation of the regulatory regions of the studied genes was very low and not related with the tissue, diet, or duration of diet regimen. Our study revealed that diet was an important factor modulating transcription of Fto and Irx3, but its affect depended on its duration. In contrast, the DNA methylation profiles of Fto and Irx3 were not altered by nutrition, which may indicate that the feeding type, when applied postnatally, did not affect DNA methylation of these genes.

  6. 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.

  7. Antimutagenic activity and in vitro anticancer effects of bamboo salt on HepG2 human hepatoma cells.

    Science.gov (United States)

    Zhao, Xin; Ju, Jaehyun; Kim, Hyung-Min; Park, Kun-Young

    2013-01-01

    Bamboo salt is a traditional Korean baked solar salt processed by packing the solar salt in bamboo joint cases and heating it several times to high temperatures. The antimutagenic activity and in vitro anticancer effects of bamboo salt on HepG2 human hepatoma cells were investigated and compared to those of other salt samples. Although solar salt and purified salt exhibited comutagenicity with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in the Salmonella typhimurium TA100 strain, bamboo salt was associated with a lower degree of comutagenicity or antimutagenic activity. Bamboo salt baked nine times (9×) showed a greater increase in antimutagenic activity than salts baked once (1×) or three times (3×). At a concentration of 1%, the growth rate of HepG2 cells treated with 9× bamboo salt determined by a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MIT) assay was reduced by 65%; this rate of inhibition was higher than that achieved with 1× baked bamboo salt (40%). Purified and solar salts had relatively lower inhibitory effects on growth rate (25% and 29%, respectively). Compared to the other salt samples, 9× bamboo salt significantly (pbamboo salts, especially 9× bamboo salt, also significantly (p<0.05) downregulated the expression of inflammation-related NF-κB, iNOS, and COX-2, and upregulated the gene expression of IκB-α compared to the other salt sample.

  8. RESEARCH PROGRESS ON ANTICANCER EFFECT OF TAUROLIDINE%Taurolidine抗肿瘤应用的研究进展

    Institute of Scientific and Technical Information of China (English)

    江涛; 于少卿; 薛学温

    2011-01-01

    Taurolidine is a broad-spectrum antibiotic and has been used to treat infectious diseases in clinics. In recent years, it is reported that Taurolidine has the anticancer activities.Although the mechanism has not completely known, the present research results show that Taurolidine's anti-tumor effects may be achieved by enhancing apoptosis, inhibiting angiogenesis and tumor adherence, down-regulating pro-inflammatory cytokine levels, and stimulating the immune system in response to surgically.%滔罗定(Taurolidine)是1种广谱抗菌药,临床上可用于多种感染疾病的治疗.近年来大量研究表明Taurolidine具有良好的抗肿瘤活性.Taurolidine的抗肿瘤机制尚未完全明确,已有的研究证明其通过促进细胞凋亡、抑制血管生成、减少肿瘤黏附、下调促炎细胞因子释放水平和刺激外科手术后抗肿瘤免疫调节等多种途径发挥抗肿瘤作用.本文综述Tauro1idine在抗肿瘤方面的研究进展.

  9. 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.

  10. Effect of Alstonia scholaris in enhancing the anticancer activity of berberine in the Ehrlich ascites carcinoma-bearing mice.

    Science.gov (United States)

    Jagetia, Ganesh Chandra; Baliga, Manjeshwar Shrinath

    2004-01-01

    The chemomodulatory activity of Alstonia scholaris extract (ASE) was studied in combination with berberine hydrochloride (BCL), a topoisomerase inhibitor, in Ehrlich ascites carcinoma-bearing mice. The tumor-bearing animals were injected with various doses of ASE, and 8 mg/kg of BCL (one-fifth of the 50% lethal dose) was combined with different doses of ASE (60-240 mg/kg). The combination of 180 mg/kg of ASE with 8 mg/kg of BCL showed the greatest antitumor effect; the number of tumor-free survivors was more, and the median survival time and the average survival time increased up to 47 and 40.5 days, respectively, when compared with either treatment alone. Similarly, when 180 mg/kg of ASE was combined with different doses of BCL (2-12 mg/kg), a dose-dependent increase in the anticancer activity was observed up to 8 mg/kg of BCL. However, a further increase in the BCL dose to 10 and 12 mg/kg resulted in toxic side effects. The best effect was observed when 180 mg/kg of ASE was combined with 6 or 8 mg/kg of BCL, where an increase in the antineoplastic activity was reported. The efficacy of the combination of 180 mg/kg of ASE was also tested with 6 mg/kg body weight of BCL in various stages of tumorigenesis, and it was effective when given in the early stages, although the efficiency decreased with an increase in the tumor developmental stages.

  11. 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.

  12. Preparation of RGD-modified Long Circulating Liposome Loading Matrine, and its in vitro Anti-cancer Effects

    Directory of Open Access Journals (Sweden)

    Xiao-yan Liu, Li-ming Ruan, Wei-wei Mao, Jin-Qiang Wang, You-qing Shen, Mei-hua Sui

    2010-01-01

    Full Text Available Aim: To prepare RGD-modified long circulating liposome (LCL loading matrine (RGD-M-LCL to improve the tumor-targeting and efficacy of matrine. Methods: LCL which was prepared with HSPC, cholesterol, DSPE-PEG2000 and DSPE-PEG-MAL was modified with an RGD motif confirmed by high performance liquid chromatography (HPLC. The encapsulation efficiency of RGD-M-LCL was also detected by HPLC. MTT assay was used to examine the effects of RGD-M-LCL on the proliferation of Bcap-37, HT-29 and A375 cells. The percentage of apoptotic cells and morphological changes in Bcap-37 cells treated with RGD-M-LCL were detected by Annexin-V-FITC/PI affinity assay and observed under light microscope, respectively. Results: Spherical or oval single-chamber particles of uniform sizes with little agglutination or adhesion were observed under transmission electronic microscope. The RGD motif was successfully coupled to the DSPE-PEG-MAL on liposomes, as confirmed by HPLC. An encapsulation efficiency of 83.13% was obtained when the drug-lipid molar ratio was 0.1, and the encapsulation efficiency was negatively related to the drug-lipid ratio in the range of 0.1~0.4, and to the duration of storage. We found that, compared with free matrine, RGD-M-LCL had much stronger in vitro activity, leading to anti-proliferative and pro-apoptotic effects against cancer cells (P<0.01. Conclusion: RGD-M-LCL, a novel delivery system for anti-cancer drugs, was successfully prepared, and we demonstrated that the use of this material could augment the effects of matrine on cancer cells in vitro.

  13. Investigation of the anti-cancer effect of quercetin on HepG2 cells in vivo

    Science.gov (United States)

    Li, Lin; Yao, Wenxiu; Xiong, Zhujuan; Zhou, Xiang

    2017-01-01

    Quercetin, a natural polyphenolic flavonoid compound, can inhibit the growth of several malignant cancers. However, the mechanism still remains unclear. Our previous findings have suggested that quercetin can significantly inhibit HepG2 cell proliferation and induce cell apoptosis in vitro. It can also affect cell cycle distribution and significantly decrease cyclin D1 expression. In this study, we investigated the anti-cancer effect of quercetin on HepG2 tumor-bearing nude mice and its effect on cyclin D1 expression in the tumor tissue. First, the nude murine tumor model was established by subcutaneous inoculation of HepG2 cells, then quercetin was administered intraperitoneally, and the mice injected with saline solution were used as controls. The daily behavior of the tumor-bearing mice was observed and differences in tumor growth and survival rate were monitored. The expression of cyclin D1 in isolated tumor sections was evaluated by immunohistochemistry. We found that HepG2 tumor became palpable in the mice one-week post-inoculation. Tumors in the control group grew rapidly and the daily behavior of the mice changed significantly, including listlessness, poor feeding and ataxia. The mice in quercetin-treated group showed delayed tumor growth, no significant changes in daily behavior, and the survival rate was significantly improved. Finally, we observed increased tumor necrosis and a lighter cyclin D1 staining with reduced staining areas. Our findings thus suggest that quercetin can significantly inhibit HepG2 cell proliferation, and this effect may be achieved through the regulation of cyclin D1 expression. PMID:28264020

  14. 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.

  15. Research Progress of Tea Anticancer Effects%茶叶的抗癌作用研究进展

    Institute of Scientific and Technical Information of China (English)

    陈勋; 贾尚智; 闵彩云; 金孝芳

    2011-01-01

    Scientific research indicated that dietary intake of tea may prevent and reduce the risk of different types of malignancies. Catechins,the major active component in green tea. could not only inhibit the assimilation of many carcinogens,but also act as a chemoprevention agent for cancers induced by gene mutation, immune system disorder and so on. In recent years, its underlying mechanism against carcinoma has attracted many researchers' attention, and prominent achievements have been made. In the present paper, we summarized anticancer effects of tea from four aspects, viz. animal tumor models,cell culture systems, epidemiological study and clinical trials, and also reviewed the research progress of its underlying mechanism, such as antioxidant effect, antimutagenic effect, induction of cell apoptosis and so on.%科学研究表明,饮茶对人类各种疾病有预防作用.儿茶素是茶叶中最主要的抗癌成分,不仅能够抑制人体对许多致癌物的吸收,而且对机体本身基因突变和免疫系统紊乱等引起的癌症有预防作用.近年来,茶叶抗癌机理成为研究的热点,取得了显著成效.从细胞水平,动物试验,流行病学调查和临床研究四个方面综述了茶叶的抗癌功效及其抗癌机理,即抗氧化作用,抗突变作用,诱导细胞凋亡等方面的研究进展.

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

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    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.

  17. Anticancer activity of Amauroderma rude.

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    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. 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.

  19. Anticancer effect of joboksansam, Korean wild ginseng germinated from bird feces

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    Jae Gwang Park

    2016-07-01

    Conclusion: Overall, our results strongly suggest that joboksansam powder has the potential to protect against cancer generation by direct cytotoxic effects on cancer cells resulting from suppression of cell survival signaling.

  20. 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

  1. Anticancer Effect of Ferulago Mughlea Peşmen (Apiaceae) on Cancer Cell Proliferation

    Science.gov (United States)

    Filiz, Bakar; Songül, Karakay; Bostanlık, Delimustafaoğlu; Gül, Fatma; Ceyda Sibel, Kılıç

    2016-01-01

    Ferulago W. Koch. (Apiaceae) genus is represented by approximately 50 taxa throughout the world. Ferulago species are known as “Çakşır” or “Çağşır” in Turkey and mostly known for their aphrodisiac effects. However recent reports emphasize the activity of various Ferulago species against cancer, as well. The aim of this study was to investigate the effect of lyophilized extract of F. mughlea Peşmen, a species endemic for Turkey, on cancer cell proliferation. For this purpose human prostate (PC-3) and colorectal (SW-480) carcinoma cells were used to evaluate the antiproliferative effects of Ferulago W. Koch and the measurements were performed via MTT test. Lyophilized extracts obtained from aerial parts and the roots exhibited potent inhibitor effects on cell proliferation. Aerial part of the plant inhibited the proliferation of SW-480 cell at 48th hour with a 0.119 mg/mL IC50 value. PMID:27980585

  2. Statins exhibit anticancer effects through modifications of the pAkt signaling pathway.

    Science.gov (United States)

    Miraglia, Erica; Högberg, Johan; Stenius, Ulla

    2012-03-01

    Statins are cholesterol lowering drugs that exhibit antitumor effects in several in vitro and in vivo models, and epidemiological studies indicate that statins prevent cancer. However, the molecular mechanism underlying the effects of statins still needs to be elucidated. We previously demonstrated that single doses of different statins rapidly affect Akt signaling via the purinergic receptor P2X7. In particular, statins down-regulated nuclear pAkt. Here, we report that long-term treatment of A549 cells with high concentrations of statins (15-75 µM) selects cell sub-populations exhibiting altered P2X receptor expression, signs of increased PTEN activity, enhanced PHLPP2, decreased PI3K p110β and inhibited downstream pAkt signaling. Furthermore, the nuclear accumulation of pAkt in response to insulin was inhibited in selected cells. Statin-selected cells displayed reduced proliferation rate and were more vulnerable to etoposide- and 5-fluorouracil-elicited cytotoxic effects. The stability of a selected phenotype (50 µM) was tested for three weeks in the absence of statins. This resulted in a reversal of some, but not all alterations. Importantly, the truncated nuclear insulin response was retained. We conclude that long-term treatment with high doses of statins selects cells exhibiting stable alterations in insulin-Akt signaling and which are vulnerable to DNA damage. Our studies strengthen the hypothesis that an altered Akt signaling has a role in chemopreventive effects of statins.

  3. Mitochondria-Mediated Anticancer Effects of Non-Thermal Atmospheric Plasma

    Science.gov (United States)

    Zhunussova, Aigul; Vitol, Elina A.; Polyak, Boris; Tuleukhanov, Sultan; Brooks, Ari D.; Sensenig, Richard; Friedman, Gary; Orynbayeva, Zulfiya

    2016-01-01

    Non-thermal atmospheric pressure plasma has attracted great interest due to its multiple potential biomedical applications with cancer treatment being among the most urgent. To realize the clinical potential of non-thermal plasma, the exact cellular and molecular mechanisms of plasma effects must be understood. This work aimed at studying the prostate cancer specific mechanisms of non-thermal plasma effects on energy metabolism as a central regulator of cell homeostasis and proliferation. It was found that cancer cells with higher metabolic rate initially are more resistant to plasma treated phosphate-buffered saline (PBS) since the respiratory and calcium sensitive signaling systems were not responsive to plasma exposure. However, dramatic decline of cancer oxidative phosphorylation developed over time resulted in significant progression of cell lethality. The normal prostate cells with low metabolic activity immediately responded to plasma treated PBS by suppression of respiratory functions and sustained elevation of cytosolic calcium. However, over time the normal cells start recovering their mitochondria functions, proliferate and restore the cell population. We found that the non-thermal plasma induced increase in intracellular ROS is of primarily non-mitochondrial origin. The discriminate non-thermal plasma effects hold a promise for clinical cancer intervention. PMID:27270230

  4. Mitochondria-Mediated Anticancer Effects of Non-Thermal Atmospheric Plasma.

    Directory of Open Access Journals (Sweden)

    Aigul Zhunussova

    Full Text Available Non-thermal atmospheric pressure plasma has attracted great interest due to its multiple potential biomedical applications with cancer treatment being among the most urgent. To realize the clinical potential of non-thermal plasma, the exact cellular and molecular mechanisms of plasma effects must be understood. This work aimed at studying the prostate cancer specific mechanisms of non-thermal plasma effects on energy metabolism as a central regulator of cell homeostasis and proliferation. It was found that cancer cells with higher metabolic rate initially are more resistant to plasma treated phosphate-buffered saline (PBS since the respiratory and calcium sensitive signaling systems were not responsive to plasma exposure. However, dramatic decline of cancer oxidative phosphorylation developed over time resulted in significant progression of cell lethality. The normal prostate cells with low metabolic activity immediately responded to plasma treated PBS by suppression of respiratory functions and sustained elevation of cytosolic calcium. However, over time the normal cells start recovering their mitochondria functions, proliferate and restore the cell population. We found that the non-thermal plasma induced increase in intracellular ROS is of primarily non-mitochondrial origin. The discriminate non-thermal plasma effects hold a promise for clinical cancer intervention.

  5. 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.

  6. Lupeol evokes anticancer effects in oral squamous cell carcinoma by inhibiting oncogenic EGFR pathway.

    Science.gov (United States)

    Rauth, Sanchita; Ray, Sudipta; Bhattacharyya, Sayantan; Mehrotra, Debapriya Ghosh; Alam, Neyaz; Mondal, Goutam; Nath, Partha; Roy, Asoke; Biswas, Jaydip; Murmu, Nabendu

    2016-06-01

    Epidermal growth factor receptor (EGFR) pathway is overexpressed in head and neck cancer (HNC). Lupeol, a natural triterpene (phytosterol found in fruits, vegetables, etc.), has been reported to be effective against multiple cancer indications. Here we investigate the antitumor effects of Lupeol and underlying mechanism in oral cancer. Lupeol-induced antitumor response was evaluated in two oral squamous cell carcinoma (OSCC) cell lines (UPCI:SCC131 and UPCI:SCC084) by viability (MTT), proliferation, and colony formation assays. Lupeol-mediated induction of apoptosis was examined by caspase 3/7 assay and flow cytometry. Effect of Lupeol on EGFR in the presence or absence of EGF was delineated by Western blot. The mRNA stability assay was performed to check the role of Lupeol on COX-2 mRNA regulation. Lupeol inhibited proliferation of OSCC cells in vitro by inducing apoptosis 48 h post treatment. Ligand-induced phosphorylation of EGFR and subsequent activation of its downstream molecules such as protein kinase B (PKB or AKT), I kappa B (IκB), and nuclear factor kappa B (NF-κB) was also found to be, in part, suppressed. Interestingly, Lupeol suppressed expression of COX-2 at mRNA and protein level in a time-dependent manner. Primary explants from oral squamous cell carcinoma tissues further confirmed significant inhibition of proliferation (Ki67) in Lupeol-treated explants as compared to untreated control at 48 h. Together these data suggest that Lupeol may act as a potent inhibitor of the EGFR signaling in OSCC and therefore imply its role in triggering antitumor efficacy.

  7. Ginger extract (Zingiber officinale has anti-cancer and anti-inflammatory effects on ethionine-induced hepatoma rats

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    Shafina Hanim Mohd Habib

    2008-01-01

    Full Text Available OBJECTIVE: To evaluate the effect of ginger extract on the expression of NFκB and TNF-α in liver cancer-induced rats. METHODS: Male Wistar rats were randomly divided into 5 groups based on diet: i control (given normal rat chow, ii olive oil, iii ginger extract (100mg/kg body weight, iv choline-deficient diet + 0.1% ethionine to induce liver cancer and v choline-deficient diet + ginger extract (100mg/kg body weight. Tissue samples obtained at eight weeks were fixed with formalin and embedded in paraffin wax, followed by immunohistochemistry staining for NFκB and TNF-α. RESULTS: The expression of NFκB was detected in the choline-deficient diet group, with 88.3 ± 1.83% of samples showing positive staining, while in the choline-deficient diet supplemented with ginger group, the expression of NFκB was significantly reduced, to 32.35 ± 1.34% (p<0.05. In the choline-deficient diet group, 83.3 ± 4.52% of samples showed positive staining of TNF-α, which was significantly reduced to 7.94 ± 1.32% (p<0.05 when treated with ginger. There was a significant correlation demonstrated between NFκB and TNF-α in the choline-deficient diet group but not in the choline-deficient diet treated with ginger extract group. CONCLUSION: In conclusion, ginger extract significantly reduced the elevated expression of NFκB and TNF-α in rats with liver cancer. Ginger may act as an anti-cancer and anti-inflammatory agent by inactivating NFκB through the suppression of the pro-inflammatory TNF-α.

  8. Anticancer effects of saponin and saponin–phospholipid complex of Panax notoginseng grown in Vietnam

    OpenAIRE

    Thu Dang Kim; Hai Nguyen Thanh; Duong Nguyen Thuy; Loi Vu Duc; Thu Vu Thi; Hung Vu Manh; Patcharee Boonsiri; Tung Bui Thanh

    2016-01-01

    Objective: To evaluate the antitumor activity both in vitro and in vivo of saponin–phospholipid complex of Panax notoginseng. Methods: The in vitro cytotoxic effect of saponins extract and saponin–phospholipid complex against human lung cancer NCI-H460 and breast cancer cell lines BT474 was examined using MTS assay. For in vivo evaluation of antitumor potential, saponin and saponin–phospholipid complex were administered orally in rats induced mammary carcinogenesis by 7,12-dimethylbenz(a)a...

  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. A PRELIMINARY STUDY OF THE ANTI-CANCER EFFECT OF TANSHINONE ON HEPATIC CANCER AND ITS MECHANISM OF ACTION IN MICE

    Institute of Scientific and Technical Information of China (English)

    Wang Xiujie; Yuan Shulan; Wang Chaojun; Huang Renmin; Li Yuqiong

    1998-01-01

    Objective: There were some experimental researches in vitro, which showed that tanshinonoe (Tan)had cytotoxic activities against some cancer cell lines. But there was no report of anti-cancer activity of Tan in vivo.This experimental study was performed to confirm the anti-cancer activity of Tan in vivo. Methods: Hepatic carcinoma H22 bearing mice were treated with DMSO, 5-Fu, and Tan, at the end of experiment, the mice were sacrificed, tumor tissues were separated and weighed, and the tumor inhibitory rate was calculated, 3 times of the same experiments were performed. The proliferating kinetics of hepatic carcinoma H22 cells in mice was measured by bromodeoxyuridine labeling in vivo and immunohistochemical staining of the proliferating cell nuclear antigen (PCNA) in tumor tissues. Results: The tumor inhibitory rates of Tan were 50.0%, 38.5%, and 40.6% in 3 experiments, respectively, compared with those of the DMSO-treated control groups, the differences were significant statistically (P<0.01). The Brdu labeling and PCNA positive cells were 51.8± 7.9 and 451.1± 26.1, respectively, which were significantly lower than those of controls (84.4± 24.3, 694.8±117.1) (P<0.01). Conclusion:Tan had anti-cancer effect on hepatic carcinoma in vivo;The mechanisms of action might be associated with inhibition of DNA synthesis, PCNA expression and DNA polymerase δ activity of tumor cells.

  11. 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.

  12. Modulation of anticancer drug toxicity by solcoseryl.

    Science.gov (United States)

    Sołtysiak-Pawluczuk, D; Jedrych, A; Jastrzebski, Z; Czyzewska-Szafran, H; Danysz, A

    1991-01-01

    The studies of the effect of solcoseryl on toxicity of selected anticancer drugs were performed in mice. The observed differential influence of solcoseryl was dependent on the type of anticancer drug as well as on the schedule of solcoseryl administration. The protective effect of the biostimulator was noticed exclusively against 5-FU toxicity. The results of our studies could provide possible implications for therapeutic approach.

  13. A support vector machine model provides an accurate transcript-level-based diagnostic for major depressive disorder

    Science.gov (United States)

    Yu, J S; Xue, A Y; Redei, E E; Bagheri, N

    2016-01-01

    Major depressive disorder (MDD) is a critical cause of morbidity and disability with an economic cost of hundreds of billions of dollars each year, necessitating more effective treatment strategies and novel approaches to translational research. A notable barrier in addressing this public health threat involves reliable identification of the disorder, as many affected individuals remain undiagnosed or misdiagnosed. An objective blood-based diagnostic test using transcript levels of a panel of markers would provide an invaluable tool for MDD as the infrastructure—including equipment, trained personnel, billing, and governmental approval—for similar tests is well established in clinics worldwide. Here we present a supervised classification model utilizing support vector machines (SVMs) for the analysis of transcriptomic data readily obtained from a peripheral blood specimen. The model was trained on data from subjects with MDD (n=32) and age- and gender-matched controls (n=32). This SVM model provides a cross-validated sensitivity and specificity of 90.6% for the diagnosis of MDD using a panel of 10 transcripts. We applied a logistic equation on the SVM model and quantified a likelihood of depression score. This score gives the probability of a MDD diagnosis and allows the tuning of specificity and sensitivity for individual patients to bring personalized medicine closer in psychiatry. PMID:27779627

  14. Construction of pancreatic cancer double-factor regulatory network based on chip data on the transcriptional level.

    Science.gov (United States)

    Zhao, Li-Li; Zhang, Tong; Liu, Bing-Rong; Liu, Tie-Fu; Tao, Na; Zhuang, Li-Wei

    2014-05-01

    Transcription factor (TF) and microRNA (miRNA) have been discovered playing crucial roles in cancer development. However, the effect of TFs and miRNAs in pancreatic cancer pathogenesis remains vague. We attempted to reveal the possible mechanism of pancreatic cancer based on transcription level. Using GSE16515 datasets downloaded from gene expression omnibus database, we first identified the differentially expressed genes (DEGs) in pancreatic cancer by the limma package in R. Then the DEGs were mapped into DAVID to conduct the kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. TFs and miRNAs that DEGs significantly enriched were identified by Fisher's test, and then the pancreatic cancer double-factor regulatory network was constructed. In our study, total 1117 DEGs were identified and they significantly enriched in 4 KEGG pathways. A double-factor regulatory network was established, including 29 DEGs, 24 TFs, 25 miRNAs. In the network, LAMC2, BRIP1 and miR155 were identified which may be involved in pancreatic cancer development. In conclusion, the double-factor regulatory network was found to play an important role in pancreatic cancer progression and our results shed new light on the molecular mechanism of pancreatic cancer.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. 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.

  17. Aqueous Solubility and Degradation Kinetics of the Phytochemical Anticancer Thymoquinone; Probing the Effects of Solvents, pH and Light

    Directory of Open Access Journals (Sweden)

    Jumah Masoud M. Salmani

    2014-05-01

    Full Text Available Thymoquinone (TQ is a potent anticancer phytochemical with confirmed in vitro efficacy. Its clinical use has not yet established, and very few reports have documented its formulation. There also are no reports about the aqueous solubility and stability of this valuable drug, despite their direct correlation with the in vivo efficacy. In the current research, we have established and validated a stability-indicating HPLC method for the detection of TQ and its degradation products under different conditions. We then investigated the solubility and stability profiles of TQ in aqueous solutions. The stability study was aimed to determine the effect of pH, solvent type and light on the degradation process of TQ, along with the investigation of the kinetics of this degradation. The solubility of TQ varied in different aqueous solvents, and might be compromised due to stability issues. However, these findings confirm that the aqueous solubility is not the major obstacle for the drug formulations mainly due to the considerable water solubility (>500 μg/mL that may be enough to exert pharmacologic effects if administered via parenteral route. Stability study results showed a very low stability profile of TQ in all the aqueous solutions with rapid degradation that varied with solvent type. The study of the degradation kinetics showed a significant effect of pH on the degradation process. The process followed first order kinetics at more acidic and alkaline pH values, and second order kinetics at pH 5–7.4, regardless of the solvent type. The results also expressed that light has a greater impact on the stability of TQ as a shorter period of exposure led to severe degradation, independent of the solution pH and solvent type. Our results also addressed some discrepancies in previously published researches regarding the formulation and quantification of TQ with suggested solutions. Overall, the current study concludes that TQ is unstable in aqueous

  18. The anti-cancer effects of carotenoids and other phytonutrients resides in their combined activity.

    Science.gov (United States)

    Linnewiel-Hermoni, Karin; Khanin, Marina; Danilenko, Michael; Zango, Gabriel; Amosi, Yaara; Levy, Joseph; Sharoni, Yoav

    2015-04-15

    Epidemiological studies have consistently shown that regular consumption of fruits and vegetables is strongly associated with reduced risk of developing chronic diseases, such as cancer. It is now accepted that the actions of any specific phytonutrient alone do not explain the observed health benefits of diets rich in fruits and vegetables as nutrients that were taken alone in clinical trials did not show consistent preventive effects. The considerable cost and complexity of such clinical trials requires prudent selection of combinations of ingredients rather than single compounds. Indeed, synergistic inhibition of prostate and mammary cancer cell growth was evident when using combinations of low concentrations of various carotenoids or carotenoids with retinoic acid and the active metabolite of vitamin-D. In this study we aimed to develop simple and sensitive in vitro methods which provide information on potent combinations suitable for inclusion in clinical studies for cancer prevention. We, thus, used reporter gene assays of the transcriptional activity of the androgen receptor in hormone-dependent prostate cancer cells and of the electrophile/antioxidant response element (EpRE/ARE) transcription system. We found that combinations of several carotenoids (e.g., lycopene, phytoene and phytofluene), or carotenoids and polyphenols (e.g., carnosic acid and curcumin) and/or other compounds (e.g., vitamin E) synergistically inhibit the androgen receptor activity and activate the EpRE/ARE system. The activation of EpRE/ARE was up to four fold higher than the sum of the activities of the single ingredients, a robust hallmark of synergy. Such combinations can further be tested in the more complex in vivo models and human studies.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. 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

  1. SOME IMPORTANT ANTICANCER HERBS: A REVIEW

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    Pandey Govind

    2011-07-01

    Full Text Available A great deal of pharmaceutical research has considerably improved the quality of herbal drugs used against various types of cancer. With the advanced knowledge of molecular science and the refinement in isolation and structure elucidation techniques, we are in a much better position now to identify various anticancer herbs. Scientists all over the world are concentrating on the use of herbs to boost immune system of the body against cancer. Scientists have contributed for a number of years to identify hundreds of anticancer herbs, and developed various herbal formulations from their active principles that inhibit growth and spread of cancer without any side effect. Such herbs possess anticancer, immunoenhancing, antiangiogenesis, antioxidant and antimutagenic properties. They inhibit growth and spread of cancer by modulating the activity of hormones, enzymes and other biological factors. The therapeutic effect of these herbs is executed by the complex synergistic interaction among their various active principles. Some important anticancer herbs have been discussed here.

  2. 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.

  3. Effects of JS-K, a novel anti-cancer nitric oxide prodrug, on gene expression in human hepatoma Hep3B cells.

    Science.gov (United States)

    Dong, Ray; Wang, Xueqian; Wang, Huan; Liu, Zhengyun; Liu, Jie; Saavedra, Joseph E

    2017-04-01

    JS-K is a novel anticancer nitric oxide (NO) prodrug effective against a variety of cancer cells, including the inhibition of AM-1 hepatoma cell growth in rats. To further evaluate anticancer effects of JS-K, human hepatoma Hep3B cells were treated with JS-K and the compound control JS-43-126 at various concentrations (0-100μM) for 24h, and cytotoxicity was determined by the MTS assay. The compound control JS-43-126 was not cytotoxic to Hep3B cells at concentrations up to 100μM, while the LC50 for JS-K was about 10μM. To examine the molecular mechanisms of antitumor effects of JS-K, Hep3B cells were treated with 1-10μM of JS-K for 24h, and then subjected to gene expression analysis via real time RT-PCR and protein immunostain via confocal images. JS-K is a GST-α targeting NO prodrug, and decreased immunostaining for GST-α was associated with JS-K treatment. JS-K activated apoptosis pathways in Hep3B cells, including induction of caspase-3, caspase-9, Bax, TNF-α, and IL-1β, and immunostaining for caspase-3 was intensified. The expressions of thrombospondin-1 (TSP-1) and the tissue inhibitors of metalloproteinase-1 (TIMP-1) were increased by JS-K at both transcript and protein levels. JS-K treatment also increased the expression of differentiation-related genes CD14 and CD11b, and depressed the expression of c-myc in Hep3B cells. Thus, multiple molecular events appear to be associated with anticancer effects of JS-K in human hepatoma Hep3B cells, including activation of genes related to apoptosis and induction of genes involved in antiangiogenesis and tumor cell migration.

  4. The sae locus of Staphylococcus aureus controls exoprotein synthesis at the transcriptional level.

    Science.gov (United States)

    Giraudo, A T; Cheung, A L; Nagel, R

    1997-07-01

    Agr and sar are known regulatory loci of Staphylococcus aureus that control the production of several extracellular and cell-wall-associated proteins. A pleiotropic insertional mutation in S. aureus, designated sae, that leads to the production of drastically diminished levels of alpha- and beta-hemolysins and coagulase and slightly reduced levels of protein A has been described. The study of the expression of the genes coding for these exoproteins in the sae::Tn551 mutant (carried out in this work by Northern blot analyses) revealed that the genes for alpha- and beta-hemolysins (hla and hlb) and coagulase (coa) are not transcribed and that the gene for protein A (spa) is transcribed at a somewhat reduced level. These results indicate that the sae locus regulates these exoprotein genes at the transcriptional level. Northern blot analyses also show that the sae mutation does not affect the expression of agr or sar regulatory loci. An sae::Tn551 agr::tetM double mutant has been phenotypically characterized as producing reduced or null levels of alpha-, beta-, and delta-hemolysins, coagulase, and high levels of protein A. Northern blot analyses carried out in this work with the double mutant revealed that hla, hlb, hld, and coa genes are not transcribed, while spa is transcribed at high levels. The fact that coa is not expressed in the sae agr mutant, as in the sae parental strain, while spa is expressed at the high levels characteristic of the agr parental strain, suggests that sae and agr interact in a complex way in the control of the expression of the genes of several exoproteins.

  5. Characterization and in vitro studies of the anticancer effect of oxidized carbon nanotubes functionalized with betulinic acid

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    Tan JM

    2014-11-01

    studies revealed that MWCNT-BA at concentrations <50 µg/mL expressed no cytotoxicity effects for mouse embryo fibroblast cells after 72 hours of treatment. The anticancer activity of MWCNT-BA was observed to be more sensitive to human lung cancer cell line when compared with human liver cancer cell line, with half maximal inhibitory concentration values of 2.7 and 11.0 µg/mL, respectively. Our findings form a fundamental platform for further investigation of the MWCNT-BA formulation against different types of cancer cells. Keywords: multiwalled carbon nanotubes (MWCNTs, drug delivery, controlled release, cytotoxicity, A549 cell line, HepG2 cell line

  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

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    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.

  7. Transcription levels of endothelin-1 and endothelin receptors are associated with age and leaflet location in porcine mitral valves

    DEFF Research Database (Denmark)

    Pedersen, Lotte Gam; Offenberg, Hanne Kjær; Moesgaard, Sophia Gry;

    2007-01-01

    The aim of the study was to investigate the expression levels of endothelin-1 (ET-1) and ETA and ETB receptors (ETA-R and ETB-R) in porcine mitral valves and associate the transcription levels to age, leaflet location and deposition of mucopolysaccharides (MPS). Tissue samples from the chordal an...

  8. Anticancer molecular mechanisms of resveratrol

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    Elena Maria Varoni

    2016-04-01

    Full Text Available Resveratrol is a pleiotropic phytochemical belonging to the stilbene family. Despite 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; immune-surveillance and hormone signaling. Resveratrol also showed a promising role to counteract multi-drug 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.

  9. 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.

  10. Extremely low-frequency electromagnetic fields affect transcript levels of neuronal differentiation-related genes in embryonic neural stem cells.

    Directory of Open Access Journals (Sweden)

    Qinlong Ma

    Full Text Available Previous studies have reported that extremely low-frequency electromagnetic fields (ELF-EMF can affect the processes of brain development, but the underlying mechanism is largely unknown. The proliferation and differentiation of embryonic neural stem cells (eNSCs is essential for brain development during the gestation period. To date, there is no report about the effects of ELF-EMF on eNSCs. In this paper, we studied the effects of ELF-EMF on the proliferation and differentiation of eNSCs. Primary cultured eNSCs were treated with 50 Hz ELF-EMF; various magnetic intensities and exposure times were applied. Our data showed that there was no significant change in cell proliferation, which was evaluated by cell viability (CCK-8 assay, DNA synthesis (Edu incorporation, average diameter of neurospheres, cell cycle distribution (flow cytometry and transcript levels of cell cycle related genes (P53, P21 and GADD45 detected by real-time PCR. When eNSCs were induced to differentiation, real-time PCR results showed a down-regulation of Sox2 and up-regulation of Math1, Math3, Ngn1 and Tuj1 mRNA levels after 50 Hz ELF-EMF exposure (2 mT for 3 days, but the percentages of neurons (Tuj1 positive cells and astrocytes (GFAP positive cells were not altered when detected by immunofluorescence assay. Although cell proliferation and the percentages of neurons and astrocytes differentiated from eNSCs were not affected by 50 Hz ELF-EMF, the expression of genes regulating neuronal differentiation was altered. In conclusion, our results support that 50 Hz ELF-EMF induce molecular changes during eNSCs differentiation, which might be compensated by post-transcriptional mechanisms to support cellular homeostasis.

  11. Acupuncture as anticancer treatment?

    Science.gov (United States)

    Kilian-Kita, Aneta; Püsküllüoglu, Mirosława; Krzemieniecki, Krzysztof

    2017-01-01

    The mystery of Traditional Chinese Medicine has been attracting people for years. Acupuncture, ranked among the most common services of Complementary and Alternative Medicine, has recently gained a lot of interest in the scientific world. Contemporary researchers have been continuously trying to shed light on its possible mechanism of action in human organism. Numerous studies pertaining to acupuncture’s application in cancer symptoms or treatment-related side effects management have already been published. Moreover, since the modern idea of acupuncture’s immunomodulating effect seems to be promising, scientists have propounded a concept of its potential application as part of direct anti-tumor therapy. In our previous study we summarized possible use of acupuncture in management of cancer symptoms and treatment-related ailments, such as chemotherapy-induced nausea and vomiting, pain, xerostomia, vasomotor symptoms, neutropenia, fatigue, anxiety, insomnia, lymphoedema after mastectomy and peripheral neuropathy. This article reviews the studies concerning acupuncture as a possible tool in modern anticancer treatment. PMID:28239282

  12. L-carnitine Mediated Reduction in Oxidative Stress and Alteration in Transcript Level of Antioxidant Enzymes in Sheep Embryos Produced In Vitro.

    Science.gov (United States)

    Mishra, A; Reddy, I J; Gupta, P S P; Mondal, S

    2016-04-01

    The objective of this study was to find out the effect of L-carnitine on oocyte maturation and subsequent embryo development, with L-carnitine-mediated alteration if any in transcript level of antioxidant enzymes (GPx, Cu/Zn-SOD (SOD1) and Mn-SOD (SOD2) in oocytes and developing sheep embryos produced in vitro. Different concentrations of L-carnitine (0 mm, 2.5 mm, 5 mm, 7.5 mm and 10 mm) were used in maturation medium. Oocytes matured with 10 mm L-carnitine showed significantly (p carnitine were not significantly different. Maturation rate was not influenced by supplementation of any experimental concentration of L-carnitine. There was a significant (p carnitine-treated oocytes and embryos than control group. Antioxidant effect of L-carnitine was proved by culturing oocytes and embryos with H2O2 in the presence of L-carnitine which could be able to protect oocytes and embryos from H2O2-induced oxidative damage. L-carnitine supplementation significantly (p carnitine supplementation during in vitro maturation reduces oxidative stress-induced embryo toxicity by decreasing intracellular ROS and increasing intracellular GSH that in turn improved developmental potential of oocytes and embryos and alters transcript level of antioxidant enzymes.

  13. 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.

  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.

  15. Targeted anticancer therapy: overexpressed receptors and nanotechnology.

    Science.gov (United States)

    Akhtar, Mohd Javed; Ahamed, Maqusood; Alhadlaq, Hisham A; Alrokayan, Salman A; Kumar, Sudhir

    2014-09-25

    Targeted delivery of anticancer drugs to cancer cells and tissues is a promising field due to its potential to spare unaffected cells and tissues, but it has been a major challenge to achieve success in these therapeutic approaches. Several innovative approaches to targeted drug delivery have been devised based on available knowledge in cancer biology and on technological advancements. To achieve the desired selectivity of drug delivery, nanotechnology has enabled researchers to design nanoparticles (NPs) to incorporate anticancer drugs and act as nanocarriers. Recently, many receptor molecules known to be overexpressed in cancer have been explored as docking sites for the targeting of anticancer drugs. In principle, anticancer drugs can be concentrated specifically in cancer cells and tissues by conjugating drug-containing nanocarriers with ligands against these receptors. Several mechanisms can be employed to induce triggered drug release in response to either endogenous trigger or exogenous trigger so that the anticancer drug is only released upon reaching and preferentially accumulating in the tumor tissue. This review focuses on overexpressed receptors exploited in targeting drugs to cancerous tissues and the tumor microenvironment. We briefly evaluate the structure and function of these receptor molecules, emphasizing the elegant mechanisms by which certain characteristics of cancer can be exploited in cancer treatment. After this discussion of receptors, we review their respective ligands and then the anticancer drugs delivered by nanotechnology in preclinical models of cancer. Ligand-functionalized nanocarriers have delivered significantly higher amounts of anticancer drugs in many in vitro and in vivo models of cancer compared to cancer models lacking such receptors or drug carrying nanocarriers devoid of ligand. This increased concentration of anticancer drug in the tumor site enabled by nanotechnology could have a major impact on the efficiency of cancer

  16. Detecting the effect of targeted anti-cancer medicines on single cancer cells using a poly-silicon wire ion sensor integrated with a confined sensitive window.

    Science.gov (United States)

    Wu, You-Lin; Hsu, Po-Yen; Hsu, Chung-Ping; Lin, Jing-Jenn

    2012-10-01

    A mold-cast polydimethylsiloxane (PDMS) confined window was integrated with a poly-silicon wire (PSW) ion sensor. The PSW sensor surface inside the confined window was coated with a 3-aminopropyltriethoxysilane (γ-APTES) sensitive layer which allowed a single living cell to be cultivated. The change in the microenvironment due to the extracellular acidification of the single cell could then be determined by measuring the current flowing through the PSW channel. Based on this, the PSW sensor integrated with a confined sensitive window was used to detect the apoptosis as well as the effect of anti-cancer medicines on the single living non-small-lung-cancer (NSLC) cells including lung adenocarcinoma cancer cells A549 and H1299, and lung squamous-cell carcinoma CH27 cultivated inside the confined window. Single human normal cells including lung fibroblast cells WI38, lung fibroblast cells MRC5, and bronchial epithelium cell Beas-2B were tested for comparison. Two targeted anti-NSCLC cancer medicines, Iressa and Staurosporine, were used in the present study. It was found that the PSW sensor can be used to accurately detect the apoptosis of single cancer cells after the anti-cancer medicines were added. It was also found that Staurosporine is more effective than Iressa in activating the apoptosis of cancer cells.

  17. 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.

  18. 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

  19. Phytochemicals of Aristolochia tagala and Curcuma caesia exert anticancer effect by tumor necrosis factor-α-mediated decrease in nuclear factor kappaB binding activity

    Science.gov (United States)

    Hadem, Khetbadei Lysinia Hynniewta; Sharan, Rajeshwar Nath; Kma, Lakhan

    2015-01-01

    analysis revealed the presence of phenolic compounds in CC and indicated the presence of anthocynidin 3-glycosides, 6-hydroxylated flavonols, some flavones and chalcone glycosides in AT and also confirmed the presence of compounds such as terpenes, phenols, steroids, and other organic compounds in CC and presence of flavonoids in AT. In vivo studies carried out in BALB/c mice showed that exposure to DEN caused an increase in TNF-α and NF-κB binding activity. The HPE (CC or AT) was seen to revert this effect. Conclusions: The current paper documents the antioxidant, anti-inflammatory, and anticancer activity of the two extracts probably through TNF-α-mediated decrease in NF-κB binding activity. The active components of AT and CC may act as the potential anticancer agents in hepatocellular carcinoma and warrants further investigation. PMID:26792956

  20. An attempt to evaluate the effect of vitamin K3 using as an enhancer of anticancer agents.

    Science.gov (United States)

    Matzno, Sumio; Yamaguchi, Yuka; Akiyoshi, Takeshi; Nakabayashi, Toshikatsu; Matsuyama, Kenji

    2008-06-01

    The possibility of vitamin K3 (VK3) as an anticancer agent was assessed. VK3 dose-dependently diminished the cell viability (measured as esterase activity) with IC50 of 13.7 microM and Hill coefficient of 3.1 in Hep G2 cells. It also decreased the population of S phase and arrested cell cycle in the G2/M phase in a dose-dependent manner. G2/M arrest was regulated by the increment of cyclin A/cdk1 and cyclin A/cdk2 complex, and contrasting cyclin B/cdk1 complex decrease. Finally, combined application demonstrated that VK3 significantly enhanced the cytotoxicity of etoposide, a G2 phase-dependent anticancer agent, whereas it reduced the cytotoxic activity of irinotecan, a S phase-dependent agent. These findings suggest that VK3 induces G2/M arrest by inhibition of cyclin B/cdk1 complex formation, and is thus useful as an enhancer of G2 phase-dependent drugs in hepatic cancer chemotherapy.

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

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    Audrey C A Cleuren

    Full Text Available Obesity is associated with a hypercoagulable state and increased risk for thrombotic cardiovascular events.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.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.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.Changes in dietary fat content rapidly alter the mouse plasma coagulation profile, thereby preceding plasma metabolic changes, which

  2. Analysis of the Total Biflavonoids Extract from Selaginella doederleinii by HPLC-QTOF-MS and Its In Vitro and In Vivo Anticancer Effects

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    Hong Yao

    2017-02-01

    Full Text Available Selaginella doederleinii Hieron has been traditionally used as a folk antitumor herbal medicine in China. In this paper, the phytochemical components of the total biflavonoids extract from S. doederleinii were studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS in negative ion mode, and their in vitro and in vivo anticancer effects were evaluated. Four types of biflavonoids from S. doederleinii, including IC3′–IIC8′′, IC3′–IIC6′′, IC3′–IIC3′′′, and C–O linked biflavonoids were examined originally using QTOF MS/MS. The fragmentation behavior of IC3′–IIC3′′′ linked biflavonoids was reported for the first time. A total of twenty biflavonoids were identified or tentatively characterized and eight biflavonoids were found from S. doederleinii for the first time. Furthermore, the 3-(4,5-Dimethyl-2-thizolyl-2,5-diphenyltertazolium bromide (MTT assay and xenograft model of mouse lewis lung cancer(LLC in male C57BL/6 mice revealed favorable anticancer properties of the total biflavonoids extracts from S. doederleinii. The results of this work could provide useful knowledge for the identification of biflavonoids in herbal samples and further insights into the chemopreventive function of this plant.

  3. 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.

  4. 3-Substituted-4-hydroxycoumarin as a new scaffold with potent CDK inhibition and promising anticancer effect: Synthesis, molecular modeling and QSAR studies.

    Science.gov (United States)

    Abdel Latif, Nehad A; Batran, Rasha Z; Khedr, Mohammed A; Abdalla, Mohamed M

    2016-08-01

    A new series of 3-substituted-4-hydroxycoumarin derivatives was designed, synthesized, and evaluated for CDK inhibiting and anticancer activities. All the synthesized target compounds showed remarkably high affinity and selectivity towards CDK1B, compared to flavopiridol, with Ki values in the low nanomolar range (Ki=0.35-0.88nM). Most of them elicited considerable inhibiting effect against CDK9T1 (Ki=3.26-23.45nM). Moreover, all the target compounds were tested in vitro against eighteen types of human tumor cell lines. The hydrazone 3a, N-phenylpyrazoline derivative 6b and 2-aminopyridyl-3-carbonitrile derivative 8c were the most potent anticancer agents against MCF-7 breast cancer cell line (IC50=0.21, 0.21 and 0.23nM, respectively). The target compounds 3a, 6b and 8c were further evaluated in MCF-7 breast cancer mouse xenograft model and showed in vivo efficacy at 10mg/kg dose. The docking study confirmed a unique binding mode in the active site of CDK1B with better score than flavopiridol. Quantitative structure activity relationship study was done and revealed a highly predictive power R(2) of 0.81.

  5. Altered transcription levels of endocrine associated genes in two fisheries species collected from the Great Barrier Reef catchment and lagoon.

    Science.gov (United States)

    Kroon, Frederieke J; Hook, Sharon E; Jones, Dean; Metcalfe, Suzanne; Henderson, Brent; Smith, Rachael; Warne, Michael St J; Turner, Ryan D; McKeown, Adam; Westcott, David A

    2015-03-01

    The Great Barrier Reef (GBR) is chronically exposed to agricultural run-off containing pesticides, many of which are known endocrine disrupting chemicals (EDCs). Here, we measure mRNA transcript abundance of two EDC biomarkers in wild populations of barramundi (Lates calcarifer) and coral trout (Plectropomus leopardus and Plectropomus maculatus). Transcription levels of liver vitellogenin (vtg) differed significantly in both species amongst sites with different exposures to agricultural run-off; brain aromatase (cyp19a1b) revealed some differences for barramundi only. Exposure to run-off from sugarcane that contains pesticides is a likely pathway given (i) significant associations between barramundi vtg transcription levels, catchment sugarcane land use, and river pesticide concentrations, and (ii) consistency between patterns of coral trout vtg transcription levels and pesticide distribution in the GBR lagoon. Given the potential consequences of such exposure for reproductive fitness and population dynamics, these results are cause for concern for the sustainability of fisheries resources downstream from agricultural land uses.

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

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    Rachel M Taylor

    Full Text Available 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.

  7. 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.

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

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    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

  9. Anticancer Effects of a New SIRT Inhibitor, MHY2256, against Human Breast Cancer MCF-7 Cells via Regulation of MDM2-p53 Binding.

    Science.gov (United States)

    Park, Eun Young; Woo, Youngwoo; Kim, Seong Jin; Kim, Do Hyun; Lee, Eui Kyung; De, Umasankar; Kim, Kyeong Seok; Lee, Jaewon; Jung, Jee H; Ha, Ki-Tae; Choi, Wahn Soo; Kim, In Su; Lee, Byung Mu; Yoon, Sungpil; Moon, Hyung Ryong; Kim, Hyung Sik

    2016-01-01

    The sirtuins (SIRTs), a family of NAD(+)-dependent class III histone deacetylase, are involved in various biological processes including cell survival, division, senescence, and metabolism via activation of the stress-response pathway. Recently, inhibition of SIRTs has been considered a promising anticancer strategy, but their precise mechanisms of action are not well understood. In particular, the relevance of p53 to SIRT-induced effects has not been fully elucidated. We investigated the anticancer effects of a novel SIRT inhibitor, MHY2256, and its efficacy was compared to that of salermide in MCF-7 (wild-type p53) and SKOV-3 (null-type p53) cells. Cell viability, SIRT1 enzyme activity, cell cycle regulation, apoptosis, and autophagic cell death were measured. We compared sensitivity to cytotoxicity in MCF-7 and SKOV-3 cells. MHY2256 significantly decreased the viability of MCF-7 (IC50, 4.8 μM) and SKOV-3 (IC50, 5.6 μM) cells after a 48 h treatment period. MHY2256 showed potent inhibition (IC50, 0.27 mM) against SIRT1 enzyme activity compared with nicotinamide (IC50, >1 mM). Moreover, expression of SIRT (1, 2, or 3) protein levels was significantly reduced by MHY2256 treatment in both MCF-7 and SKOV-3 cells. Flow cytometry analysis revealed that MHY2256 significantly induced cell cycle arrest in the G1 phase, leading to an effective increase in apoptotic cell death in MCF-7 and SKOV-3 cells. A significant increase in acetylated p53, a target protein of SIRT, was observed in MCF-7 cells after MHY2256 treatment. MHY2256 up-regulated LC3-II and induced autophagic cell death in MCF-7 cells. Furthermore, MHY2256 markedly inhibited tumor growth in a tumor xenograft model of MCF-7 cells. These results suggest that a new SIRT inhibitor, MHY2256, has anticancer activity through p53 acetylation in MCF-7 human breast cancer cells.

  10. The influence of p53 mutation status on the anti-cancer effect of cisplatin in oral squamous cell carcinoma cell lines

    Science.gov (United States)

    2016-01-01

    Objectives The purpose of this study was to evaluate the anti-cancer activity of cisplatin by studying its effects on cell viability and identifying the mechanisms underlying the induction of cell cycle arrest and apoptosis on oral squamous cell carcinoma (OSCC) cell lines with varying p53 mutation status. Materials and Methods Three OSCC cell lines, YD-8 (p53 point mutation), YD-9 (p53 wild type), and YD-38 (p53 deletion) were used. To determine the cytotoxic effect of cisplatin, MTS assay was performed. The cell cycle alteration and apoptosis were analyzed using flow cytometry. Western blot analysis was used to detect the expression of cell cycle alteration- or apoptosis-related proteins as well as p53. Results Cisplatin showed a time- and dose-dependent anti-proliferative effect in all cell lines. Cisplatin induced G2/M cell accumulation in the three cell lines after treatment with 0.5 and 1.0 µg/mL of cisplatin for 48 hours. The proportion of annexin V-FITC-stained cells increased following treatment with cisplatin. The apoptotic proportion was lower in the YD-38 cell line than in the YD-9 or YD-8 cell lines. Also, immunoblotting analysis indicated that p53 and p21 were detected only in YD-8 and YD-9 cell lines after cisplatin treatment. Conclusion In this study, cisplatin showed anti-cancer effects via G2/M phase arrest and apoptosis, with some difference among OSCC cell lines. The mutation status of p53 might have influenced the difference observed among cell lines. Further studies on p53 mutation status are needed to understand the biological behavior and characteristics of OSCCs and to establish appropriate treatment. PMID:28053903

  11. 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

    2016-06-01

    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.

  12. Anticancer activity of Carica papaya: a review.

    Science.gov (United States)

    Nguyen, Thao T T; Shaw, Paul N; Parat, Marie-Odile; Hewavitharana, Amitha K

    2013-01-01

    Carica papaya is widely cultivated in tropical and subtropical countries and is used as food as well as traditional medicine to treat a range of diseases. Increasing anecdotal reports of its effects in cancer treatment and prevention, with many successful cases, have warranted that these pharmacological properties be scientifically validated. A bibliographic search was conducted using the key words "papaya", "anticancer", and "antitumor" along with cross-referencing. No clinical or animal cancer studies were identified and only seven in vitro cell-culture-based studies were reported; these indicate that C. papaya extracts may alter the growth of several types of cancer cell lines. However, many studies focused on specific compounds in papaya and reported bioactivity including anticancer effects. This review summarizes the results of extract-based or specific compound-based investigations and emphasizes the aspects that warrant future research to explore the bioactives in C. papaya for their anticancer activities.

  13. 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

    2015-01-01

    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. PMID:26074488

  14. Purple bamboo salt has anticancer activity in TCA8113 cells in vitro and preventive effects on buccal mucosa cancer in mice in vivo.

    Science.gov (United States)

    Zhao, Xin; Deng, Xiaoxiao; Park, Kun-Young; Qiu, Lihua; Pang, Liang

    2013-02-01

    Bamboo salt is a traditional healthy salt known in Korea. The in vitro anticancer effects of the salt were evaluated using a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay in TCA8113 human tongue carcinoma cells. At 1% concentration, the growth inhibitory rate of purple bamboo salt was 61% higher than that of sea salt (27%). Apoptosis analysis of the cancer cells was carried out using 4,6-diamidino-2-phenylindole (DAPI) staining to investigate the mechanism of the anticancer effects in tongue carcinoma cells. Purple bamboo salt induced a stronger apoptotic effect than sea salt. An Institute of Cancer Research (ICR) mouse buccal mucosa cancer model was established by injecting mice with U14 squamous cell carcinoma cells. Following injection, the wound at the injection site was smeared with salt samples. It was observed that the tumor volumes for the group treated with purple bamboo salt were smaller than those from the sea salt treatment and control groups. The sections of buccal mucosa cancer tissue showed that canceration in the purple bamboo salt group was weaker compared with that in the sea salt group. Similar results were observed in the lesion section of the cervical lymph. Using reverse transcription-polymerase chain reaction (RT-PCR) and western blotting, the purple bamboo salt group demonstrated an increase in Bcl-2-associated X protein (Bax) and a decrease in B cell lymphoma-2 (Bcl-2), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, compared with the sea salt and control groups. The results demonstrated that purple bamboo salt had improved in vivo buccal mucosa cancer preventive activity compared with sea salt in mice.

  15. Quantum Chemical Study of the Solvent Effect on the Anticancer Active Molecule of Iproplatin: Structural, Electronic, and Spectroscopic Properties (IR, 1H NMR, UV)

    Science.gov (United States)

    Sadeghi, N.; Ghiasi, R.; Fazaeli, R.; Jamehbozorgi, S.

    2017-01-01

    The structural, electronic, and spectroscopic properties of the anticancer active molecule of iproplatin were investigated in the gas and liquid phases. Based on the polarizable continuum model (PCM), the solvent effect on the structural parameters, frontier orbitals, and spectroscopic parameters of the complex was investigated. The results indicate that the polarity of solvents plays a significant role in the structure and pro perties of the complex. 1H and 13C NMR chemical shifts were calculated using the Gauge-invariant atomic orbital (GIAO) method. Pt-Cl and Pt-OH bonds were investigated through a vibrational analysis. Moreover, time dependent density functional theory (TD-DFT) was used to calculate the energy, oscillatory strength, and wavelength absorption maximum (λmax) of electronic transitions and its nature within the complex.

  16. Engineer Novel Anticancer Bioagents

    Science.gov (United States)

    2010-10-01

    selection (hence to create marker-free genetically modified organism – GMO as required by FDA regulations) have failed. The overall transformation...free genetically modified organism – GMO , as required by FDA regulations). Key Research Status 1. Reconstitution of a complete FK228 biosynthetic...5 Food and Drug Administration (FDA) as a new class of anticancer drug for the treatment of 1 cutaneous T-cell lymphoma (CTCL) (1). FK228

  17. Molecular Mechanism of Enhanced Anticancer Effect of Nanoparticle Formulated LY2835219 via p16-CDK4/6-pRb Pathway in Colorectal Carcinoma Cell Line

    Directory of Open Access Journals (Sweden)

    Xu Tang

    2016-01-01

    Full Text Available LY2835219 is a dual inhibitor to CDK4 and CDK6. This study was to prepare LY2835219-loaded chitosan nanoparticles (CNP/LY and LY2835219-loaded hyaluronic acid-conjugated chitosan nanoparticles (HACNP/LY and revealed their anticancer effect and influence on p16-CDK4/6-pRb pathway against colon cell line. The nanoparticle sizes of CNP/LY and HACNP/LY were approximately 195±39.6 nm and 217±31.1 nm, respectively. The zeta potentials of CNP/LY and HACNP/LY were 37.3±1.5 mV and 30.3±2.2 mV, respectively. And the preparation process showed considerable drug encapsulation efficiency and loading efficiency. LY2835219, CNP/LY, and HACNP/LY inhibited HT29 cell proliferation with 0.68, 0.54, and 0.30 μM of IC50, respectively. G1 phase was arrested by LY2835219 and its formulations. Furthermore, inhibition of CDK4/6 by LY2835219 formulations induced CDK4, CDK6, cyclin D1, and pRb decrease and p16 increase at both protein and mRNA levels. Overall, nanoparticle formulated LY2835219 could enhance the cytotoxicity and cell cycle arrest, and HACNP/LY strengthened the trend furtherly compared to CNP/LY. It is the first time to demonstrate the anticancer effect and mechanism against HT29 by LY2835219 and its nanoparticles. The drug and its nanoparticle formulations delay the cell growth and arrest cell cycle through p16-CDK4/6-pRb pathway, while the nanoparticle formulated LY2835219 could strengthen the process.

  18. 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.

  19. β-Catenin Mediates Anti-adipogenic and Anticancer Effects of Arctigenin in Preadipocytes and Breast Cancer Cells.

    Science.gov (United States)

    Lee, Jihye; Imm, Jee-Young; Lee, Seong-Ho

    2017-03-15

    Arctigenin is a lignan abundant in Asteraceae plants and has anti-inflammatory, antiobesity, and anticancer activities. Obesity is one of the leading causes of several types of cancers including breast cancer. The current study was performed to investigate if arctigenin suppresses differentiation of preadipocytes and proliferation of breast cancer cells and to explore potential molecular mechanisms. Treatment of arctigenin reduced lipid accumulation in differentiated 3T3-L1 adipocytes in a dose- and time-dependent manner without toxicity. Arctigenin suppressed the expression of peroxisome proliferator-activated receptor-gamma (PPARγ), CCAAT/enhancer-binding protein-alpha (C/EBPα), perilipin, and fatty acid binding protein 4 (FABP4) in a dose-dependent manner in differentiated 3T3-L1 cells. Both total and unphosphorylated (active) β-catenin were increased in whole cell lysates and the nuclear fraction of differentiated 3T3-L1 cells treated with 25 μM arctigenin. On the other hand, arctigenin decreased proliferation of two human breast cancer cells (MCF-7 and MDA-MB-231). Arctigenin induced apoptosis and decreased expression of total and unphosphorylated (active) β-catenin and cyclin D1 in MCF-7, but not in MDA-MB-231. These data indicate that arctigenin suppressed adipogenesis in preadipocytes and activated apoptosis in estrogen receptor (ER) positive breast cancer cells through modulating expression of β-catenin.

  20. Anticancer and Anti-Inflammatory Properties of Ganoderma lucidum Extract Effects on Melanoma and Triple-Negative Breast Cancer Treatment

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    Antonio Barbieri

    2017-02-01

    Full Text Available Among the most important traditional medicinal fungi, Ganoderma lucidum has been used as a therapeutic agent for the treatment of numerous diseases, including cancer, in Oriental countries. The aim of this study is to investigate the anti-inflammatory, anticancer and anti-metastatic activities of Ganoderma lucidum extracts in melanoma and triple-negative breast cancer cells. Ganoderma lucidum extracts were prepared by using common organic solvents; MDA-MB 231 and B16-F10 cell lines were adopted as cellular models for triple-negative breast cancer and melanoma and characterized for cell viability, wound-healing assay and measurement of cytokines secreted by cancer cells under pro-inflammatory conditions (incubation with lipopolysaccharide, LPS and pretreatment with Ganoderma lucidum extract at different concentrations. Our study demonstrates, for the first time, how Ganoderma lucidum extracts can significantly inhibit the release of IL-8, IL-6, MMP-2 and MMP-9 in cancer cells under pro-inflammatory condition. Interestingly, Ganoderma lucidum extracts significantly also decrease the viability of both cancer cells in a time- and concentration-dependent manner, with abilities to reduce cell migration over time, which is correlated with a lower release of matrix metalloproteases. Taken together, these results indicate the possible use of Ganoderma lucidum extract for the therapeutic management of melanoma and human triple-negative breast cancer.

  1. Low-temperature affected LC-PUFA conversion and associated gene transcript level in Nannochloropsis oculata CS-179

    Science.gov (United States)

    Ma, Xiaolei; Zhang, Lin; Zhu, Baohua; Pan, Kehou; Li, Si; Yang, Guanpin

    2011-09-01

    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 × 106 cell mL-1, the highest growth was observed at 25°C 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°C. Real-time PCR showed that the abundance of Δ6-desaturase gene transcripts was significantly different among 5 culture temperatures and the highest transcript level (15°C) 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°C), and the highest transcript level (20°C) of Nanoc-E took off at cycle 21.18. The highest conversion rate (39.3%) of Δ6-desaturase was also gained at 20°C. 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, Δ6-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.

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

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    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.

  3. Docetaxel-Loaded Self-Assembly Stearic Acid-Modified Bletilla striata Polysaccharide Micelles and Their Anticancer Effect: Preparation, Characterization, Cellular Uptake and In Vitro Evaluation

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    Qingxiang Guan

    2016-12-01

    Full Text Available Poorly soluble drugs have low bioavailability after oral administration, thereby hindering effective drug delivery. A novel drug-delivery system of docetaxel (DTX-based stearic acid (SA-modified Bletilla striata polysaccharides (BSPs copolymers was successfully developed. Particle size, zeta potential, encapsulation efficiency (EE, and loading capacity (LC were determined. The DTX release percentage in vitro was determined using high performance liquid chromatography (HPLC. The hemolysis and in vitro anticancer activity were studied. Cellular uptake and apoptotic rate were measured using flow cytometry assay. Particle size, zeta potential, EE and LC were 125.30 ± 1.89 nm, −26.92 ± 0.18 mV, 86.6% ± 0.17%, and 14.8% ± 0.13%, respectively. The anticancer activities of DTX-SA-BSPs copolymer micelles against HepG2, HeLa, SW480, and MCF-7 (83.7% ± 1.0%, 54.5% ± 4.2%, 48.5% ± 4.2%, and 59.8% ± 1.4%, respectively were superior to that of docetaxel injection (39.2% ± 1.1%, 44.5% ± 5.3%, 38.5% ± 5.4%, and 49.8% ± 2.9%, respectively at 0.5 μg/mL drug concentration. The DTX release percentage of DTX-SA-BSPs copolymer micelles and docetaxel injection were 66.93% ± 1.79% and 97.06% ± 1.56% in two days, respectively. Cellular uptake of DTX-FITC-SA-BSPs copolymer micelles in cells had a time-dependent relation. Apoptotic rate of DTX-SA-BSPs copolymer micelles and docetaxel injection were 73.48% and 69.64%, respectively. The SA-BSPs copolymer showed good hemocompatibility. Therefore, SA-BSPs copolymer can be used as a carrier for delivering hydrophobic drugs.

  4. Docetaxel-Loaded Self-Assembly Stearic Acid-Modified Bletilla striata Polysaccharide Micelles and Their Anticancer Effect: Preparation, Characterization, Cellular Uptake and In Vitro Evaluation.

    Science.gov (United States)

    Guan, Qingxiang; Sun, Dandan; Zhang, Guangyuan; Sun, Cheng; Wang, Miao; Ji, Danyang; Yang, Wei

    2016-12-02

    Poorly soluble drugs have low bioavailability after oral administration, thereby hindering effective drug delivery. A novel drug-delivery system of docetaxel (DTX)-based stearic acid (SA)-modified Bletilla striata polysaccharides (BSPs) copolymers was successfully developed. Particle size, zeta potential, encapsulation efficiency (EE), and loading capacity (LC) were determined. The DTX release percentage in vitro was determined using high performance liquid chromatography (HPLC). The hemolysis and in vitro anticancer activity were studied. Cellular uptake and apoptotic rate were measured using flow cytometry assay. Particle size, zeta potential, EE and LC were 125.30 ± 1.89 nm, -26.92 ± 0.18 mV, 86.6% ± 0.17%, and 14.8% ± 0.13%, respectively. The anticancer activities of DTX-SA-BSPs copolymer micelles against HepG2, HeLa, SW480, and MCF-7 (83.7% ± 1.0%, 54.5% ± 4.2%, 48.5% ± 4.2%, and 59.8% ± 1.4%, respectively) were superior to that of docetaxel injection (39.2% ± 1.1%, 44.5% ± 5.3%, 38.5% ± 5.4%, and 49.8% ± 2.9%, respectively) at 0.5 μg/mL drug concentration. The DTX release percentage of DTX-SA-BSPs copolymer micelles and docetaxel injection were 66.93% ± 1.79% and 97.06% ± 1.56% in two days, respectively. Cellular uptake of DTX-FITC-SA-BSPs copolymer micelles in cells had a time-dependent relation. Apoptotic rate of DTX-SA-BSPs copolymer micelles and docetaxel injection were 73.48% and 69.64%, respectively. The SA-BSPs copolymer showed good hemocompatibility. Therefore, SA-BSPs copolymer can be used as a carrier for delivering hydrophobic drugs.

  5. Eriodictyol-induced anti-cancer and apoptotic effects in human hepatocellular carcinoma cells are associated with cell cycle arrest and modulation of apoptosis-related proteins

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    Fang Wang

    2016-06-01

    Full Text Available The objective of the present study was to investigate the anti-cancer effects of eriodictyol in human hepatocellular carcinoma cells (Hep-G2 and normal liver hepatocyte cell line (AML12 along with evaluating its mode of action. Sulforhodamine B assay was used to evaluate the cytotoxic effect of the compound while as fluorescence microscopy was involved to demonstrate the effect of eriodictyol on cellular apoptosis. Flow cytometry was used to investigate the effect of eriodictyol on cell cycle while Western blot analysis revealed the effect on apoptosis-related protein expressions. Results indicate that eriodictyol-induced selective and concentration-dependent cytotoxic effect on Hep-G2 cancer cells while AML12 normal liver cells were very less susceptible to its effect. Eriodictyol-induced apoptosis related morphological changes including chromatin condensation and nuclear fragmentation. It also induced G2/M cell cycle arrest in these cells. Eriodictyol led to up-regulation of Bax and PARP and down-regulation of Bcl-2 protein.

  6. Pu-erh tea has in vitro anticancer activity in TCA8113 cells and preventive effects on buccal mucosa cancer in U14 cells injected mice in vivo.

    Science.gov (United States)

    Zhao, Xin; Qian, Yu; Zhou, Ya-Lin; Wang, Rui; Wang, Qiang; Li, Gui-Jie

    2014-01-01

    Pu-erh tea is a functional tea production in China. The functional effects should be proved. The oral cancer preventive and antimetastatic effects of Pu-erh tea in vitro and in vivo have been studied respectively. Pu-erh tea showed an inhibitory effect on human tongue carcinoma TCA8113 cells proliferation tested by 3-(4,5-Dimethyl-2-Thiazolyl)-2,5-Diphenyltetrazolium Bromide assay and induced TCA8113 apoptosis shown anticancer effect. The antimetastatic effect of Pu-erh tea in TCA8113 cells was proved by the decreasing of matrix metalloproteinases (MMPs) and increasing of tissue inhibitors of metalloproteinases (TIMPs) mRNA transcription. In the animal experiments, the tumor volumes and lymph node metastasis rates of Pu-erh tea-treated mice were smaller than control mice. Pu-erh tea reduced the levels of the serum proinflammatory cytokines interleukin (IL)-6, IL-12, tumor necrosis factor-α, and interferon-γ to a greater extent compared with the control mice, and the levels of 200 μg/mL treatment was more close to the normal mice than 100 μg/mL treated mice. Pu-erh tea also significantly induced apoptosis in tissues of mice (P Pu-erh tea has cancer preventive and anti-metastatic effects on buccal mucosa cancer, the higher concentration get better efficiency.

  7. 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.

  8. 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.

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    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.

  9. 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

  10. 1-aminocyclopropane-1-carboxylic acid (ACC)-induced reorientation of cortical microtubules is accompanied by a transient increase in the transcript levels of gamma-tubulin complex and katanin genes in azuki bean epicotyls.

    Science.gov (United States)

    Soga, Kouichi; Yamaguchi, Aya; Kotake, Toshihisa; Wakabayashi, Kazuyuki; Hoson, Takayuki

    2010-09-15

    The effects of 1-aminocyclopropane-1-carboxylic acid (ACC), the immediate precursor of ethylene, on growth, orientation of cortical microtubules, and the transcript levels of gamma-tubulin complex (VaTUG and VaGCP3) and katanin (VaKTN1) genes in azuki bean (Vigna angularis) epicotyls were examined. ACC inhibited elongation growth and stimulated lateral growth of epicotyls dose dependently. It also reduced the percentage of cells with transverse microtubules and increased the percentage of cells with longitudinal microtubules. A significant change in elongation and lateral growth was detected within 1 and 1.5 h after the start of 10(-5) M ACC treatment, respectively. On the other hand, the reorientation of cortical microtubules from transverse to longitudinal direction began within 0.5 h, and continued until 2 h after the start of ACC treatment. ACC at 10(-5) M increased the transcript level of VaTUG, VaGCP3 and VaKTN1 within 0.5 h, and the levels of VaTUG and VaGCP3 became maximum at 1h and that of VaKTN1 at 1.5 h, followed by a decrease to the control level. These results suggest that ACC transiently increases the transcript levels of gamma-tubulin complex and katanin genes, which may facilitate reorientation of cortical microtubules and modification of growth anisotropy from elongation to lateral growth in azuki bean epicotyls.

  11. 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.

  12. Mitochondrial DNA transcription levels during spermatogenesis and early development in doubly uniparental inheritance of the mitochondrial DNA system of the blue mussel Mytilus galloprovincialis.

    Science.gov (United States)

    Sano, Natsumi; Obata, Mayu; Komaru, Akira

    2013-08-01

    In some species of bivalve, there are two highly diverged mitochondrial genomes, one found in all individuals (F type) and the other normally in males only (M type). In Mytilus, a maternally-dependent sex ratio of the progeny has been reported. Some females almost exclusively produce daughters, while others produce a high proportion of sons. We previously reported that in M. galloprovincialis, M type mtDNA copy number may be maintained during spermatogenesis and the development of larvae of male-biased mothers to sustain the doubly uniparental inheritance system. In this study, we investigated transcription levels of M type mtDNA before and after fertilization to understand its function in the germ line. First, we quantified transcription levels of M type mtDNA in testicular cells dissected using laser-capture micro-dissection. The transcription levels of M type mtDNA were not significantly different between spermatogonia and spermatocytes versus spermatids and spermatozoa. Next, we examined differences in transcription levels of M type mtDNA between larvae from male-biased and female-biased mothers. The transcription levels of M type mtDNA significantly increased 24 and 48 h after fertilization in male-biased crosses. By contrast, transcription levels significantly decreased in female-biased crosses. These results suggest M type mtDNA may play a role in early germ line formation.

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

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    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.

  14. 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.

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

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    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.

  16. 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

  17. The anticancer activity of propolis

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    Jacek Nikliński

    2012-04-01

    Full Text Available Propolis and its compounds have been the subject of many studies due to their antimicrobial and antiinflammatory activity; however, it is now known that they also possess antitumor properties. This review aims to summarize the results of studies on the mechanism of activity of propolis and its active compounds such as CAPE and chrysin in the apoptotic process, and their influence on the proliferation of cancer cells. Our review shows that propolis and its presented compounds induce apoptosis pathways in cancer cells. The antiproliferative effects of propolis, CAPE or chrysin in cancer cells are the result of the suppression of complexes of cyclins, as well as cell cycle arrest. The results of in vitro and in vivo studies suggest that propolis, CAPE and chrysin may inhibit tumor cell progression and may be useful as potential chemotherapeutic or chemopreventive anticancer drugs.

  18. [Anticancer propaganda: myth or reality?].

    Science.gov (United States)

    Demin, E V; Merabishvili, V M

    2014-01-01

    The authors raise a very important problem of anticancer propaganda aimed at the early detection of cancer to be solved nowadays by means of screening and constructive interaction between oncologists and the public. To increase the level of knowledge of the population in this area it is necessary to expand the range of its adequate awareness of tumor diseases. Only joint efforts can limit the destructive effect of cancer on people's minds, so that every person would be responsible for his own health, clearly understanding the advantages of early visit to a doctor. This once again highlights the need of educational work with the public, motivational nature of which allows strengthening the value of screening in the whole complex of measures to fight cancer.

  19. Bacteriocins as potential anticancer agents

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    Sukhraj eKaur

    2015-11-01

    Full Text Available 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 therapeutic potential of bacteriocins against various types of cancer cell lines. Bacteriocins are ribosomally-synthesized cationic peptides secreted by almost all groups of bacteria. Some bacteriocins have shown selective cytotoxicity towards cancer cells as compared to normal cells. This makes them promising candidates for further investigation and clinical trials. In this review article, we present the overview of the various cancer cell-specific cytotoxic bacteriocins, their mode of action and efficacies.

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

    Directory of Open Access Journals (Sweden)

    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

  1. Study on the Regulation of Bcl-2 Gene on Rat Spermatogenic Cells Apoptosis in Transcription Level

    Institute of Scientific and Technical Information of China (English)

    董强; 杨宇如; 黄明孔; 李虹; 张卫东; 徐震波

    2000-01-01

    Objective To detect the change of Bcl-2 gene expression in the apopototic process of spermatogenic cells in rat with vasoligation and vasostomy, and to find out the relationship between the transcription of Bcl-2 and the apoptosis of spermatognic cells.Materials & Methods Sixty adult male Sprague-Dawley rats in 3 groups were operated with vasoligation and vasostomy. Then hybridization in situ with hypersensitive Bcl-2 RNA probe was used to detect the change of Bcl-2 mRNA.Results The transcription of Bcl-2 gene in spermatogenic cells was obviously inhibited in the vasoligation group compared with that in the control group (P<0. 05), and the transcription in the vasostomy group showed no difference from that of the control group.Conclusion Bcl-2 gene has an anti-apoptotic effect in rats with vasostomy, and there was a transcriptional regulation of Bcl-2 gene in rat spermatogenic cell during the period of pre-vasoligation to post-vasoligation and to post-vasosotomy.

  2. Cell death signaling and anticancer therapy

    Directory of Open Access Journals (Sweden)

    Lorenzo eGalluzzi

    2011-05-01

    Full Text Available For a long time, it was commonly believed that efficient anticancer regimens would either trigger the apoptotic demise of tumor cells or induce a permanent arrest in the G1 phase of the cell cycle, i.e., senescence. The recent discovery that necrosis can occur in a regulated fashion and the increasingly more precise characterization of the underlying molecular mechanisms have raised great interest, as non-apoptotic pathways might be instrumental to circumvent the resistance of cancer cells to conventional, pro-apoptotic therapeutic regimens. Moreover, it has been shown that some anticancer regimens engage lethal signaling cascades that can ignite multiple oncosuppressive mechanisms, including apoptosis, necrosis and senescence. Among these signaling pathways is mitotic catastrophe, whose role as a bona fide cell death mechanism has recently been reconsidered. Thus, anticancer regimens get ever more sophisticated, and often distinct strategies are combined to maximize efficacy and minimize side effects. In this review, we will discuss the importance of apoptosis, necrosis and mitotic catastrophe in the response of tumor cells to the most common clinically employed and experimental anticancer agents.

  3. High ACSL5 Transcript Levels Associate with Systemic Lupus Erythematosus and Apoptosis in Jurkat T Lymphocytes and Peripheral Blood Cells

    Science.gov (United States)

    2011-01-01

    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. PMID:22163040

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

    Directory of Open Access Journals (Sweden)

    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.

  5. 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.

  6. Wnt signaling regulates the stemness of lung cancer stem cells and its inhibitors exert anticancer effect on lung cancer SPC-A1 cells.

    Science.gov (United States)

    Zhang, Xueyan; Lou, Yuqing; Wang, Huimin; Zheng, Xiaoxuan; Dong, Qianggang; Sun, Jiayuan; Han, Baohui

    2015-04-01

    Wnt signaling plays an important role in regulating the activity of cancer stem cells (CSCs) in a variety of cancers. In this study, we explored the role of Wnt signaling in the lung cancer stem cells (LCSCs). LCSCs were obtained by sphere culture, for which human lung adenocarcinoma cell line SPC-A1 was treated with IGF, EGF and FGF-10. The stemness of LCSCs was confirmed by immunofluorescence, and pathway analysis was performed by functional genome screening and RT-PCR. The relationship between the identified signaling pathway and the expression of the stemness genes was explored by agonist/antagonist assay. Moreover, the effects of different signaling molecule inhibitors on sphere formation, cell viability and colony formation were also analyzed. The results showed that LCSCs were successfully generated as they expressed pluripotent stem cell markers Nanog and Oct 4, and lung distal epithelial markers CCSP and SP-C, by which the phenotype characterization of stem cells can be confirmed. The involvement of Wnt pathway in LCSCs was identified by functional genome screening and verified by RT-PCR. The expression of Wnt signaling components was closely related to the expression of the Nanog and Oct 4. Furthermore, targeting Wnt signaling pathway by using different signaling molecule inhibitors can exert anticancer effects. In conclusion, Wnt signaling pathway is involved in the stemness regulation of LCSCs and might be considered as a potential therapeutic target in lung adenocarcinoma.

  7. 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.

  8. Investigation of anticancer effect of Xanthoceraside in vitro and the mechanism of Xanthoceraside-induced human breast cancer MCF-7 cell death

    Institute of Scientific and Technical Information of China (English)

    JI Xue-fei; XIA Ming-yu; CHI Tian-yan; WANG Li-hua; YANG Bai-zhen; ZOU Li-bo

    2008-01-01

    Objective To investigate the anticancer effect of xanthoceraside in vitro and the possible mechanisms involved in the potent antiproliferative effect on human breast cancer MCF-7 cell. Methods The inhibition rate of different tumor cells and human peripheral blood lymphocyte cells was investigated by MTT assay. AO/EB double fluorescent dye staining was used to investigate the morphology changes of MCF-7. The DNA agarose gel electrophoresis was further used to observe the DNA Fragmentation. Flow eytometry was employed to investigate the volume changes, the cell cycle distribution and the mitoehondrial membrane potential of MCF-7. The antioxidant N-acetylcysteine (NAC) was chosen to detect the influence on oxidantstress system of MCF-7 cells. Necrostatin-1 was next chosen to detect the influence on antiproliferative effect of xanthoceraside-treated MCF-7 cells. Results Xanthoceraside could inhibit the proliferation of tumor cells significantly in a dose-dependent manner and it has no eytotoxie effects on human peripheral blood lymphocyte cells in vitro. Cytoplasm vacuole was observed but no significant condense of nuclear ehromatin was found, meanwhile, MCF-7 cells were bigger and smear was observed by agarose gel electrophoresis after MCF-7 cells were exposed to xanthoceraside. The cell cycle distribution of MCF-7 was greatly changed after exposure to xanthoceraside with an obvious G1 arrest. The mitochondrial membrane potential showed significant decrease. NAC attenuate the antiproliferative effect of xanthoceraside-treated MCF-7 cells but necrostatin-1 had no effects. Conclnsions Xanthoceraside-indueed necrosis might be dependent of mitochondria, meanwhile reactive oxygen species (ROS) participated in it. The xanthoceraside-indueed MCF-7 cell death might not be the cell necrosis which initiated by Fas/TNFR and must be through RIP1 kinase.

  9. Anti-cancer effects of novel flavonoid vicenin-2 as a single agent and in synergistic combination with docetaxel in prostate cancer.

    Science.gov (United States)

    Nagaprashantha, Lokesh Dalasanur; Vatsyayan, Rit; Singhal, Jyotsana; Fast, Spence; Roby, Rhonda; Awasthi, Sanjay; Singhal, Sharad S

    2011-11-01

    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 with decreasing c-Myc, cyclin D1, cyclin B1, CDK4, PCNA and hTERT in vitro. VCN-2 reached a level of 2.6±0.3μmol/l in serum after oral administration in mice which reflected that VCN-2 is orally absorbed. The i.v. administration of docetaxel (DTL), current drug of choice in androgen-independent CaP, is associated with dose-limiting toxicities like febrile neutropenia which has lead to characterization of alternate routes of administration and potential combinatorial regimens. In this regard, VCN-2 in combination with DTL synergistically inhibited the growth of prostate tumors in vivo with a greater decrease in the levels of AR, pIGF1R, pAkt, PCNA, cyclin D1, Ki67, CD31, and increase in E-cadherin. VCN-2 has been investigated for radioprotection and anti-inflammatory properties. This is the first study on the anti-cancer effects of VCN-2. In conclusion, our investigations collectively provide strong evidence that VCN-2 is effective against CaP progression along with indicating that VCN-2 and DTL co-administration is more effective than either of the single agents in androgen-independent prostate cancer.

  10. Efeito da adição de precursores na produção de alcaloide anticancerígeno usando a técnica de planejamento experimental Effect of the precursor addition on the anticancer alkaloid production using experimental design methodology

    Directory of Open Access Journals (Sweden)

    Oselys Rodriguez Justo

    2009-01-01

    Full Text Available The effect of precursors on the anticancer alkaloid production by submerged fermentation using M. anisopliae 3935 was studied, according to complete experimental design 2² with three central points. The results showed that lysine was the most important variable, however, when both lysine and glucose were added to the fermentation medium, the alkaloid production reached, approximately, 17 mg L-1 after 120 hours of fermentation. Then, the scale-up of the process was carried out and these results were confirmed. Finally, 35 mg L-1 of alkaloid at 192 h were attained after increment of added aminoacid lysine.

  11. Recent progress on anti-cancer effect of cardiac glycosides%强心苷类抗癌作用研究进展

    Institute of Scientific and Technical Information of China (English)

    陈大朋; 唐泽耀; 熊永建; 林原

    2011-01-01

    Cardiac glycosides include exogenous cardiac glyco-sides and endogenous cardiac glycosides. This article focuses on anti-cancer mechanism of cardiac glycosides, including the inhibition of Na , K + -ATPase activity, of hypoxia inducible factor -1, of fibroblast growth factor, nuclear factor and of the activity of topoisomerase, blockade of estrogen receptors, induction of ap-optosis and cytotoxicity. The effects of cardiac glycosides onbreast cancer, prostate cancer, and other cancers and the possible relationship between endogenous cardiac glycosides and cancer are also discussed.%强心苷类物质可分为外源性强心苷类和内源性强心苷类.该文主要阐述了强心苷类的抗癌作用机制与其抑制Na+,K+-ATP酶、缺氧诱导因子-1、成纤维细胞生长因子、核转录因子及拓扑异构酶的活性,阻断雌激素受体,诱导细胞凋亡以及细胞毒作用相关;简要阐述了强心苷类对乳腺癌及前列腺癌等恶性肿瘤的作用效果以及内源性强心苷类与癌症的可能关系.

  12. Mechanisms of action of DNA-damaging anticancer drugs in treatment of carcinomas: is acute apoptosis an "off-target" effect?

    Science.gov (United States)

    Havelka, Aleksandra Mandic; Berndtsson, Maria; Olofsson, Maria Hägg; Shoshan, Maria C; Linder, Stig

    2007-10-01

    DNA damage induces apoptosis of cells of hematological origin. Apoptosis is also widely believed to be the major antiproliferative mechanism of DNA damaging anticancer drugs in other cell types, and a large number of laboratories have studied drug-induced acute apoptosis (within 24 hours) of carcinoma cells. It is, however, often overlooked that induction of apoptosis of carcinoma cells generally requires drug concentrations that are at least one order of magnitude higher than those required for loss of clonogenicity. This is true for different DNA damaging drugs such as cisplatin, doxorubicin and camptothecin. We here discuss apoptosis induction by DNA damaging agents using cisplatin as an example. Recent studies have shown that cisplatin induces caspase activation in enucleated cells (cytoplasts lacking a cell nucleus). Cisplatin-induced apoptosis in both cells and cytoplasts is associated with rapid induction of cellular reactive oxygen species and increases in [Ca(2+)](i). Cisplatin has also been reported to induce clustering of Fas/CD95 in the plasma membrane. Available data suggest that the primary responses to cisplatin-induced DNA damage are induction of long-term growth arrest ("premature cell senescence") and mitotic catastrophe, whereas acute apoptosis may be due to "off-target effects" not necessarily involving DNA damage.

  13. Structure Effect of Some New Anticancer Pt(II) Complexes of Amino Acid Derivatives with Small Branched or Linear Hydrocarbon Chains on Their DNA Interaction.

    Science.gov (United States)

    Kantoury, Mahshid; Eslami Moghadam, Mahboube; Tarlani, Ali Akbar; Divsalar, Adeleh

    2016-07-01

    The aim of this study was to investigate the structure effect and identify the modes of binding of amino acid-Pt complexes to DNA molecule for cancer treatment. Hence, three novel water soluble platinum complexes, [Pt(phen)(R-gly)]NO3 (where phen is 1,10-phenanthroline, R-gly is methyl, amyl, and isopentyl-glycine), have been synthesized and characterized by spectroscopic methods, conductivity measurements, and chemical analysis. The anticancer activities of synthesized complexes were investigated against human breast cancer cell line of MDA-MB 231. The 50% cytotoxic concentration values were determined to be 42.5, 58, and 70 μm for methyl-, amyl-, and isopentyl-gly complexes, respectively. These complexes were interacted with calf thymus DNA (ct-DNA) via positive cooperative interaction. The modes of binding of the complexes to DNA were investigated by fluorescence spectroscopy and circular dichroism in combination with a molecular docking study. The result indicates that complexes with small or branched hydrocarbon chains can intercalate with DNA. This is while amyl complexes with linear chains interacted additionally via groove binding. The results of the negative value of Gibbs energy for binding of isopentyl-platinum to DNA and those of the molecular docking were coherent. Furthermore, the docking results demonstrated that hydrophobic interaction plays an important role in the complex-DNA interaction.

  14. 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.

  15. Effects of Net Charge on Biological Activities of Alpha-helical Anticancer Peptides%净电荷对螺旋型抗癌肽生物活性的影响

    Institute of Scientific and Technical Information of China (English)

    黄宜兵; 翟乃翠; 高贵; 陈育新

    2012-01-01

    以高活性两亲性α-螺旋型阳离子抗癌肽A12L/A20L(多肽P)为模板,在其亲水面进行氨基酸定点取代,获得了一系列带有不同净电荷的多肽类似物,研究了净电荷对螺旋型抗癌肽生物活性的影响.结果表明,抗癌肽净电荷的改变对其溶血活性影响较小(最大差异为2倍),而对抗癌活性和选择性的影响显著(最大差异为10倍).抗癌肽P的净电荷最适范围为+7到+8,分子间静电排斥作用的最佳数目为3~5个,高于或低于此范围,其抗癌活性和选择性均明显降低.与人的正常细胞相比,负电性的癌细胞膜对于抗癌肽的净电荷变化更敏感,表明两亲性螺旋型抗癌肽针对癌细胞与正常细胞表现出良好的选择特异性.%Owing to the low possibility of induction of resistance, amphipathic a-helical anticancer peptides whose sole target is the biomembrane show their promising potentials in cancer treatments. Obtained in the previous study, an amphipathic a-helical anticancer peptide A12I/A20L( Peptide P) with significant anticancer activity was utilized as the framework to systematically design a series of peptide analogs with different net charges by amino acid substitutions on the polar face, and to study the effects of net charge on biological activities of cationic anticancer peptides. The results showed that there was an obvious net charge threshold among peptide analogs, that was the net charge of +7 to +8 and the number of electrostatic repulsion of 3-5. Increases or decreases of net charges beyond the threshold value resulted in a dramatic reduction in both anticancer activity and therapeutic index. The alteration on net charges of peptides exhibited weak effect on hemo-lytic activity(maximum 2-fold) but significant influence on anticancer activity and therapeutic index( maximum 10-fold) , respectively. Compared with the neutral membrane of human normal cells, the negatively charged membrane of cancer cells was much more

  16. Improved Anticancer Photothermal Therapy Using the Bystander Effect Enhanced by Antiarrhythmic Peptide Conjugated Dopamine-Modified Reduced Graphene Oxide Nanocomposite.

    Science.gov (United States)

    Yu, Jiantao; Lin, Yu-Hsin; Yang, Lingyan; Huang, Chih-Ching; Chen, Liliang; Wang, Wen-Cheng; Chen, Guan-Wen; Yan, Junyan; Sawettanun, Saranta; Lin, Chia-Hua

    2017-01-01

    Despite tremendous efforts toward developing novel near-infrared (NIR)-absorbing nanomaterials, improvement in therapeutic efficiency remains a formidable challenge in photothermal cancer therapy. This study aims to synthesize a specific peptide conjugated polydopamine-modified reduced graphene oxide (pDA/rGO) nanocomposite that promotes the bystander effect to facilitate cancer treatment using NIR-activated photothermal therapy. To prepare a nanoplatform capable of promoting the bystander effect in cancer cells, we immobilized antiarrhythmic peptide 10 (AAP10) on the surface of dopamine-modified rGO (AAP10-pDA/rGO). Our AAP10-pDA/rGO could promote the bystander effect by increasing the expression of connexin 43 protein in MCF-7 breast-cancer cells. Because of its tremendous ability to absorb NIR absorption, AAP10-pDA/rGO offers a high photothermal effect under NIR irradiation. This leads to a massive death of MCF-7 cells via the bystander effect. Using tumor-bearing mice as the model, it is found that NIR radiation effectively ablates breast tumor in the presence of AAP10-pDA/rGO and inhibits tumor growth by ≈100%. Therefore, this research integrates the bystander and photothermal effects into a single nanoplatform in order to facilitate an efficient photothermal therapy. Furthermore, our AAP10-pDA/rGO, which exhibits both hyperthermia and the bystander effect, can prevent breast-cancer recurrence and, therefore, has great potential for future clinical and research applications.

  17. The influence of the BRAF V600E mutation in thyroid cancer cell lines on the anticancer effects of 5-aminoimidazole-4-carboxamide-ribonucleoside.

    Science.gov (United States)

    Choi, Hyun-Jeung; Kim, Tae Yong; Chung, Namhyun; Yim, Ji Hye; Kim, Won Gu; Kim, Jin A; Kim, Won Bae; Shong, Young Kee

    2011-10-01

    5-Aminoimidazole-4-carboxamide-ribonucleoside (AICAR) is an activator of 5'-AMP-activated protein kinase (AMPK), which plays a role in the maintenance of cellular energy homeostasis. Activated AMPK inhibits the protein kinase mechanistic target of rapamycin, thereby reducing the extent of protein translation and suppressing both cell growth and cell cycle entry. Recent reports indicate that AMPK-mediated growth inhibition is achieved via an action of the RAF-MEK-ERK mitogen-activated protein kinase pathway in melanoma cells harboring the V600E mutant form of the BRAF oncogene. In this study, we investigated the anti-cancer efficacy of AICAR by measuring its effects on proliferation, apoptosis, and cell cycle progression of BRAF wild-type and V600E-mutant thyroid cancer cell lines. We also explored the mechanism underlying these effects. AICAR inhibited the proliferation of BRAF V600E-mutant thyroid cancer cell lines more strongly than was the case with wild-type cell lines. The suppressive effect of AICAR on cell proliferation was associated with increased S-phase cell cycle arrest and apoptosis. Interestingly, AICAR suppressed phosphorylation of ERK and p70S6K in BRAF V600E-mutant thyroid cancer cells, but rather increased phosphorylation in wild-type cells. Together, the results indicate that AICAR-induced AMPK activation in BRAF V600E-mutant thyroid cancer cell lines resulted in increases in apoptosis and S-phase arrest via downregulation of ERK and p70S6K activity. Thus, regulation of AMPK activity may be potentially useful as a therapy for thyroid cancer if the cancer harbors a BRAF V600E mutation.

  18. 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.

  19. Distinct regulatory mechanisms of the human ferritin gene by hypoxia and hypoxia mimetic cobalt chloride at the transcriptional and post-transcriptional levels.

    Science.gov (United States)

    Huang, Bo-Wen; Miyazawa, Masaki; Tsuji, Yoshiaki

    2014-12-01

    Cobalt chloride has been used as a hypoxia mimetic because it stabilizes hypoxia inducible factor-1α (HIF1-α) and activates gene transcription through a hypoxia responsive element (HRE). However, differences between hypoxia and hypoxia mimetic cobalt chloride in gene regulation remain elusive. Expression of ferritin, the major iron storage protein, is regulated at the transcriptional and posttranscriptional levels through DNA and RNA regulatory elements. Here we demonstrate that hypoxia and cobalt chloride regulate ferritin heavy chain (ferritin H) expression by two distinct mechanisms. Both hypoxia and cobalt chloride increased HIF1-α but a putative HRE in the human ferritin H gene was not activated. Instead, cobalt chloride but not hypoxia activated ferritin H transcription through an antioxidant responsive element (ARE), to which Nrf2 was recruited. Intriguingly, cobalt chloride downregulated ferritin H protein expression while it upregulated other ARE-regulated antioxidant genes in K562 cells. Further characterization demonstrated that cobalt chloride increased interaction between iron regulatory proteins (IRP1 and IRP2) and iron responsive element (IRE) in the 5'UTR of ferritin H mRNA, resulting in translational block of the accumulated ferritin H mRNA. In contrast, hypoxia had marginal effect on ferritin H transcription but increased its translation through decreased IRP1-IRE interaction. These results suggest that hypoxia and hypoxia mimetic cobalt chloride employ distinct regulatory mechanisms through the interplay between DNA and mRNA elements at the transcriptional and post-transcriptional levels.

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

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    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.

  1. Anticancer and antiangiogenic effects of methanol extracts of Lonicera caprifolium L. on C6 rat glioma cells

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    Nergiz Hacer Turgut

    2016-03-01

    Full Text Available Objective: Gliomas are brain tumors with high morbidity and mortality. For the treatment of gliomas, it is important to develop new and powerful treatments that could complement existing clinical treatment. Lonicera caprifolium L. (L. caprifolium has various uses in herbal traditional medicine. This study was conducted to determine the phenolic acid levels and DNA damage protection potential of L. caprifolium extract, and to explore the antitumor effect of the extract by investigating its toxicity on C6 rat glioma cell lines and normal L929 mouse fibroblast cell lines. We also aimed to investigate the antiangiogenic potential of the extract. Method: Phenolic acid content was determined by HPLC analysis. DNA damage protection potential was evaluated on pBR322 plasmid DNA. The effect of extracts on the proliferation of cancer cells was evaluated by XTT assay. Antiangiogenic effect was determined with Chorioallantoic membrane model. Results: The extract was found rich in vanillic acid (273.003 µg/g; while the amount of chlorogenic acid was almost at negligible level (0.028 µg/g. 0.005-0.05 mg / ml extract protected against the hazardous effects of UV and H2O2 in all DNA bands. The presence of the extract significantly reduced C6 cell proliferation compared to control (p<0.05. The extract had antiproliferative effect with a half maximum inhibition of concentration (IC50 value of 0.45 mg/ml. L. caprifolium extract in 10-6, 10-5 and 10-4 M concentrations caused antiangiogenic effect. Antiangiogenic scores of L. caprifolium were 0.6, 0.73 and 1.6, respectively. Conclusions: These results show that L. caprifolium has potential cytotoxic and antiangiogenic effect on C6 rat glioma cells and that the phenolic acid content of the plant may partially influence these activities.

  2. Oral delivery of anticancer drugs

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    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...

  3. Relationship between ganglioside expression and anti-cancer effects of the monoclonal antibody against epithelial cell adhesion molecule in colon cancer.

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    Kwak, Dong Hoon; Ryu, Jae-Sung; Kim, Chang-Hyun; Ko, Kisung; Ma, Jin Yeul; Hwang, Kyung-A; Choo, Young-Kug

    2011-12-31

    The human colorectal carcinoma-associated GA733 antigen epithelial cell adhesion molecule (EpCAM) was initially described as a cell surface protein selectively expressed in some myeloid cancers. Gangliosides are sialic acid-containing glycosphingolipids involved in inflammation and oncogenesis. We have demonstrated that treatment with anti-EpCAM mAb and RAW264.7 cells significant inhibited the cell growth in SW620 cancer cells, but neither anti-EpCAM mAb nor RAW264.7 cells alone induced cytotoxicity. The relationship between ganglioside expression and the anti- cancer effects of anti-EpCAM mAb and RAW264.7 was investigated by high-performance thin-layer chromatography. The results demonstrated that expression of GM1 and GD1a significantly increased in the ability of anti-EpCAM to inhibit cell growth in SW620 cells. Anti-EpCAM mAb treatment increased the expression of anti-apoptotic proteins such as Bcl-2, but the expression of pro-apoptotic proteins Bax, TNF-α, caspase-3, cleaved caspase-3, and cleaved caspase-8 were unaltered. We observed that anti-EpCAM mAb significantly inhibited the growth of colon tumors, as determined by a decrease in tumor volume and weight. The expression of anti-apoptotic protein was inhibited by treatment with anti-EpCAM mAb, whereas the expression of pro-apoptotic proteins was increased. These results suggest that GD1a and GM1 were closely related to anticancer effects of anti-EpCAM mAb. In light of these results, further clinical investigation should be conducted on anti-EpCAM mAb to determine its possible chemopreventive and/or therapeutic efficacy against human colon cancer.

  4. Rapamycin Enhances the Anti-Cancer Effect of Dasatinib by Suppressing Src/PI3K/mTOR Pathway in NSCLC Cells.

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    Bin Chen

    Full Text Available Src and the mammalian target of rapamycin (mTOR signaling are commonly activated in non-small cell lung cancer (NSCLC and hence potential targets for chemotherapy. Although the combined use of Src inhibitor Dasatinib with other chemotherapeutic agents has shown superior efficacy for cancer treatment, the mechanisms that lead to enhanced sensitivity of Dasatinib are not completely understood. In this study, we found that Rapamycin dramatically enhanced Dasatinib-induced cell growth inhibition and cell cycle G1 arrest in human lung adenocarcinoma A549 cells without affecting apoptosis. The synergistic effects were consistently correlated with the up-regulation of cyclin-dependent kinases inhibitor proteins, including p16, p19, p21, and p27, as well as the repression of Cdk4 expression and nuclear translocation. Mechanistic investigations demonstrated that FoxO1/FoxO3a and p70S6K/4E-BP1, the molecules at downstream of Src-PI3K-Akt and mTOR signaling, were significantly suppressed by the combined use of Dasatinib and Rapamycin. Restraining Src and mTOR with small interfering RNA in A549 cells further confirmed that the Src/PI3K/mTOR Pathway played a crucial role in enhancing the anticancer effect of Dasatinib. In addition, this finding was also validated by a series of assays using another two NSCLC cell lines, NCI-H1706 and NCI-H460. Conclusively, our results suggested that the combinatory application of Src and mTOR inhibitors might be a promising therapeutic strategy for NSCLC treatment.

  5. Comparison of the anti-cancer effect of Disulfiram and 5-Aza-CdR on pancreatic cancer cell line PANC-1

    Science.gov (United States)

    Dastjerdi, Mehdi Nikbakht; Babazadeh, Zahra; Salehi, Mansour; Hashemibeni, Batool; Kazemi, Mohammad

    2014-01-01

    Background: Pancreatic cancer has poor prognosis by surgical and chemotherapy when it is diagnosed, so other anti-cancerous assistant therapeutic drugs are suggested e.g. epigenetic reversal of tumor-suppressor genes on promoter hypermethylation. 5-Aza-CdR is a nucleoside analog of DNMTi but it has long-term cytotoxicity effects. This study compares the anticancer effect of 5-Aza-CdR and Disulfiram potencies on PANC-1 cell line and up-regulation of p21. Materials and Methods: PANC-1 cell line was cultured in DMEM high glucose and treated by 5-Aza-CdR with 5 and 10 μM concentration for four days and 13 μM DSF (Diulfiram) for 24 hours. MS-PCR and RT-PCR were carried out to detect the methylation pattern and estimate the mRNA expression of RASSF1A and p21 in PANC-1. Result: MS-PCR demonstrated partial unmethylation after treatment with 5-Aza-CdR while there was no unmethylated band after DSF treatment. RT-PCR showed significant differences between re-expression of RASSF1A before and after treatment with 10 μM 5-Aza-CdR (P 0.05). The significant correlation was observed between RASSF1A re-expression and p21 up-regulation before and after treatment with 10 μM 5-Aza-CdR (P 0.05), while p21 up-regulation was significantly higher after DSF treatment (P < 0.01). Conclusion: Our findings indicated that 5-Aza-CdR induces the re-expression of RASSF1A and p21 up-regulation in PANC-1. DSF showed no epigenetic reversion while it affected p21 up-regulation. PMID:25221759

  6. The anti-cancer activity of noscapine: a review.

    Science.gov (United States)

    Mahmoudian, Massoud; Rahimi-Moghaddam, Parvaneh

    2009-01-01

    Noscapine is an isoqiunoline alkaloid found in opium latex. Unlike most other alkaloids obtained from opium latex, noscapine is not sedative and has been used as antitussive drug in various countries. Recently, it has been introduced as an anti-mitotic agent. This drug can be used orally. When the resistance to other anti-cancer drugs such as paclitaxel manifests, noscapine might be effective. Therefore, noscapine and its analogs have great potential as novel anti-cancer agents.

  7. Pheomelanin coat colour dilution in French cattle breeds is not correlated with the TYR, TYRP1 and DCT transcription levels.

    Science.gov (United States)

    Guibert, Sylvain; Girardot, Michael; Leveziel, Hubert; Julien, Raymond; Oulmouden, Ahmad

    2004-08-01

    In this study we report the isolation of full-length cDNAs and the expression patterns of TYR, TYRP1 and DCT in four e/e cattle breeds exhibiting different pheomelanic coat colours ranging from reddish brown to creamy white phenotypes. Predicted proteins encoded by bovine TYR, TYRP1 and DCT display high levels of homology and contain all characteristic domains shared between their mouse and human counterparts. The full expression of these three genes is observed in melanocytes of black areas of E(D)/E(D) Prim'Holstein's animals. On the other hand, e/e melanocytes of animals belonging to the Blonde d'Aquitaine (blond), Limousine (red) and Salers (reddish brown) breeds present different levels of down-regulated TYR and DCT expression and a complete repression of TYRP1. Surprisingly, e/e melanocytes of animals belonging to the Charolais breed (creamy white) present an inverse relationship between TYR, TYRP1 and DCT expression and its lower melanogenic activity. The sum of these results shows that the dilution of the coat colour in French cattle breeds is not correlated with a transcription level of TYR family genes. Other possible modifier loci are suggested.

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

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    Harris Adrian L

    2006-06-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusion 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

  9. HDAC inhibitors, MS-275 and salermide, potentiates the anticancer effect of EF24 in human pancreatic cancer cells

    Science.gov (United States)

    Yar Saglam, Atiye Seda; Yilmaz, Akin; Onen, Hacer Ilke; Alp, Ebru; Kayhan, Handan; Ekmekci, Abdullah

    2016-01-01

    Histone deacetylases (HDACs) play a major role in the regulation of chromatin structure and gene expression by changing acetylation status of histone and non-histone proteins. MS-275 (entinostat, MS) is a well-known benzamide-based HDACI and Salermide (SAL), a reverse amide compound HDACI, have antiproliferative effects on several human cancer cells. In this study, we aimed to investigate the effects of HDACIs (MS and SAL) alone and/or combined use with EF24 (EF), a novel synthetic curcumin analog, on human pancreatic cancer cell line (BxPC-3). In vitro, BxPC-3 cells were exposed to varying concentrations of MS, SAL with or without EF, and their effects on cell viability, acetylated Histone H3 and H4 levels, cytotoxicity, and cleaved caspase 3 levels, and cell cycle distribution were measured. The viability of BxPC-3 cells decreased significantly after treatment with EF, MS and SAL treatments. MS and SAL treatment increased the acetylation of histone H3 and H4 in a dose dependent manner. MS and SAL alone or combined with EF were increased the number of cells in G1 phase. In addition, treatment with agents significantly decreased the ratio of cell in G2/M phase. There were significant dose-dependent increases at cleaved Caspase 3 levels after MS treatment but not after SAL treatment. Our results showed that HDAC inhibitors (MS and SAL), when combined with EF, may effectively reduce pancreatic cancer cell (BxPC-3) progression and stop the cell cycle at G1 phase. Further molecular analyses are needed to understand the fundamental molecular consequences of HDAC inhibition in pancreas cancer cells. PMID:27330528

  10. Synergistic Anticancer Effects of Vorinostat and Epigallocatechin-3-Gallate against HuCC-T1 Human Cholangiocarcinoma Cells

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    Tae Won Kwak

    2013-01-01

    Full Text Available The aim of this study was to investigate the effect of the combination of vorinostat and epigallocatechin-3-gallate against HuCC-T1 human cholangiocarcinoma cells. A novel chemotherapy strategy is required as cholangiocarcinomas rarely respond to conventional chemotherapeutic agents. Both vorinostat and EGCG induce apoptosis and suppress invasion, migration, and angiogenesis of tumor cells. The combination of vorinostat and EGCG showed synergistic growth inhibitory effects and induced apoptosis in tumor cells. The Bax/Bcl-2 expression ratio and caspase-3 and -7 activity increased, but poly (ADP-ribose polymerase expression decreased when compared to treatment with each agent alone. Furthermore, invasion, matrix metalloproteinase (MMP expression, and migration of tumor cells decreased following treatment with the vorinostat and EGCG combination compared to those of vorinostat or EGCG alone. Tube length and junction number of human umbilical vein endothelial cells (HUVECs decreased as well as vascular endothelial growth factor expression following vorinostat and EGCG combined treatment. These results indicate that the combination of vorinostat and EGCG had a synergistic effect on inhibiting tumor cell angiogenesis potential. We suggest that the combination of vorinostat and EGCG is a novel option for cholangiocarcinoma chemotherapy.

  11. 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.

  12. Combination of salinomycin and silver nanoparticles enhances apoptosis and autophagy in human ovarian cancer cells: an effective anticancer therapy.

    Science.gov (United States)

    Zhang, Xi-Feng; Gurunathan, Sangiliyandi

    2016-01-01

    Ovarian cancer is one of the most important malignancies, and the origin, detection, and pathogenesis of epithelial ovarian cancer remain elusive. Although many cancer drugs have been developed to dramatically reduce the size of tumors, most cancers eventually relapse, posing a critical problem to overcome. Hence, it is necessary to identify possible alternative therapeutic approaches to reduce the mortality rate of this devastating disease. To identify alternative approaches, we first synthesized silver nanoparticles (AgNPs) using a novel bacterium called Bacillus clausii. The synthesized AgNPs were homogenous and spherical in shape, with an average size of 16-20 nm, which are known to cause cytotoxicity in various types of human cancer cells, whereas salinomycin (Sal) is able to kill cancer stem cells. Therefore, we selected both Sal and AgNPs to study their combined effect on apoptosis and autophagy in ovarian cancer cells. The cells treated with either Sal or AgNPs showed a dose-dependent effect with inhibitory concentration (IC)-50 values of 6.0 µM and 8 µg/mL for Sal and AgNPs, respectively. To determine the combination effect, we measured the IC25 values of both Sal and AgNPs (3.0 µM and 4 µg/mL), which showed a more dramatic inhibitory effect on cell viability and cell morphology than either Sal or AgNPs alone. The combination of Sal and AgNPs had more pronounced effect on cytotoxicity and expression of apoptotic genes and also significantly induced the accumulation of autophagolysosomes, which was associated with mitochondrial dysfunction and loss of cell viability. Our data show a strong synergistic interaction between Sal and AgNPs in tested cancer cells. The combination treatment increased the therapeutic potential and demonstrated the relevant targeted therapy for the treatment of ovarian cancer. Furthermore, we provide, for the first time, a mode of action for Sal and AgNPs in ovarian cancer cells: enhanced apoptosis and autophagy.

  13. Combination of salinomycin and silver nanoparticles enhances apoptosis and autophagy in human ovarian cancer cells: an effective anticancer therapy

    Directory of Open Access Journals (Sweden)

    Zhang XF

    2016-08-01

    Full Text Available Xi-Feng Zhang,1 Sangiliyandi Gurunathan2 1College of Biological and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan, People’s Republic of China; 2Department of Stem Cell and Regenerative Biology, Konkuk University, Seoul, South Korea Abstract: Ovarian cancer is one of the most important malignancies, and the origin, detection, and pathogenesis of epithelial ovarian cancer remain elusive. Although many cancer drugs have been developed to dramatically reduce the size of tumors, most cancers eventually relapse, posing a critical problem to overcome. Hence, it is necessary to identify possible alternative therapeutic approaches to reduce the mortality rate of this devastating disease. To identify alternative approaches, we first synthesized silver nanoparticles (AgNPs using a novel bacterium called Bacillus clausii. The synthesized AgNPs were homogenous and spherical in shape, with an average size of 16–20 nm, which are known to cause cytotoxicity in various types of human cancer cells, whereas salinomycin (Sal is able to kill cancer stem cells. Therefore, we selected both Sal and AgNPs to study their combined effect on apoptosis and autophagy in ovarian cancer cells. The cells treated with either Sal or AgNPs showed a dose-dependent effect with inhibitory concentration (IC-50 values of 6.0 µM and 8 µg/mL for Sal and AgNPs, respectively. To determine the combination effect, we measured the IC25 values of both Sal and AgNPs (3.0 µM and 4 µg/mL, which showed a more dramatic inhibitory effect on cell viability and cell morphology than either Sal or AgNPs alone. The combination of Sal and AgNPs had more pronounced effect on cytotoxicity and expression of apoptotic genes and also significantly induced the accumulation of autophagolysosomes, which was associated with mitochondrial dysfunction and loss of cell viability. Our data show a strong synergistic interaction between Sal and AgNPs in tested cancer cells. The combination

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

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    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.

  15. Effect of precursors feeding and media manipulation on production of novel anticancer pro-drug camptothecin from endophytic fungus.

    Science.gov (United States)

    Amna, Touseef; Amina, Musarat; Sharma, P R; Puri, S C; Al-Youssef, Hanan M; Al-Taweel, Areej M; Qazi, G N

    2012-10-01

    We have established methodology for the isolation and characterization of a novel endophytic fungus from the inner bark of medicinal plant Nothapodytes foetida, which produced camptothecin in Sabouraud broth (SB) under shake flask conditions. Camptothecin and its related compounds are at present obtained by extraction from intact plants, but fungal endopytes may be an alternative source of production. In present study we have observed the effect of different nutrient combinations and precursors (tryptophan, tryptamine, geraniol, citral, mevalonic acid and leucine) on the accumulation of camptothecin by endophytic fungus Entrophospora infrequens. The precursors were fed either alone or in combinations (tryptophan and geraniol, tryptophan and citral, tryptophan and mevalonic acid, tryptophan and leucine). The highest camptothecin content was observed in the range of 503 ± 25µg/100g dry cell mass in Sabouraud medium. Camptothecin content in the medium was increased by 2.5 folds by the presence of tryptophan and leucine whereas the production with trytophan was also significantly different from other treatments. Furthermore, the effect of fungal camptothecin on the morphology of human cancer cell lines was also studied. The treated cells showed reduction in size, condensation of nucleus and the protoplasmic extensions were reduced. All these characteristics are found in apoptotic cells.

  16. 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.

  17. 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

  18. Copper-obatoclax derivative complexes mediate DNA cleavage and exhibit anti-cancer effects in hepatocellular carcinoma.

    Science.gov (United States)

    Su, Jung-Chen; Chang, Jung-Hua; Huang, Jui-Wen; Chen, Peter P-Y; Chen, Kuen-Feng; Tseng, Ping-Hui; Shiau, Chung-Wai

    2015-02-25

    Obatoclax is an indole-pyrrole compound that induces cancer cell apoptosis through targeting the anti-apoptotic Bcl-2 protein family. Previously, we developed a series of obatoclax derivatives and studied their STAT3 inhibition-dependent activity against cancer cell lines. The obatoclax analog, prodigiosin, has been reported to mediate DNA cleavage in cancer cells by coordinating with copper complexes. To gain an understanding of copper-obatoclax complex activity, we applied obatoclax derivatives to examine their copper-mediated nuclease activity as a means to establish a basis for structure activity relationship. Replacement of the indole ring of obatoclax with furanyl, thiophenyl or Boc-indolyl rings reduced the DNA cleavage ability. The same effect was achieved through the replacement of the obatoclax pyrrolyl ring with thiazolidinedione and thioacetal. Among the compounds tested, we demonstrated that the complex of obatoclax or compound 7 with copper exhibited potent DNA strand scission which correlated with HCC cell growth inhibition.

  19. 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

    the 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....../kg of 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......Administration of apple juice, black currant juice, ora 1:1 combination of the two juices significantly decreased the level of the lipid peroxidation biomarker malondialdehyde in plasma of female rats, whereas the protein oxidation biomarker 2-amino-adipic semialdehyde, was significantly increased...

  20. A new series of diarylamides possessing quinoline nucleus: Synthesis, in vitro anticancer activities, and kinase inhibitory effect.

    Science.gov (United States)

    El-Gamal, Mohammed I; Khan, Mohammad Ashrafuddin; Abdel-Maksoud, Mohammed S; Gamal El-Din, Mahmoud M; Oh, Chang-Hyun

    2014-11-24

    Synthesis of a new series of diarylamides possessing 6,7-dimethoxy(dihydroxy)quinoline scaffold is described. Their in vitro antiproliferative activities against NCI-58 human cancer cell lines of nine different cancer types were tested. Compounds 1a and 1d-g showed the highest mean %inhibition values over the 58 cell line panel at 10 μM, and they were further tested in 5-dose testing mode to determine their IC50 values. The five compounds were more potent than Imatinib against all the cell lines of nine different cancer types. Compound 1g showed the highest potencies. It showed inhibitory effect against C-RAF kinase (76.65% at 10 μM concentration).

  1. Irinotecan Synergistically Enhances the Antiproliferative and Proapoptotic Effects of Axitinib In Vitro and Improves Its Anticancer Activity In Vivo

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    Bastianina Canu

    2011-03-01

    Full Text Available Aims: To demonstrate the synergistic antiproliferative and proapoptotic activity of irinotecan and axitinib in vitro and the improvement of the in vivo effects on angiogenesis and pancreatic cancer. Methods: Proliferation and apoptotic assays were performed on human dermal microvascular endothelial cells and pancreas cancer (MIAPaCa-2, Capan-1 cell lines exposed to SN-38, the active metabolite of irinotecan, axitinib, or their simultaneous combination for 72 hours. ERK1/2 and Akt phosphorylation, the vascular endothelial growth factor (VEGF, VEGF receptor-2, and thrombospondin-1 (TSP-1 concentration were measured by ELISAs. ATP7A and ABCG2 gene expression was performed with real-time polymerase chain reaction and SN-38 intracellular concentrations were measured by high-performance liquid chromatography. Capan-1 xenografts in nude mice were treated with irinotecan and axitinib alone or in simultaneous combination. Results: A strong synergistic effect on antiproliferative and proapoptotic activity was found with the axitinib/SN-38 combination on endothelial and cancer cells. ERK1/2 and Akt phosphorylation were significantly inhibited by lower concentrations of the combined drugs in all the cell lines. Axitinib and SN-38 combined treatment greatly inhibited the expression of the ATP7A and ABCG2 genes in endothelial and cancer cells, increasing the SN-38 intracellular concentration. Moreover, TSP-1 secretion was increased in cells treated with both drugs, whereas VEGFR-2 levels significantly decreased. In vivo administration of the simultaneous combination determined an almost complete regression of tumors and tumor neovascularization. Conclusions:In vitro results show the highly synergistic properties of simultaneous combination of irinotecan and axitinib on endothelial and pancreas cancer cells, suggesting a possible translation of this schedule into the clinics.

  2. Characteristic effect of an anticancer dinuclear platinum(II) complex on the higher-order structure of DNA.

    Science.gov (United States)

    Kida, Naoko; Katsuda, Yousuke; Yoshikawa, Yuko; Komeda, Seiji; Sato, Takaji; Saito, Yoshihiro; Chikuma, Masahiko; Suzuki, Mari; Imanaka, Tadayuki; Yoshikawa, Kenichi

    2010-06-01

    It is known that a 1,2,3-triazolato-bridged dinuclear platinum(II) complex, [{cis-Pt(NH(3))(2)}(2)(micro-OH)(micro-1,2,3-ta-N (1),N (2))](NO(3))(2) (AMTA), shows high in vitro cytotoxicity against several human tumor cell lines and circumvents cross-resistance to cisplatin. In the present study, we examined a dose- and time-dependent effect of AMTA on the higher-order structure of a large DNA, T4 phage DNA (166 kbp), by adapting single-molecule observation with fluorescence microscopy. It was found that AMTA induces the shrinking of DNA into a compact state with a much higher potency than cisplatin. From a quantitative analysis of the Brownian motion of individual DNA molecules in solution, it became clear that the density of a DNA segment in the compact state is about 2,000 times greater than that in the absence of AMTA. Circular dichroism spectra suggested that AMTA causes a transition from the B to the C form in the secondary structure of DNA, which is characterized by fast and slow processes. Electrophoretic measurements indicated that the binding of AMTA to supercoiled DNA induces unwinding of the double helix. Our results indicate that AMTA acts on DNA through both electrostatic interaction and coordination binding; the former causes a fast change in the secondary structure from the B to the C form, whereas the latter promotes shrinking in the higher-order structure as a relatively slow kinetic process. The shrinking effect of AMTA on DNA is attributable to the possible increase in the number of bridges along a DNA molecule. It is concluded that AMTA interacts with DNA in a manner markedly different from that of cisplatin.

  3. Progress in Research on the Anti-cancer Effect of Salinomycin%盐霉素抗肿瘤作用研究进展

    Institute of Scientific and Technical Information of China (English)

    张鹰; 王毅

    2013-01-01

    盐霉素(salinomycin)特异性杀伤肿瘤干细胞(cancer stem cell,CSC)作用的发现,引起了国内外学者的广泛关注.最近的研究表明,盐霉素能高选择性杀死小鼠身上的人乳腺癌CSC并且其效力比紫杉醇高100倍.盐霉素这种靶向作用于CSC的能力及较好的成药性,使其具有研发为一种新型的抗癌药物的潜能.通过手术及术后化疗抗癌的传统方法已经难以对抗肿瘤的复发或转移.然而,利用离子型载体抗生素即盐霉素杀伤肿瘤干细胞这一特性,消除肿瘤复发与转移的”根源”,从而达到治愈”癌症”这一顽疾的目的在理论上是可行的.多项研究已证实盐霉素能对抗多种肿瘤干细胞,因此我们认为盐霉素是一种广谱抗肿瘤药物,这些结论将推动临床抗肿瘤研究进入一个崭新的阶段,为防癌治癌工作提供实验依据和新的思路.本文将系统阐述盐霉素抗肿瘤药效学及其作用机制的研究进展,以期为后续临床研发抗癌新化合物提供参考.%The anti-cancer activity of salinomycin has evoked excitement at home and abroad,due to its recent identification as a selective inhibitor of cancer stem cells (CSCs) from tumorsphere.In view of recent findings,salinomycin could deplete the proportion of CSCs by > l00-fold relative to paclitaxel.The ability of salinomycin preferentially targets CSCs makes it possible to become a novel and effective anticancer agent.The traditional methods of surgery and postoperative chemotherapy have proved to be difficult to prevent recurrence of metastasis of tumor.However,it is possible in theory to kill cancer stem cells by using ionic carrier of antibiotic named salinomycin,the “trigger” of tumor relapse and metastasis,human-bing could achieve the goal of curing “cancer” eventually.Many studies have confirmed that salinomycin can fight against a variety of cancer stem cells,so we think salinomycin is a broad-spectrum antitumor drug

  4. In situ synthesized BSA capped gold nanoparticles: effective carrier of anticancer drug methotrexate to MCF-7 breast cancer cells.

    Science.gov (United States)

    Murawala, Priyanka; Tirmale, Amruta; Shiras, Anjali; Prasad, B L V

    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.

  5. Selective targeting of HDAC1/2 elicits anticancer effects through Gli1 acetylation in preclinical models of SHH Medulloblastoma

    Science.gov (United States)

    Coni, Sonia; Mancuso, Anna Barbara; Di Magno, Laura; Sdruscia, Giulia; Manni, Simona; Serrao, Silvia Maria; Rotili, Dante; Spiombi, Eleonora; Bufalieri, Francesca; Petroni, Marialaura; Kusio-Kobialka, Monika; De Smaele, Enrico; Ferretti, Elisabetta; Capalbo, Carlo; Mai, Antonello; Niewiadomski, Pawel; Screpanti, Isabella; Di Marcotullio, Lucia; Canettieri, Gianluca

    2017-01-01

    SHH Medulloblastoma (SHH-MB) is a pediatric brain tumor characterized by an inappropriate activation of the developmental Hedgehog (Hh) signaling. SHH-MB patients treated with the FDA-approved vismodegib, an Hh inhibitor that targets the transmembrane activator Smoothened (Smo), have shown the rapid development of drug resistance and tumor relapse due to novel Smo mutations. Moreover, a subset of patients did not respond to vismodegib because mutations were localized downstream of Smo. Thus, targeting downstream Hh components is now considered a preferable approach. We show here that selective inhibition of the downstream Hh effectors HDAC1 and HDAC2 robustly counteracts SHH-MB growth in mouse models. These two deacetylases are upregulated in tumor and their knockdown inhibits Hh signaling and decreases tumor growth. We demonstrate that mocetinostat (MGCD0103), a selective HDAC1/HDAC2 inhibitor, is a potent Hh inhibitor and that its effect is linked to Gli1 acetylation at K518. Of note, we demonstrate that administration of mocetinostat to mouse models of SHH-MB drastically reduces tumor growth, by reducing proliferation and increasing apoptosis of tumor cells and prolongs mouse survival rate. Collectively, these data demonstrate the preclinical efficacy of targeting the downstream HDAC1/2-Gli1 acetylation in the treatment of SHH-MB. PMID:28276480

  6. Novel ferrocenyl derivatives exert anti-cancer effect in human lung cancer cells in vitro via inducing G1-phase arrest and senescence

    Institute of Scientific and Technical Information of China (English)

    Ying LI; Han-lin MA; Lei HAN; Wei-yong LIU; Bao-xiang ZHAO; Shang-li ZHANG; Jun-ying MIAO

    2013-01-01

    Aim:To investigate the effects of 7 novel 1-ferrocenyl-2-(5-phenyl-1H-1,2,4-triazol-3-ylthio) ethanone derivatives on human lung cancer cells in vitro and to determine the mechanisms of action.Methods:A549 human lung cancer cells were examined.Cell viability was analyzed with MTT assay.Cell apoptosis and senescence were examined using Hoechst 33258 and senescence-associated-β-galactosidase (SA-β-gal) staining,respectively.LDH release was measured using a detection kit.Cell cycle was analyzed using a flow cytometer.Intracellular ROS level was measured with the 2',7'-dichlorodihydrofluorescein probe.Phosphorylation of p38 was determined using Western blot.Results:Compounds 5b,5d,and 5e (40 and 80 μmol/L) caused significant decrease of A549 cell viability,while other 4 compounds had no effect on the cells.Compounds 5b,5d,and 5e (80 μmol/L) induced G1-phase arrest (increased the G1 population by 22.6%,24.23%,and 26.53%,respectively),and markedly increased SA-β-gal-positive cells.However,the compounds did not cause nuclear DNA fragmentation and chromatin condensation in A549 cells.Nor did they affect the release of LDH from the cells.The compounds significantly elevated the intracellular ROS level,decreased the mitochondrial membrane potential,and increased p38 phosphorylation in the cells.In the presence of the antioxidant and free radical scavenger N-acetyl-L-cysteine (10 mmol/L),above effects of compounds 5b,5d,and 5e were abolished.Conclusion:The compounds 5b,5d,and 5e cause neither apoptosis nor necrosis of A549 cells,but exert anti-cancer effect via inducing G1-phase arrest and senescence through ROS/p38 MAP-kinase pathway.

  7. The interactions of anticancer agents with tea catechins: current evidence from preclinical studies.

    Science.gov (United States)

    Shang, Weihu; Lu, Weidong; Han, Mei; Qiao, Jinping

    2014-01-01

    Tea catechins exhibit a broad range of pharmacological activities that impart beneficial effects on human health. Epigallocatechin-3-gallate (EGCG), one of the major tea catechins, has been widely associated with cancer prevention and treatment. In addition, tea catechins in combination with anticancer drugs are being evaluated as a new cancer treatment strategy. However, the interactions of anticancer drugs with tea catechins are largely unknown. Accumulated data indicate significant interactions between anticancer drugs and tea catechins, such as synergistic tumor inhibition or antagonist activity. Therefore, it is critical to understand comprehensively the effects of tea catechins on anticancer drugs. Focusing on evidence from preclinical studies, this paper will review the interactions between anticancer drugs and tea catechins, including pharmacodynamics and pharmacokinetics effects. We hope that by detailing the interactions between anticancer drugs and tea catechins, more attention will be directed to this important therapeutic combination in the future.

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

    Directory of Open Access Journals (Sweden)

    Wei eLiting

    2015-06-01

    Full Text Available 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 contents of hydrogen peroxide (H2O2 and malondialdehyde (MDA. Under drought stress conditions, ABA markedly increased contents 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 contents 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

  9. Optimisation of transgene action at the post-transcriptional level: high quality parthenocarpic fruits in industrial tomatoes

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    Defez Roberto

    2002-01-01

    Full Text Available Abstract Background Genetic engineering of parthenocarpy confers to horticultural plants the ability to produce fruits under environmental conditions that curtail fruit productivity and quality. The DefH9-iaaM transgene, whose predicted action is to confer auxin synthesis specifically in the placenta, ovules and derived tissues, has been shown to confer parthenocarpy to several plant species (tobacco, eggplant, tomato and varieties. Results UC82 tomato plants, a typical cultivar used by the processing industry, transgenic for the DefH9-iaaM gene produce parthenocarpic fruits that are malformed. UC82 plants transgenic for the DefH9-RI-iaaM, a DefH9-iaaM derivative gene modified in its 5'ULR by replacing 53 nucleotides immediately upstream of the AUG initiation codon with an 87 nucleotides-long sequence derived from the rolA intron sequence, produce parthenocarpic fruits of high quality. In an in vitro translation system, the iaaM mRNA, modified in its 5'ULR is translated 3–4 times less efficiently than the original transcript. An optimal expressivity of parthenocarpy correlates with a reduced transgene mRNA steady state level in DefH9-RI-iaaM flower buds in comparison to DefH9-iaaM flower buds. Consistent with the known function of the iaaM gene, flower buds transgenic for the DefH9-RI-iaaM gene contain ten times more IAA than control untransformed flower buds, but five times less than DefH9-iaaM flower buds. Conclusions By using an auxin biosynthesis transgene downregulated at the post-transcriptional level, an optimal expressivity of parthenocarpy has been achieved in a genetic background not suitable for the original transgene. Thus, the method allows the generation of a wider range of expressivity of the desired trait in transgenic plants.

  10. Dwarifng apple rootstock responses to elevated temperatures:A study on plant physiological features and transcription level of related genes

    Institute of Scientific and Technical Information of China (English)

    ZHOU Bei-bei; SUN Jian; LIU Song-zhong; JIN Wan-mei; ZHANG Qiang; WEI Qin-ping

    2016-01-01

    The aim of this study was to investigate the impact of heat stress on physiological features, together with endogenous hormones and the transcription level of related genes, to estimate the heat resistance ability and stress injury mechanism of different dwarifng apple rootstocks. Among the six rootstocks, the rootstocks of native Shao series (SH series) showed better heat stress resistance than those of Budagovski 9 (B9), Cornel-Geneva 24 (CG24), and Maling 26 (M26) from abroad. Among SH series rootstocks, SH1 and SH6 showed higher heat stress resistance than SH40. M26 demonstrated the lowest adaption ability to heat stress, showing higher leaf conductivity and lower liquid water content (LWC) with the increase in temperature. Heat stress also resulted in the suppression of photosynthesis, which showed no signiifcant res-toration after 7-day recovery. It should be noted that although a higher temperature led to a lower LWC and photosynthetic efifciency (Pn) of CG24, there was no signiifcant increase in leaf conductivity, and 7 days after the treatment, thePn of CG24 recovered. The extremely high temperature tolerance of SH series rootstocks could be related to the greater osmotic ad-justment (OA), which was relfected by smaler reductions in leaf relative water content (RWC) and higher turgor potentials and leaf gas exchange compared with the other rootstocks. Determination of hormones indicated multivariate regulation, and it is presumed that a relatively stable expression levels of functional genes under high-temperature stress is necessary for heat stress resistance of rootstocks.

  11. Elucidation of major contributors involved in nitrogen removal and transcription level of nitrogen-cycling genes in activated sludge from WWTPs

    Science.gov (United States)

    Che, You; Liang, Peixin; Gong, Ting; Cao, Xiangyu; Zhao, Ying; Yang, Chao; Song, Cunjiang

    2017-01-01

    We investigated nitrogen-cycle bacterial communities in activated sludge from 8 municipal wastewater treatment plants (WWTPs). Redundancy analyses (RDA) showed that temperature was the most significant driving force in shaping microbial community structure, followed by influent NH4+ and total nitrogen (TN). The diversity of ammonia oxidizing and nitrite reducing bacteria were investigated by the construction of amoA, nirS and nirK gene clone libraries. Phylogenetic analysis indicated that Thauera and Mesorhizobium were the predominant nitrite reducing bacteria, and Nitrosomonas was the only detected ammonia oxidizing bacteria in all samples. Quantification of transcription level of nirS and nirK genes indicated that nirS-type nitrite reducing bacteria played the dominant roles in nitrite reduction process. Transcription level of nirS gene positively correlated with influent NH4+ and TN significantly, whereas inversely linked with hydraulic retention time. Temperature had a strong positive correlation to transcription level of amoA gene. Overall, this study deepened our understanding of the major types of ammonia oxidizing and nitrite reducing bacteria in activated sludge of municipal WWTPs. The relationship between transcription level of nitrogen-cycle genes and operational or environmental variables of WWTPs revealed in this work could provide guidance for optimization of operating parameters and improving the performance of nitrogen removal. PMID:28294196

  12. STEADY-STATE TRANSCRIPT LEVELS OF CYTOCHROME-C-OXIDASE GENES DURING HUMAN MYOGENESIS INDICATE SUBUNIT SWITCHING OF SUBUNIT VIA AND COEXPRESSION OF SUBUNIT VIIA ISOFORMS

    NARCIS (Netherlands)

    TAANMAN, JW; HERZBERG, NH; DEVRIES, H; BOLHUIS, PA; VANDENBOGERT, C

    1992-01-01

    Steady-state levels of the mitochondrial rRNAs, of mRNAs for mitochondrially and nuclear-encoded subunits of cytochrome c oxidase and for the beta-subunit of ATP synthase were assessed by Northern blot hybridizations during the in vitro differentiation of human myoblasts. Transcript levels of the so

  13. Sensitization for Anticancer Drug-Induced Apoptosis by Betulinic Acid

    Directory of Open Access Journals (Sweden)

    Simone Fulda

    2005-02-01

    Full Text Available We previously described that betulinic acid (BetA, a naturally occurring pentacyclic triterpenoid, induces apoptosis in tumor cells through the mitochondrial pathway. Here, for the first time, we provide evidence that BetA cooperated with anticancer drugs to induce apoptosis and to inhibit clonogenic survival of tumor cells. Combined treatment with BetA and anticancer drugs acted in concert to induce loss of mitochondrial membrane potential and the release of cytochrome c and Smac from mitochondria, resulting in activation of caspases and apoptosis. Overexpression of Bcl-2, which blocked mitochondrial perturbations, also inhibited the cooperative effect of BetA and anticancer drugs, indicating that cooperative interaction involved the mitochondrial pathway. Notably, cooperation of BetA and anticancer drugs was found for various cytotoxic compounds with different modes of action (e.g., doxorubicin, cisplatin, Taxol, VP16, or actinomycin D. Importantly, BetA and anticancer drugs cooperated to induce apoptosis in different tumor cell lines, including p53 mutant cells, and also in primary tumor cells, but not in human fibroblasts indicating some tumor specificity. These findings indicate that using BetA as sensitizer in chemotherapy-based combination regimens may be a novel strategy to enhance the efficacy of anticancer therapy, which warrants further investigation.

  14. The Study on Acute and Subacute Toxicity and Sarcoma-180 Anti-cancer Effects of Carthami Tinctor-Fructus Herbal-acupuncture(CF

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    Chang-Suk An

    2002-02-01

    Full Text Available Objective: The purpose of this study was to investigate acute and subacute toxicity and sarcoma-180 anti-cancer effects of herbal acupuncture with Carthami- Tinctorii fructus (CF in mice and rats. Method: Balb/c mice were injected intraperitoneally with Carthami - Tinctorii fructus (CF for LD50 and acute toxicity test. Sprague Dawley rats were injected intraperitoneally with Carthami- Tinctorii fructus (CF for subacute toxicity test. The Carthami- Tinctorii fructus herbal-acupuncture was injected on Chung-wan (CV12 of mice with Sarcoma-180 cancer cell line. Results: 1. LD50 was uncountable as none of the subjects expired during the test. 2. In acute toxicity test, toxic symptoms were not detected, but the body weight of mice was increased in treatment Ⅰ, treatment Ⅱ groups, compared to the normal group.(p<0.05 3. In acute toxicity test of serum biochemical values of mice, glucose was increased in treatment Ⅰ and treatment Ⅱ groups, total cholesterol was increased in treatment I group, GOT was decreased in treatment Ⅱ group, and GPT was decreased in treatment Ⅰ group, compared to the normal group.(p<0.05 4. The clinical signs and the body weight of mice treated with 0.1 cc, 0.2cc Carthami- Tinctorii fructus (CF were not affected during the subacute toxicity test. 5. In subacute toxicity test, treatment groups didn't show significant changes in complete blood count test (CBC of rats, compared to the nonnal group.(p<0.05 6. In subacute toxicity test of serum biochemical values of rats, uric acid was decreased in treatment Ⅰ and treatment Ⅱ groups, compared to the nonnal group, triglyceride was decreased in treatment I group, compared to the normal group, GOT and GPT were decreased in treatment I and treatment Ⅱ groups, and alkaline phosphatase was decreased in treatment Ⅰ and treatment Ⅱ groups, compared to the normal group.(p<0.05 7. Median survival time was increased in all the treatment groups for Sarcoma-180 cancer cell

  15. Anticancer Effect of PS-T on the Experimental Hepatocellular Carcinoma%对实验性肝癌中槐耳抗癌作用的研究

    Institute of Scientific and Technical Information of China (English)

    陈莉; 陆正鑫; 陆鹏; 李德生

    2004-01-01

    目的本文从病理角度在细胞水平上观察槐耳清膏的防癌与抑癌作用.方法联合应用二乙基亚硝胺(DENA)、四氯化碳复制鼠肝硬化肝癌模型,分为7组,在不同阶段灌服槐耳清膏进行干预癌形成,20周后处死鼠,进行病理观察.结果灌服槐耳清膏减缓鼠体重的下降,减轻癌变的病理变化,癌变率显著降低.槐耳也能通过抑制肝硬化干预癌的形成,其疗程与疗效呈显著正相关.结论在鼠肝癌模型制备中灌服槐耳清膏具有确切的防癌抑癌作用,槐耳清膏是临床抗肿瘤的理想药物,将成为肿瘤综合治疗及单独治疗的主干药物.%Objective: To apply PS-T in different phases of carcinoma formation and development, and research the mechanism of anti-carcinoma of PS-T in the cytological level. Methods: N-nitrosodiethylamine (DENA) and CCl4 were applied jointly to duplicate the rat hepatocirrhosis and hepatic cancer model. The rats were divided into 7 groups and were administrated via nasal-stomach tube with PS-T in different phases to interfere the cancer genesis and development. All the rats were killed in 20 weeks for pathological observation. Results: The loss of body weight of rats slowed down in the PS-T-treated group, and the carcinogenesis rate was significantly decreased correspondingly. PS-T could also inhibit the carcinogenesis by supressing the hepatocirrhosis, which showed the positive correlation between the curative effect and the curative period. Conclusion: Application of PS-T during cancer induction showed a significant effect on preventing and supressing cancer. PS-T might be an ideal drug for clinical anti-cancer therapy. And it will be a main drug in both combined and single treatments for tumor.

  16. Anticancer Effect and Structure-Activity Analysis of Marine Products Isolated from Metabolites of Mangrove Fungi in the South China Sea

    Directory of Open Access Journals (Sweden)

    Li-yang Tao

    2010-04-01

    Full Text Available Marine-derived fungi provide plenty of structurally unique and biologically active secondary metabolites. We screened 87 marine products from mangrove fungi in the South China Sea for anticancer activity by MTT assay. 14% of the compounds (11/86 exhibited a potent activity against cancer in vitro. Importantly, some compounds such as compounds 78 and 81 appeared to be promising for treating cancer patients with multidrug resistance, which should encourage more efforts to isolate promising candidates for further development as clinically useful chemotherapeutic drugs. Furthermore, DNA intercalation was not involved in their anticancer activities, as determined by DNA binding assay. On the other hand, the structure-activity analysis indicated that the hydroxyl group was important for their cytotoxic activity and that bulky functional groups such as phenyl rings could result in a loss of biological activity, which will direct the further development of marine product-based derivatives.

  17. Anticancer effect and structure-activity analysis of marine products isolated from metabolites of mangrove fungi in the South China Sea.

    Science.gov (United States)

    Tao, Li-yang; Zhang, Jian-ye; Liang, Yong-ju; Chen, Li-ming; Zhen, Li-sheng; Wang, Fang; Mi, Yan-jun; She, Zhi-gang; To, Kenneth Kin Wah; Lin, Yong-cheng; Fu, Li-wu

    2010-04-01

    Marine-derived fungi provide plenty of structurally unique and biologically active secondary metabolites. We screened 87 marine products from mangrove fungi in the South China Sea for anticancer activity by MTT assay. 14% of the compounds (11/86) exhibited a potent activity against cancer in vitro. Importantly, some compounds such as compounds 78 and 81 appeared to be promising for treating cancer patients with multidrug resistance, which should encourage more efforts to isolate promising candidates for further development as clinically useful chemotherapeutic drugs. Furthermore, DNA intercalation was not involved in their anticancer activities, as determined by DNA binding assay. On the other hand, the structure-activity analysis indicated that the hydroxyl group was important for their cytotoxic activity and that bulky functional groups such as phenyl rings could result in a loss of biological activity, which will direct the further development of marine product-based derivatives.

  18. Anticancer Effect and Structure-Activity Analysis of Marine Products Isolated from Metabolites of Mangrove Fungi in the South China Sea

    OpenAIRE

    Li-yang Tao; Jian-ye Zhang; Yong-ju Liang; Li-ming Chen; Li-sheng Zheng; Fang Wang; Yan-jun Mi; Zhi-gang She; Kenneth Kin Wah To; Yong-cheng Lin; Li-wu Fu

    2010-01-01

    Marine-derived fungi provide plenty of structurally unique and biologically active secondary metabolites. We screened 87 marine products from mangrove fungi in the South China Sea for anticancer activity by MTT assay. 14% of the compounds (11/86) exhibited a potent activity against cancer in vitro. Importantly, some compounds such as compounds 78 and 81 appeared to be promising for treating cancer patients with multidrug resistance, which should encourage more efforts to isolate promising can...

  19. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Berberine Induces Apoptosis in p53-Null Leukemia Cells by Down-Regulating XIAP at the Post-Transcriptional Level

    Directory of Open Access Journals (Sweden)

    Jian Liu

    2013-11-01

    Full Text Available Background: Berberine exerts anticancer activities both in vitro and in vivo through different mechanisms. However, the underlying molecular mechanisms of berberine induced p53-independent apoptosis remain unclear. Methods: The p53-null leukemia cell line EU-4 cells were exposed to berberine. Then the cell viability and apoptosis were determined. Western blot and PCR were employed to detect the expression of apoptosis related protein, XIAP and MDM2. Small interfering RNA (siRNA was applied to knock down endogenous expression of MDM2 and XIAP. Results: Berberine induced p53-independent, XIAP-mediated apoptotic cell death in p53-null leukemia cells. Treatment with berberine resulted in suppression of XIAP protein in a dose- and time- dependent manner. Berberine induced down-regulation of XIAP protein involving inhibition of MDM2 expression and a proteasome-dependent pathway. Moreover, inhibition of XIAP by berberine or siRNA increased the sensitivity of leukemia cells to doxorubicin-induced apoptosis. Conclusion: Our findings characterize the molecular mechanisms of berberine-induced caspase activation and subsequent apoptosis, and berberine may be a novel candidate inducer of apoptosis in leukemia cells, which normally lack p53 expression.

  2. Anticancer properties of polysaccharides isolated from fungi of the Basidiomycetes class.

    Science.gov (United States)

    Lemieszek, Marta; Rzeski, Wojciech

    2012-01-01

    Basidiomycete mushrooms represent a valuable source of biologically active compounds with anticancer properties. This feature is primarily attributed to polysaccharides and their derivatives. The anticancer potential of polysaccharides is linked to their origin, composition and chemical structure, solubility and method of isolation. Moreover, their activity can be significantly increased by chemical modifications. Anticancer effects of polysaccharides can be expressed indirectly (immunostimulation) or directly (cell proliferation inhibition and/or apoptosis induction). Among the wide range of polysaccharides with documented anticancer properties, lentinan, polysaccharide-K (PSK) and schizophyllan deserve special attention. These polysaccharides for many years have been successfully applied in cancer treatment and their mechanism of action is the best known.

  3. Non-covalent carriage of anticancer agents by humanized antibody trastuzumab.

    Science.gov (United States)

    Yadav, Arpita; Sharma, Sweta; Yadav, Veejendra Kumar

    2016-05-01

    This article explores the internalization and non-covalent carriage of small molecule anticancer agents like vinca alkaloids by humanized monoclonal antibody trastuzumab. Such carriage is marked by significant reduction in side effects and increased therapeutic value of these anticancer agents. This study is coherent with few clinical observations of enhanced efficiency of these anticancer agents when co-administered with therapeutic antibodies. This study will also serve as the foundation for screening a database of anticancer agents for possible compounds that may be co-delivered alongwith the antibody. Based on this study vincristine conformation inside antibody and its charge environment may be used as descriptors for screening purposes.

  4. 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

  5. Reactions and interactions in handling anticancer drugs.

    Science.gov (United States)

    D'Arcy, P F

    1983-01-01

    The clinical toxicity of anticancer drugs has been well documented with regard to the adverse effects of treatment in patients. However, many of these drugs have a direct irritant effect on the skin, eyes, mucous membranes, and other tissues. Handled without due care, especially when being prepared for injection, most cytotoxic drugs can cause local toxic or allergic reactions; they also present hazards of carcinogenicity and mutagenicity. This spectrum of potential risk should be kept in mind by personnel administering or handling these drugs, especially in oncology units where just a few individuals may routinely and frequently reconstitute many doses of cytotoxic agents. This is work in which the hospital pharmacist should and must be involved; indeed, many of the techniques and skills required are identical with those used in standard aseptic procedures for preparing pharmaceutical products. Pharmacy departments should take the initiative in making hospital staff aware of the potential risks of handling neoplastic agents, and they should spearhead a multidisciplinary assessment for producing local guidelines for working with these drugs. This article warns practitioners about the inherent dangers of these practitioner-drug interactions and suggests ways in which they may be reduced. Information is given in tabular form regarding recommended procedures for reconstituting 24 anticancer drugs and precautions to protect the personnel handling them, especially when there is spillage of powdered or liquid drugs. Also, guidelines are given about incompatibilities with admixtures of such drugs, and the literature is reviewed relative to recent developments in hospital pharmacy departments where reconstitution of anticancer drugs has been incorporated into existing intravenous fluid preparation/admixture units. Not only has this been shown to be safer and more effective in terms of time and labor, but also it has cut the cost of injectable cytotoxic drugs by an

  6. Observed Effection of Solid Tumors by Percutaneous to Inject Anticancer Milk%实体瘤经皮注射抗癌乳疗效观察

    Institute of Scientific and Technical Information of China (English)

    温海华; 刘静

    2014-01-01

    目的进一步探索和观察抗癌乳的抗癌效果和临床应用安全性。拓宽其临床应用范围。方法我科对63例实体瘤经皮穿刺注射抗癌乳,4w后复查,用WHO对实体瘤的疗效评价标准,评判其疗效;再与文献报道的实体瘤经皮植入放射微粒125I的临床对应指标相比较。进一步明确抗癌乳对实体瘤的临床治疗价值和优势。结果本组63例中,RR 76.18%CBR 93.64%。获得平均6个月PFS。与125I微粒比较,两者有效率为76.18%VS(73.14%~77.8%),PFS、本组平均6个月,与文献报道的125I粒子植入术后,累计91.67%患者无进展生存期为6月比较,极为相近。差异无统计学意义。结论抗癌乳与125I微粒比较,两者有效率和无进展生存期极为相近,无统计学差异。但在更加廉价易得、保存储运和使用安全方便等方面,抗癌乳则更具优势。在基层医院更适合于无手术指征实体瘤患者的治疗。%Objective Further exploration and observation of anticancer milk anti-cancer ef ect and safety for clinical application. To broaden the scope of clinical application. Methods In our department, 63 patients with solid tumors by percutaneous injection of anticancer milk, after 4 weeks,the standard to evaluate the ef ect of solid tumors with WHO, to judge its curative ef ect; then with the reported solid tumor by clinical corresponding index skin implanted radioactive particles 125I compared. To further clarify the anticancer milk for solid tumors in the clinical value and advantages. Results The 63 patients, RR 76.18% CBR 93.64%. For an average of 6 months PFS. With 125I particles implantation compared, The RR of 76.18%VS (73.14%~77.8%),PFS,In this group, with an average of 6 months. Compared 125I particle implantation was reported in the literature, a total of 91.67% patients were progression free survival was June, very close. No significant differences. Conclusion Anticancer milk compared with 125I particles, both efficient

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

    Science.gov (United States)

    Turánek, Jaroslav; Wang, Xiu-Fang; Knötigová, Pavlína; Koudelka, Stepán; Dong, Lan-Feng; Vrublová, Eva; Mahdavian, Elahe; Procházka, Lubomír; Sangsura, Smink; Vacek, Antonín; Salvatore, Brian A; Neuzil, Jiri

    2009-06-15

    The vitamin E analogue alpha-tocopheryl succinate (alpha-TOS) is an efficient anti-cancer drug. Improved efficacy was achieved through the synthesis of alpha-tocopheryl maleamide (alpha-TAM), an esterase-resistant analogue of alpha-tocopheryl maleate. In vitro tests demonstrated significantly higher cytotoxicity of alpha-TAM towards cancer cells (MCF-7, B16F10) compared to alpha-TOS and other analogues prone to esterase-catalyzed hydrolysis. However, in vitro models demonstrated that alpha-TAM was cytotoxic to non-malignant cells (e.g. lymphocytes and bone marrow progenitors). Thus we developed lyophilized liposomal formulations of both alpha-TOS and alpha-TAM to solve the problem with cytotoxicity of free alpha-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 alpha-TAM, which significantly reduced the growth of cancer cells in hollow fiber implants. Moreover, liposomal formulation of alpha-TAM and alpha-TOS each prevented the growth of tumours in transgenic FVB/N c-neu mice bearing spontaneous breast carcinomas. Liposomal formulation of alpha-TAM demonstrated anti-cancer activity at levels 10-fold lower than those of alpha-TOS. Thus, the liposomal formulation of alpha-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.

  8. 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

  9. Induction of miR-137 by Isorhapontigenin (ISO) Directly Targets Sp1 Protein Translation and Mediates Its Anticancer Activity Both In Vitro and In Vivo.

    Science.gov (United States)

    Zeng, Xingruo; Xu, Zhou; Gu, Jiayan; Huang, Haishan; Gao, Guangxun; Zhang, Xiaoru; Li, Jingxia; Jin, Honglei; Jiang, Guosong; Sun, Hong; Huang, Chuanshu

    2016-03-01

    Our recent studies found that isorhapontigenin (ISO) showed a significant inhibitory effect on human bladder cancer cell growth, accompanied with cell-cycle G0-G1 arrest as well as downregulation of Cyclin D1 expression at transcriptional level via inhibition of Sp1 transactivation in bladder cancer cells. In the current study, the potential ISO inhibition of bladder tumor formation has been explored in a xenograft nude mouse model, and the molecular mechanisms underlying ISO inhibition of Sp1 expression and anticancer activities have been elucidated both in vitro and in vivo. Moreover, the studies demonstrated that ISO treatment induced the expression of miR-137, which in turn suppressed Sp1 protein translation by directly targeting Sp1 mRNA 3'-untranslated region (UTR). Similar to ISO treatment, ectopic expression of miR-137 alone led to G0-G1 cell growth arrest and inhibition of anchorage-independent growth in human bladder cancer cells, which could be completely reversed by overexpression of GFP-Sp1. The inhibition of miR-137 expression attenuated ISO-induced inhibition of Sp1/Cyclin D1 expression, induction of G0-G1 cell growth arrest, and suppression of cell anchorage-independent growth. Taken together, our studies have demonstrated that miR-137 induction by ISO targets Sp1 mRNA 3'-UTR and inhibits Sp1 protein translation, which consequently results in reduction of Cyclin D1 expression, induction of G0-G1 growth arrest, and inhibition of anchorage-independent growth in vitro and in vivo. Our results have provided novel insights into understanding the anticancer activity of ISO in the therapy of human bladder cancer.

  10. Synergetic anticancer effect of combined quercetin and recombinant adenoviral vector expressing human wild-type p53, GM-CSF and B7-1 genes on hepatocellular carcinoma cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Ming Shi; Fu-Sheng Wang; Zu-Ze Wu

    2003-01-01

    AIM: This study investigated the anti-cancer effect ofcombined quercetin and a recombinant adenovirus vectorexpressing the human p53, GM-CSF and B7-1 genes(designated BB-102) on human hepatocellular carcinoma(HCC) cell lines in vitro.METHODS: The sensitivity of HCC cells to anticancer agentswas evaluated by 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The viability of cells infectedwith BB-102 was determined by trypan blue exclusion. Theexpression levels of human wild-type p53, GM-CSF and B7-1genes were determined by Western blot, enzyme-linkedimmunosorbent assay (ELISA) and flow cytometric analysis,respectively. The apoptosis of BB-102-infected or quercetin-treated HCC cells was detected by terminal deoxynucleotidyltransferase (TdT) assay or DNA ladder electrophoresis.RESULTS: Quercetin was found to suppress proliferation ofhuman HCC cell lines BEL-7402, HUH-7 and HLE, with peaksuppression at 50 μmol/L quercetin. BB-102 infection wasalso found to significantly suppress proliferation of HCC celllines. The apoptosis of BB-102-infected HCC cells was greaterin HLE and HUH-7 cells than in BEL-7402 cells. Quercetin didnot affect the expression of the three exogenous genes inBB-102-infected HCC cells (P>0.05), but it was found to furtherdecrease proliferation and promote apoptosis of BB-102-infected HCC cells.CONCLUSION: BB-102 and quercetin synergeticallysuppress HCC cell proliferation and induce HCC cell apoptosis,suggesting a possible use as a combined anti-cancer agent.

  11. Efficient use of artificial micro-RNA to downregulate the expression of genes at the post-transcriptional level in Arabidopsis thaliana.

    Science.gov (United States)

    Ud-Din, A; Rauf, M; Ghafoor, S; Khattak, M N K; Hameed, M W; Shah, H; Jan, S; Muhammad, K; Rehman, A; Inamullah

    2016-04-07

    Micro-RNAs are cellular components regulating gene expression at the post-transcription level. In the present study, artificial micro-RNAs were used to decrease the transcript level of two genes, AtExpA8 (encoding an expansin) and AHL25 (encoding an AT-hook motif nuclear localized protein) in Arabidopsis thaliana. The backbone of the Arabidopsis endogenous MIR319a micro-RNA was used in a site-directed mutagenesis approach for the generation of artificial micro-RNAs targeting two genes. The recombinant cassettes were expressed under the control of the CaMV 35S promoter in individual A. thaliana plants. Transgenic lines of the third generation were tested by isolating total RNA and by subsequent cDNA synthesis using oligo-dT18 primers and mRNAs as templates. The expression of the two target genes was checked through quantitative real-time polymerase chain reaction to confirm reduced transcript levels for AtExpA8 and AHL25. Downregulation of AtExpA8 resulted in the formation of short hypocotyls compared with those of the wild-type control in response to low pH and high salt concentration. This technology could be used to prevent the expression of exogenous and invading genes posing a threat to the normal cellular physiology of the host plant.

  12. 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.

  13. Artemisinin–Second Career as Anticancer Drug?

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    Thomas Efferth

    2015-10-01

    Full Text Available Artemisinin represents a showcase example not only for the activity of medicinal herbs deriving from traditional chinese medicine, but for phytotherapy in general. Its isolation from Sweet Wormwood (qinhao, Artemisia annua L. represents the starting point for an unprecedent success story in the treatment of malaria worldwide. Beyond the therapeutic value against Plasmodium parasites, it turned out in recent years that the bioactivity of artemisinin is not restricted to malaria. We and others found that this sesquiterpenoid also exerts profound anticancer activity in vitro and in vivo. Artemisinin-type drugs exert multi-factorial cellular and molecular actions in cancer cells. Ferrous iron reacts with artemisinin, which leads to the formation of reactive oxygen species and ultimately to a plethora anticancer effects of artemisinins, e.g. expression of antioxidant response genes, cell cycle arrest (G1 as well as G2 phase arrests, DNA damage that is repaird by base excision repair, homogous recombination and non-homologous end-joining, as well as different modes of cell death (intrinsic and extrinsic apoptosis, autophagy, necrosis, necroptosis, oncosis, and ferroptosis. Furthermore, artemisinins inhibit neoangiogenesis in tumors. The signaling of major transcription factors (NF-κB, MYC/MAX, AP-1, CREBP, mTOR etc. and signaling pathways are affected by artemisinins (e.g. Wnt/β-catenin pathway, AMPK pathway, metastatic pathways, nitric oxide signaling, and others. Several case reports on the compassionate use of artemisinins as well as clinical Phase I/II pilot studies indicate the clinical activity of artemisinins in veterinary and human cancer patients. Larger scale of Phase II and III clinical studies are required now to further develop artemisinin-type compounds as novel anticancer drugs.

  14. Fungal metabolites with anticancer activity.

    Science.gov (United States)

    Evidente, Antonio; Kornienko, Alexander; Cimmino, Alessio; Andolfi, Anna; Lefranc, Florence; Mathieu, Véronique; Kiss, Robert

    2014-05-01

    Covering: 1964 to 2013. Natural products from bacteria and plants have played a leading role in cancer drug discovery resulting in a large number of clinically useful agents. In contrast, the investigations of fungal metabolites and their derivatives have not led to a clinical cancer drug in spite of significant research efforts revealing a large number of fungi-derived natural products with promising anticancer activity. Many of these natural products have displayed notable in vitro growth-inhibitory properties in human cancer cell lines and select compounds have been demonstrated to provide therapeutic benefits in mouse models of human cancer. Many of these compounds are expected to enter human clinical trials in the near future. The present review discusses the reported sources, structures and biochemical studies aimed at the elucidation of the anticancer potential of these promising fungal metabolites.

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

    Energy Technology Data Exchange (ETDEWEB)

    Nagy, Edit, E-mail: edit.nagy@karolinska.se [Department of Medicine, Karolinska Institutet, Stockholm (Sweden); Department of Cardiology, Karolinska University Hospital, Stockholm (Sweden); Caidahl, Kenneth [Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm (Sweden); Department of Clinical Physiology, Karolinska University Hospital, Stockholm (Sweden); Franco-Cereceda, Anders [Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm (Sweden); Department of Throracic Surgery, Karolinska University Hospital, Stockholm (Sweden); Baeck, Magnus [Department of Medicine, Karolinska Institutet, Stockholm (Sweden); Department of Cardiology, Karolinska University Hospital, Stockholm (Sweden)

    2012-04-13

    Highlights: Black-Right-Pointing-Pointer Oxidative stress has been implicated in the pathomechanism of calcific aortic valve stenosis. Black-Right-Pointing-Pointer We assessed the transcript levels for PARP-1 (poly(ADP-ribose) polymerase), acts as a DNA damage nick sensor in stenotic valves. Black-Right-Pointing-Pointer Early stage of diseased tricuspid valves exhibited higher mRNA levels for PARP-1 compared to bicuspid valves. Black-Right-Pointing-Pointer The mRNA levels for PARP-1 inversely correlated with the clinical stenosis severity in tricuspid valves. Black-Right-Pointing-Pointer 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 C{sub 4} (LTC{sub 4}) 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

  16. Alkaloids Isolated from Natural Herbs as the Anticancer Agents

    Directory of Open Access Journals (Sweden)

    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.

  17. Autophagy modulation as a target for anticancer drug discovery

    Institute of Scientific and Technical Information of China (English)

    Xin LI; Huai-long XU; Yong-xi LIU; Na AN; Si ZHAO; Jin-ku BAO

    2013-01-01

    Autophagy,an evolutionarily conserved catabolic process involving the engulfment and degradation of non-essential or abnormal cellular organelles and proteins,is crucial for homeostatic maintenance in living cells.This highly regulated,multi-step process has been implicated in diverse diseases including cancer.Autophagy can function as either a promoter or a suppressor of cancer,which makes it a promising and challenging therapeutic target.Herein,we overview the regulatory mechanisms and dual roles of autophagy in cancer.We also describe some of the representative agents that exert their anticancer effects by regulating autophagy.Additionally,some emerging strategies aimed at modulating autophagy are discussed as having the potential for future anticancer drug discovery.In summary,these findings will provide valuable information to better utilize autophagy in the future development of anticancer therapeutics that meet clinical requirements.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. 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.

    Science.gov (United States)

    Flasiński, Michał; Hąc-Wydro, Katarzyna; Wydro, Paweł; Dynarowicz-Łątka, Patrycja

    2014-06-01

    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 (HL-60) and promyeloblastic leukaemia cells (K-562). As these cells differ essentially in the cholesterol/phospholipid ratio and plasmalogen concentration in the membrane, we have carried out systematic investigations in artificial systems of various compositions. The results for model leukaemia cell membrane were compared with data acquired for systems imitating normal leucocytes. Our results show that the level of plasmalogens significantly modulates the influence of the single-chained phospholipids on the investigated systems. The experiments confirmed also that the interactions of ether lipids with a model membrane of HL-60 cells (in biological tests sensitive to ED) have opposite character when compared with K-562, being resistant to ED. Moreover, the values of the parameters characterizing monolayers serving as membrane models (strength of interactions, monolayers fluidity and morphology) proved both sensitivity of these cells to ED and lack of their susceptibility towards PAF. Interestingly, it has been found that lyso-PAF, which is usually described as an inactive precursor of PAF, displays a stronger effect on HL-60 model membranes than ED.

  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.

  1. Geldanamycin and its anti-cancer activities.

    Science.gov (United States)

    Fukuyo, Yayoi; Hunt, Clayton R; Horikoshi, Nobuo

    2010-04-01

    Geldanamycin is a benzoquinone ansamycin antibiotic that manifests anti-cancer activity through the inhibition of HSP90-chaperone function. The HSP90 molecular chaperone is expressed at high levels in a wide variety of human cancers including melanoma, leukemia, and cancers in colon, prostate, lung, and breast. In cancer cells dependent upon mutated and/or over-expressed oncogene proteins, HSP90 is thought to have a critical role in regulating the stability, folding, and activity of HSP90-associated proteins, so-called "client proteins". These client proteins include the growth-stimulating proteins and kinases that support malignant transformation. Recently, oncogenic activating BRAF mutants have been identified in variety of cancers where constitutive activation of the MEK/ERK MAPK signaling pathway is the key for tumorigenesis, and they have been shown to be client proteins for HSP90. Accordingly, HSP90 inhibition can suppress certain cancer-causing client proteins and therefore represents an important therapeutic target. The molecular mechanism underlying the anti-cancer effect of HSP90 inhibition is complicated. Geldanamycin and its derivatives have been shown to induce the depletion of mutationally-activated BRAF through several mechanisms. In this review, we will describe the HSP90-inhibitory mechanism, focusing on recent progress in understanding HSP90 chaperone structure-function relationships, the identification of new HSP90 client proteins and the development of HSP90 inhibitors for clinical applications.

  2. 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.

  3. In vitro effects of combinations of cis-amminedichloro (2-methylpyridine) platinum (II) (ZD0473) with other novel anticancer drugs on the growth of SBC-3, a human small cell lung cancer cell line.

    Science.gov (United States)

    Kanzawa, F; Akiyama, Y; Saijo, N; Nishio, K

    2003-06-01

    Among numerous clinical regimens of combination chemotherapy, synergy has been observed to be particularly marked with combinations containing cisplatin (CDDP). However, the clinical use of CDDP has sometimes been limited by acquired resistance. The new-generation platinum drug, ZD0473, was synthesized with the aim of hindering the reaction of the drug with thiols, by the introduction of a 2-methylpyridine ligand. This enables the drug to exert antitumor activity against cisplatin-resistant cancer cells with elevated glutathione and/or metallothionein levels. The drug was also shown experimentally to overcome cisplatin resistance due to impaired drug accumulation, and enhanced DNA repair/tolerance to platinum-DNA adducts. We investigated the effects of combinations of ZD0473 with other anticancer drugs on the growth of a human small-cell lung cancer cell line (SBC-3). Six novel anticancer drugs were tested: docetaxel (TXT), paclitaxel (TXL), vinorelbine (VNB), irinotecan (CPT-11), gemcitabine (GEM) and pemetrexed (MTA). The growth inhibitory effect of the drugs was measured by MTT assay and the effects of the combination regimens were evaluated by the combination index analysis method developed by Chou and Talalay. Synergy was demonstrated for the combination regimens of ZD0473-GEM and ZD0473-TXL, while an additive effect was observed with combinations containing TXT, VNB, CPT-11 or MTA. In the case of the ZD0473-GEM combination, synergy was observed over a wide range of inhibition levels at dose ratios of 50:1, 100:1 and 250:1. The level of synergy was equivalent to that observed for combinations of CDDP-etoposide, CDDP-GEM and nedaplatin-CPT-11. The results suggest that the combination of ZD0473 with GEM merits further investigation in small cell lung cancer.

  4. 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

  5. 白三烯B4在塞来昔布介导的抗癌效应中的作用%Role of LTB4 in celecoxib-mediated anti-cancer effect

    Institute of Scientific and Technical Information of China (English)

    管蕾; 高鹏; 郑杰

    2011-01-01

    Objective To investigate the role of leukotriene B4 (LTB4) in celecoxib (a cyclooxygenase-2 inhibitor)-mediated anti-cancer effect. Methods The effects of celecoxib, LTB4 and nordihydroguaiaretic acid(NDGA) on the viability of human colon cancer HT-29 cells and human prostate cancer PC-3 cells as well as LTB4 addition on celecoxib-mediated anticancer effect were determined by MTT assay. Effects of celecoxib on the production of prostaglandin E2 (PGE2) and LTB4 in the both cancer cell lines were detected by ELISA. Results After treatment with celecoxib, the cell survival and expression of LTB4 were decreased in the both cell lines(P<0. 05 or P<0. 01), and only the expression of PGE2 was down-regulated in HT-29 cells ( P< 0. 01 ). Moreover, the inhibitory effect of celecoxib on HT-29 cell survival was antagonized by incubation with LTB4 (P< 0. 01) ,and HT-29 cell survival was significantly inhibited by NDGA ( P< 0. 01 ), which were not obviously changed in PC-3 cells. Conclusion Anti-cancer effect of celecoxib is cyclooxygenase-2independent in HT-29 and PC-3 cells, whereas only in HT-29 cells, celecoxib plays a role in anti-cancer via down-regulating LTB4 production.%目的 研究白三烯B4(LTB4)在环氧合酶2(COX-2)抑制剂塞来昔布介导的抗癌效应中的作用.方法 MTT法检测塞来昔布、LTB4和去甲二氢愈创木酸(NDGA)对人结肠癌HT-29细胞和人前列腺癌PC-3细胞生存的影响以及LTB4对塞来昔布抗癌效应的影响.ELISA法检测塞来昔布对癌细胞中前列腺素E2(PGE2)和LTB4表达的影响.结果 塞来昔布抑制HT-29和PC-3细胞的生存及LTB4表达(P<0.05或P<0.01),但仅下调HT-29细胞的PGE2表达(P<0.01).LTB4能拮抗塞来昔布对HT-29细胞生长的抑制作用(P<0.01),NDGA明显抑制HT-29细胞的生存(P<0.01),而对PC-3细胞则没有这些作用.结论 塞来昔布对HT-29和PC-3细胞的抑制效应是COX-2非依赖性的,且只有在HT-29细胞中,塞来昔布的抗癌

  6. Liposomal anticancer therapy: pharmacokinetic and clinical aspects.

    Science.gov (United States)

    Di Paolo, A

    2004-11-01

    Liposomes, which are vesicles composed of a phospholipid bilayer surrounding an aqueous milieu, represent a new strategy for anticancer drug delivery. Extravasation and accumulation of liposomal drugs within neoplastic tissues are possible because of the leaky vasculature and scarce lymphatic vessels of tumours (the enhanced permeability and retention effect). Furthermore, liposomal chemotherapeutic agents display distinctive pharmacokinetic characteristics, because they possess longer elimination half-lives, reduced clearance and smaller volume of distribution with respect to corresponding free drugs. Taken together, these features lead to highest levels of cytotoxic agents in tumours, as demonstrated in preclinical models and clinical trials, whereas healthy tissues are spared from toxicity. In fact, liposomal drugs (i.e., doxorubicin), alone or in combination with other cytotoxic agents, lead to improved clinical effectiveness and ameliorated toxicity profile with respect to corresponding free drugs when they are used for the treatment of metastatic breast and ovarian cancers, and Kaposi's sarcoma.

  7. Fenbendazole as a Potential Anticancer Drug

    Science.gov (United States)

    DUAN, QIWEN; LIU, YANFENG; ROCKWELL, SARA

    2013-01-01

    Background/Aims To evaluate the anticancer activity of fenbendazole, a widely used antihelminth with mechanisms of action that overlap with those of the hypoxia-selective nitroheterocyclic cytotoxins/radiosensitizers and the taxanes. Materials and Methods We used EMT6 mouse mammary tumor cells in cell culture and as solid tumors in mice to examine the cytotoxic and antitumor effects of fenbendazole as a single agent and in combination regimens. Results Intensive treatments with fenbendazole were toxic to EMT6 cells in vitro; toxicity increased with incubation time and under conditions of severe hypoxia. Fenbendazole did not alter the dose-response curves for radiation or docetaxel; instead, the agents produced additive cytotoxicities. Febendazole in maximally-intensive regimens did not alter the growth of EMT6 tumors, or increase the antineoplastic effects of radiation. Conclusion These studies provided no evidence that fenbendazole would have value in cancer therapy, but suggested that this general class of compounds merits further investigation. PMID:23393324

  8. Profiling the hydA gene and hydA gene transcript levels of Clostridium butyricum during continuous, mixed-culture hydrogen fermentation

    Energy Technology Data Exchange (ETDEWEB)

    Tolvanen, Katariina E.S.; Koskinen, Perttu E.P.; Santala, Ville P.; Karp, Matti T. [Department of Chemistry and Bioengineering, Tampere University of Technology, P.O. Box 541, FI-33101 Tampere (Finland); Raussi, Hanna-Mari; Ylikoski, Alice I.; Hemmilae, Ilkka A. [PerkinElmer Life Sciences, Wallac Oy, P.O. Box 10, FI-20101 Turku (Finland)

    2008-10-15

    The purpose of the research was to investigate the hydrogenase (hydA) gene and the corresponding transcript levels of Clostridium butyricum during continuous hydrogen fermentation. A quantitative real-time PCR (qrt-PCR) method was developed to specifically target the C. butyricum hydrogenase gene and mRNA in samples collected from a continuous, mixed-culture bioreactor over a period of 30 days (operation days 114-144). The detection limit of the qrt-PCR was 3.9 x 10{sup 2}hydA copies and the linear range 3.9 x 10{sup 2}-3.9 x 10{sup 7}hydA copies. The results showed that after a re-inoculation of the bioreactor on day 120 the hydA copy numbers started to rise and stabilized after day 127. The number of hydA transcript continued to rise until day 142. The results demonstrate that this method is suitable for detecting the hydA gene and gene transcript levels of C. butyricum from bioreactor samples. The expression level of hydA gene changed during continuous operation and can, therefore, be a useful target for process performance monitoring. (author)

  9. Heat Stress Regulates the Expression of Genes at Transcriptional and Post-Transcriptional Levels, Revealed by RNA-seq in Brachypodium distachyon

    Science.gov (United States)

    Chen, Shoukun; Li, Haifeng

    2017-01-01

    Heat stress greatly affects plant growth/development and influences the output of crops. With the increased occurrence of extreme high temperature, the negative influence on cereal products from heat stress becomes severer and severer. It is urgent to reveal the molecular mechanism in response to heat stress in plants. In this research, we used RNA-seq technology to identify differentially expressed genes (DEGs) in leaves of seedlings, leaves and inflorescences at heading stage of Brachypodium distachyon, one model plant of grasses. Results showed many genes in responding to heat stress. Of them, the expression level of 656 DEGs were altered in three groups of samples treated with high temperature. Gene ontology (GO) analysis showed that the highly enriched DEGs were responsible for heat stress and protein folding. According to KEGG pathway analysis, the DEGs were related mainly to photosynthesis-antenna proteins, the endoplasmic reticulum, and the spliceosome. Additionally, the expression level of 454 transcription factors belonging to 49 gene families was altered, as well as 1,973 splicing events occurred after treatment with high temperature. This research lays a foundation for characterizing the molecular mechanism of heat stress response and identifying key genes for those responses in plants. These findings also clearly show that heat stress regulates the expression of genes not only at transcriptional level, but also at post-transcriptional level. PMID:28119730

  10. 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

  11. Advances in chalcones with anticancer activities.

    Science.gov (United States)

    Karthikeyan, Chandrabose; Moorthy, Narayana S H Narayana; Ramasamy, Sakthivel; Vanam, Uma; Manivannan, Elangovan; Karunagaran, Devarajan; Trivedi, Piyush

    2015-01-01

    Chalcones are naturally occurring compounds exhibiting broad spectrum biological activities including anticancer activity through multiple mechanisms. Literature on anticancer chalcones highlights the employment of three pronged strategies, namely; structural manipulation of both aryl rings, replacement of aryl rings with heteroaryl scaffolds, molecular hybridization through conjugation with other pharmacologically interesting scaffolds for enhancement of anticancer properties. Methoxy substitutions on both the aryl rings (A and B) of the chalcones, depending upon their positions in the aryl rings appear to influence anticancer and other activities. Similarly, heterocyclic rings either as ring A or B in chalcones, also influence the anticancer activity shown by this class of compounds. Hybrid chalcones formulated by chemically linking chalcones to other prominent anticancer scaffolds such as pyrrol[2,1-c][1,4]benzodiazepines, benzothiazoles, imidazolones have demonstrated synergistic or additive pharmacological activities. The successful application of these three pronged strategies for discovering novel anticancer agents based on chalcone scaffold has resulted in many novel and chemically diverse chalcones with potential therapeutic application for many types of cancer. This review summarizes the concerted efforts expended on the design and development of anticancer chalcones recorded in recent literature and also provides an overview of the patents published in this area between 2007 and 2014 (WO2013022951, WO201201745 & US2012029489).

  12. 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

  13. The anticancer properties of phytochemical extracts from Salvia plants

    Directory of Open Access Journals (Sweden)

    Jiang YY

    2016-03-01

    Full Text Available Yuanyuan Jiang,1,2 Li Zhang,2 HP Vasantha Rupasinghe1,3 1Department of Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS, Canada; 2College of Science, Sichuan Agricultural University, Yaan, Sichuan, People's Republic of China; 3Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada Abstract: Salvia species have been used as traditional medicine in many countries for a long time for health benefits. More importantly, in recent decades, the extracts of Salvia species have been shown to exhibit significant anticancer effects in vitro and in vivo on a wide range of cancer types. Therefore, this review provides a systematic summary of the anticancer profile and the underlying mechanisms of the extracts from Salvia species, which reveals the potential of these species, especially Salvia miltiorrhiza and Salvia officinalis, to be used as natural anticancer agents or auxiliary agents and bring new insights for further research and development of the genus Salvia. Keywords: Salvia, chemoprevention, anticancer, phytochemicals, sage, Danshen

  14. Antidiabetic and anticancer activities of Mangifera indica cv. Okrong leaves

    Directory of Open Access Journals (Sweden)

    Aunyachulee Ganogpichayagrai

    2017-01-01

    Full Text Available Diabetes and cancer are a major global public health problem. Plant-derived agents with undesirable side-effects were required. This study aimed to evaluate antidiabetic and anticancer activities of the ethanolic leaf extract of Mangifera indica cv. Okrong and its active phytochemical compound, mangiferin. Antidiabetic activities against yeast α-glucosidase and rat intestinal α-glucosidase were determined using 1 mM of p-nitrophenyl-α-D-glucopyranoside as substrate. Inhibitory activity against porcine pancreatic α-amylase was performed using 1 mM of 2-chloro-4 nitrophenol-α-D-maltotroside-3 as substrate. Nitrophenol product was spectrophotometrically measured at 405 nm. Anticancer activity was evaluated against five human cancer cell lines compared to two human normal cell lines using 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay. Mango leaf extract and mangiferin exhibited dose-dependent inhibition against yeast α-glucosidase with the IC 50 of 0.0503 and 0.5813 mg/ml, respectively, against rat α-glucosidase with the IC 50 of 1.4528 and 0.4333 mg/ml, respectively, compared to acarbose with the IC 50 of 11.9285 and 0.4493 mg/ml, respectively. For anticancer activity, mango leaf extract, at ≥200 μg/ml showed cytotoxic potential against all tested cancer cell lines. In conclusion, mango leaf possessed antidiabetic and anticancer potential in vitro.

  15. Thiazide diuretics affect osteocalcin production in human osteoblasts at the transcription level without affecting vitamin D3 receptors.

    Science.gov (United States)

    Lajeunesse, D; Delalandre, A; Guggino, S E

    2000-05-01

    Besides their natriuretic and calciuretic effect, thiazide diuretics have been shown to decrease bone loss rate and improve bone mineral density. Clinical evidence suggests a specific role of thiazides on osteoblasts, because it reduces serum osteocalcin (OC), an osteoblast-specific protein, yet the mechanisms implicated are unknown. We therefore investigated the role of hydrochlorothiazide (HCTZ) on OC production by the human osteoblast-like cell line MG-63. HCTZ dose-dependently (1-100 microM) inhibited 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]-induced OC release by these cells (maximal effect, -40-50% and p ethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) only partly prevented the inhibitory effect of the diuretic on OC secretion (maximal effect, -22.5+/-6.9%), suggesting that thiazide-dependent Ca2+ influx is not sufficient to elicit the inhibition of OC secretion. Because OC production is strictly dependent on the presence of 1,25(OH)2D3 in human osteoblasts, we next evaluated the possible role of HCTZ on vitamin D3 receptors (VDR) at the mRNA and protein levels. Both Northern and Western blot analyses showed no effect of HCTZ (1-100 microM) on VDR levels. The presence of EGTA in the culture media reduced slightly the VDR mRNA levels under basal condition but this was not modified in the presence of increasing levels of HCTZ. The OC gene promoter also is under the control of transcription factors such as Yin Yang 1 (YY1) and cFOS. Western blot analysis revealed no changes in YY1 levels in response to HCTZ either in the presence or in the absence of 0.5 mM EGTA in the culture media. In contrast, HCTZ induced a dose-dependent increase in cFOS levels (p production by HCTZ could explain its preventive role in bone loss rate.

  16. Synergy and antagonism of active constituents of ADAPT-232 on transcriptional level of metabolic regulation of isolated neuroglial cells.

    OpenAIRE

    Alexander George Panossian; Rebecca eHamm; Onat eKadioglu; Georg Carl Wikman; Thomas eEfferth

    2013-01-01

    Gene expression profiling was performed on the human neuroglial cell line T98G after treatment with adaptogen ADAPT-232 and its constituents – extracts of Eleutherococcus senticosus root, Schisandra chinensis berry, and Rhodiola rosea root as well as several constituents individually, namely, eleutheroside E, schizandrin B, salidroside, triandrin, and tyrosol. A common feature for all tested adaptogens was their effect on G-protein-coupled receptor (GPCR) signaling pathways, i.e. cAMP, phosph...

  17. Synergy and Antagonism of Active Constituents of ADAPT-232 on Transcriptional Level of Metabolic Regulation of Isolated Neuroglial Cells

    OpenAIRE

    Panossian, Alexander; Hamm, Rebecca; Kadioglu, Onat; Wikman, Georg; Efferth, Thomas

    2013-01-01

    Gene expression profiling was performed on the human neuroglial cell line T98G after treatment with adaptogen ADAPT-232 and its constituents – extracts of Eleutherococcus senticosus root, Schisandra chinensis berry, and Rhodiola rosea root as well as several constituents individually, namely, eleutheroside E, schizandrin B, salidroside, triandrin, and tyrosol. A common feature for all tested adaptogens was their effect on G-protein-coupled receptor signaling pathways, i.e., cAMP, phospholipas...

  18. 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.

  19. 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

  20. Synergy and Antagonism of Active Constituents of ADAPT-232 on Transcriptional Level of Metabolic Regulation of Isolated Neuroglial Cells.

    Science.gov (United States)

    Panossian, Alexander; Hamm, Rebecca; Kadioglu, Onat; Wikman, Georg; Efferth, Thomas

    2013-01-01

    Gene expression profiling was performed on the human neuroglial cell line T98G after treatment with adaptogen ADAPT-232 and its constituents - extracts of Eleutherococcus senticosus root, Schisandra chinensis berry, and Rhodiola rosea root as well as several constituents individually, namely, eleutheroside E, schizandrin B, salidroside, triandrin, and tyrosol. A common feature for all tested adaptogens was their effect on G-protein-coupled receptor signaling pathways, i.e., cAMP, phospholipase C (PLC), and phosphatidylinositol signal transduction pathways. Adaptogens may reduce the cAMP level in brain cells by down-regulation of adenylate cyclase gene ADC2Y and up-regulation of phosphodiesterase gene PDE4D that is essential for energy homeostasis as well as for switching from catabolic to anabolic states and vice versa. Down-regulation of cAMP by adaptogens may decrease cAMP-dependent protein kinase A activity in various cells resulting in inhibition stress-induced catabolic transformations and saving of ATP for many ATP-dependant metabolic transformations. All tested adaptogens up-regulated the PLCB1 gene, which encodes phosphoinositide-specific PLC and phosphatidylinositol 3-kinases (PI3Ks), key players for the regulation of NF-κB-mediated defense responses. Other common targets of adaptogens included genes encoding ERα estrogen receptor (2.9-22.6 fold down-regulation), cholesterol ester transfer protein (5.1-10.6 fold down-regulation), heat shock protein Hsp70 (3.0-45.0 fold up-regulation), serpin peptidase inhibitor (neuroserpin), and 5-HT3 receptor of serotonin (2.2-6.6 fold down-regulation). These findings can be reconciled with the observed beneficial effects of adaptogens in behavioral, mental, and aging-associated disorders. Combining two or more active substances in one mixture significantly changes deregulated genes profiles: synergetic interactions result in activation of genes that none of the individual substances affected, while antagonistic

  1. 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.

  2. Peptides with Dual Antimicrobial and Anticancer Activities

    Science.gov (United States)

    Felício, Mário R.; Silva, Osmar N.; Gonçalves, Sônia; Santos, Nuno C.; Franco, Octávio L.

    2017-01-01

    In recent years, the number of people suffering from cancer and multi-resistant infections has increased, such that both diseases are already seen as current and future major causes of death. Moreover, chronic infections are one of the main causes of cancer, due to the instability in the immune system that allows cancer cells to proliferate. Likewise, the physical debility associated with cancer or with anticancer therapy itself often paves the way for opportunistic infections. It is urgent to develop new therapeutic methods, with higher efficiency and lower side effects. Antimicrobial peptides (AMPs) are found in the innate immune system of a wide range of organisms. Identified as the most promising alternative to conventional molecules used nowadays against infections, some of them have been shown to have dual activity, both as antimicrobial and anticancer peptides (ACPs). Highly cationic and amphipathic, they have demonstrated efficacy against both conditions, with the number of nature-driven or synthetically designed peptides increasing year by year. With similar properties, AMPs that can also act as ACPs are viewed as future chemotherapeutic drugs, with the advantage of low propensity to resistance, which started this paradigm in the pharmaceutical market. These peptides have already been described as molecules presenting killing mechanisms at the membrane level, but also acting toward intracellular targets, which increases their success compartively to one-target specific drugs. This review will approach the desirable characteristics of small peptides that demonstrated dual activity against microbial infections and cancer, as well as the peptides engaged in clinical trials. PMID:28271058

  3. 1,25-Dihydroxyvitamin D3 inhibits cytokine production by human blood monocytes at the post-transcriptional level

    DEFF Research Database (Denmark)

    Müller, K; Haahr, P M; Diamant, M

    1992-01-01

    (TNF-alpha), produced by the antigen presenting cells. In the present study we examined the effect of 1,25-(OH)2D3 on the production of these cytokines, as well as superoxide generation by freshly isolated mononuclear cells and partially purified monocytes. The immediate precursor of 1,25(OH)2D3, 25-OH...... D3, and the synthetic analogue MC 903 ('Calcipotriol') were examined in parallel. 1,25-(OH)2D3 dose-dependently inhibited the production of IL-alpha, IL-6 and TNF-alpha by Escherichia coli lipopolysaccharide (LPS)-stimulated monocytes, without affecting superoxide production. MC 903 had comparable......1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] inhibits lymphocyte proliferation and production of antibodies and lymphokines such as interleukin (IL)-2 and interferon gamma. These lymphocyte functions are dependent upon cytokines, including IL-1 alpha, IL-1 beta, IL-6 and tumour necrosis factor alpha...

  4. Synergy and antagonism of active constituents of ADAPT-232 on transcriptional level of metabolic regulation of isolated neuroglial cells.

    Directory of Open Access Journals (Sweden)

    Alexander George Panossian

    2013-02-01

    Full Text Available Gene expression profiling was performed on the human neuroglial cell line T98G after treatment with adaptogen ADAPT-232 and its constituents – extracts of Eleutherococcus senticosus root, Schisandra chinensis berry, and Rhodiola rosea root as well as several constituents individually, namely, eleutheroside E, schizandrin B, salidroside, triandrin, and tyrosol. A common feature for all tested adaptogens was their effect on G-protein-coupled receptor (GPCR signaling pathways, i.e. cAMP, phospholipase C and phosphatidylinositol signal transduction pathways. Adaptogens may reduce the cAMP level in brain cells by downregulation of adenylate cyclase gene ADC2Y and upregulation of phosphodiestherase gene PDE4D that is essential for energy homeostasis as well as for switching from catabolic to anabolic states and vice versa. All tested adaptogens up-regulated the PLCB1 gene, which encodes phosphoinositide-specific phospholipase C (PLC and phosphatidylinositol 3-kinases (PI3Ks, key players for the regulation of NF-B-mediated defense responses. Other common targets of adaptogens included genes encoding ERα estrogen receptor(2.9-22.6 fold down-regulation, cholesterol ester transfer protein (5.1-10.6 fold down-regulation, heat shock protein Hsp70 (3.0-45.0 fold up-regulation, serpin peptidase inhibitor (neuroserpin, and 5-HT3 receptor of serotonin (2.2-6.6 fold down-regulation. These findings can be reconciled with the observed beneficial effects of adaptogens in behavioral, mental and aging-associated disorders. Combining two or more active substances in one mixture significantly changes deregulated genes profiles: synergetic interactions result in activation of genes that none of the individual substances affected, while antagonistic interactions result in suppression some genes activated by individual substances. Merging of deregulated genes array profiles and intracellular networks is specific to the new substance with unique pharmacological

  5. Circadian rhythms and new options for novel anticancer therapies

    Directory of Open Access Journals (Sweden)

    Prosenc Zmrzljak U

    2015-01-01

    Full Text Available Ursula Prosenc ZmrzljakFaculty of Medicine, Center for Functional Genomics and Bio-Chips, Institute of Biochemistry, University of Ljubljana, Ljubljana, SloveniaAbstract: The patterns of activity/sleep, eating/fasting, etc show that our lives are under the control of an internal clock. Cancer is a systemic disease that affects sleep, feeding, and metabolism. All these processes are regulated by the circadian clock on the one hand, but on the other hand, they can serve as signals to tighten up the patient's circadian clock by robust daily routine. Usually, anticancer treatments take place in hospitals, where the patient's daily rest/activity pattern is changed. However, it has been shown that oncology patients with a disturbed circadian clock have poorer survival outcomes. The administration of different anticancer therapies can disturb the circadian cycle, but many cases show that circadian rhythms in tumors are deregulated per se. This fact can be used to plan anticancer therapies in such a manner that they will be most effective in antitumor action, but least toxic for the surrounding healthy tissue. Metabolic processes are highly regulated to prevent waste of energy and to ensure sufficient detoxification; as a consequence, xenobiotic metabolism is under tight circadian control. This gives the rationale for planning the administration of anticancer therapies in a chronomodulated manner. We review some of the potentially useful clinical praxes of anticancer therapies and discuss different possible approaches to be used in drug development and design in the future.Keywords: circadian rhythms, cancer, chronotherapy, detoxification metabolism

  6. Transcript levels of the Saccharomyes cerevisiae DNA repair gene RAD23 increase in response to UV light and in meiosis but remain constant in the mitotic cell cycle.

    Science.gov (United States)

    Madura, K; Prakash, S

    1990-08-25

    The RAD23 gene of Saccharomyces cerevisiae is required for excision-repair of UV damaged DNA. In this paper, we determine the location of the RAD23 gene in a cloned DNA fragment, identify the 1.6 kb RAD23 transcript, and examine RAD23 transcript levels in UV damaged cells, during the mitotic cell cycle, and in meiosis. The RAD23 mRNA levels are elevated 5-fold between 30 to 60 min after 37 J/m2 of UV light. RAD23 mRNA levels rise over 6-fold during meiosis at a stage coincident with high levels of genetic recombination. This response is specific to sporulation competent MATa/MAT alpha diploid cells, and is not observed in asporogenous MATa/MATa diploids. RAD23 mRNA levels, however, remain constant during the mitotic cell cycle.

  7. Transient increase in the transcript levels of gamma-tubulin complex genes during reorientation of cortical microtubules by gravity in azuki bean (Vigna angularis) epicotyls.

    Science.gov (United States)

    Soga, Kouichi; Kotake, Toshihisa; Wakabayashi, Kazuyuki; Kamisaka, Seiichiro; Hoson, Takayuki

    2008-09-01

    By hypergravity treatment, the percentage of cells with transverse microtubules was decreased, while that with longitudinal microtubules was increased in azuki bean (Vigna angularis) epicotyls. The expression of genes encoding gamma-tubulin complex (VaTUG and VaGCP3) was increased transiently in response to changes in the gravitational conditions. Lanthanum and gadolinium ions, potential blockers of mechanosensitive calcium ion-permeable channels (mechanoreceptors), nullified reorientation of microtubules as well as up-regulation of expression of VaTUG and VaGCP3 by hypergravity. These results suggest that mechanoreceptors may perceive the gravity signal, which leads to a transient increase in the transcript levels of gamma-tubulin complex genes and reorientation of cortical microtubules.

  8. 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.

  9. Retinoic acid regulates CD1d gene expression at the transcriptional level in human and rodent monocytic cells.

    Science.gov (United States)

    Chen, Qiuyan; Ross, A Catharine

    2007-04-01

    CD1d belongs to a group of nonclassical antigen-presenting molecules that present glycolipid antigens and thereby activate natural killer T (NKT) cells, a subset of bifunctional T cells. Little is known so far regarding the expression and physiologic regulation of CD1d. Here we show that all-trans-retinoic acid (RA), the active metabolite of vitamin A, rapidly (1 hr after treatment) increases CD1d mRNA in human and rodent monocytic cells at a physiologic dose (10 nM). The induction is RA specific and RA receptor (RAR) dependent-RA and an RARalpha agonist, Am580, both had a pronounced positive effect, whereas the addition of RARalpha antagonist partially blocked the increase in CD1d mRNA induced by RA and Am580. The induction was also completely blocked by the presence of actinomycin D. A putative RA-response element was identified in the distal 5' flanking region of the CD1d gene, which binds nuclear retinoid receptors and was responsive to RA in both gel mobility shift assay and transient transfection assay in THP-1 cells. These results further confirmed the transcriptional regulation of RA in CD1d gene expression. Moreover, RA significantly increased alpha-galactosylceramide-induced spleen cell proliferation. These studies together provide evidence for a previously unknown mechanism of CD1d gene expression regulation by RA and suggest that RA is a significant modulator of NKT cell activation.

  10. Comparison of cyanobacterial microcystin synthetase (mcy) E gene transcript levels, mcy E gene copies, and biomass as indicators of microcystin risk under laboratory and field conditions.

    Science.gov (United States)

    Ngwa, Felexce F; Madramootoo, Chandra A; Jabaji, Suha

    2014-08-01

    Increased incidences of mixed assemblages of microcystin-producing and nonproducing cyanobacterial strains in freshwater bodies necessitate development of reliable proxies for cyanotoxin risk assessment. Detection of microcystin biosynthetic genes in water blooms of cyanobacteria is generally indicative of the presence of potentially toxic cyanobacterial strains. Although much effort has been devoted toward elucidating the microcystin biosynthesis mechanisms in many cyanobacteria genera, little is known about the impacts of co-occurring cyanobacteria on cellular growth, mcy gene expression, or mcy gene copy distribution. The present study utilized conventional microscopy, qPCR assays, and enzyme-linked immunosorbent assay to study how competition between microcystin-producing Microcystis aeruginosa CPCC 299 and Planktothrix agardhii NIVA-CYA 126 impacts mcyE gene expression, mcyE gene copies, and microcystin concentration under controlled laboratory conditions. Furthermore, analyses of environmental water samples from the Missisquoi Bay, Quebec, enabled us to determine how the various potential toxigenic cyanobacterial biomass proxies correlated with cellular microcystin concentrations in a freshwater lake. Results from our laboratory study indicated significant downregulation of mcyE gene expression in mixed cultures of M. aeruginosa plus P. agardhii on most sampling days in agreement with depressed growth recorded in the mixed cultures, suggesting that interaction between the two species probably resulted in suppressed growth and mcyE gene expression in the mixed cultures. Furthermore, although mcyE gene copies and McyE transcripts were detected in all laboratory and field samples with measureable microcystin levels, only mcyE gene copies showed significant positive correlations (R(2) > 0.7) with microcystin concentrations, while McyE transcript levels did not. These results suggest that mcyE gene copies are better indicators of potential risks from microcystins

  11. PEGylation in anti-cancer therapy: An overview

    Directory of Open Access Journals (Sweden)

    Prajna Mishra

    2016-06-01

    Full Text Available 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 dramatically improves the pharmaceutical values; recent development of which includes fabrication of stimuli-sensitive polymers/smart polymers and polymeric micelles to cope of with the pathophysiological environment of targeted site with less toxic effects and more effectiveness. This overview discusses PEGylation involving proteins, enzymes, low molecular weight drugs, liposomes and nanoparticles that has been developed, clinically tried for anti-cancer therapy during the last decade.

  12. Moonlight affects nocturnal Period2 transcript levels in the pineal gland of the reef fish Siganus guttatus.

    Science.gov (United States)

    Sugama, Nozomi; Park, Ji-Gweon; Park, Yong-Ju; Takeuchi, Yuki; Kim, Se-Jae; Takemura, Akihiro

    2008-09-01

    The golden rabbitfish Siganus guttatus is a reef fish with a restricted lunar-synchronized spawning cycle. It is not known how the fish recognizes cues from the moon and exerts moon-related activities. In order to evaluate the perception and utilization of moonlight by the fish, the present study aimed to clone and characterize Period2 (Per2), a light-inducible clock gene in lower vertebrates, and to examine daily variations in rabbitfish Per2 (rfPer2) expression as well as the effect of light and moonlight on its expression in the pineal gland. The partially-cloned rfPer2 cDNA (2933 bp) was highly homologous (72%) to zebrafish Per2. The rfPer2 levels increased at ZT6 and decreased at ZT18 in the whole brain and several peripheral organs. The rfPer2 expression in the pineal gland exhibited a daily variation with an increase during daytime. Exposing the fish to light during nighttime resulted in a rapid increase of its expression in the pineal gland, while the level was decreased by intercepting light during daytime. Two hours after exposing the fish to moonlight at the full moon period, the rfPer2 expression was upregulated. These results suggest that rfPer2 is a light-inducible clock gene and that its expression is affected not only by daylight but also by moonlight. Since the rfPer2 expression level during the full moon period was higher than that during the new moon period, the monthly variation in the rfPer2 expression is likely to occur with the change in amplitude between the full and new moon periods.

  13. 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.

  14. Enhanced polyamine accumulation alters carotenoid metabolism at the transcriptional level in tomato fruit over-expressing spermidine synthase.

    Science.gov (United States)

    Neily, Mohamed Hichem; Matsukura, Chiaki; Maucourt, Mickaël; Bernillon, Stéphane; Deborde, Catherine; Moing, Annick; Yin, Yong-Gen; Saito, Takeshi; Mori, Kentaro; Asamizu, Erika; Rolin, Dominique; Moriguchi, Takaya; Ezura, Hiroshi

    2011-02-15

    Polyamines are involved in crucial plant physiological events, but their roles in fruit development remain unclear. We generated transgenic tomato plants that show a 1.5- to 2-fold increase in polyamine content by over-expressing the spermidine synthase gene, which encodes a key enzyme for polyamine biosynthesis. Pericarp-columella and placental tissue from transgenic tomato fruits were subjected to (1)H-nuclear magnetic resonance (NMR) for untargeted metabolic profiling and high-performance liquid chromatography-diode array detection for carotenoid profiling to determine the effects of high levels of polyamine accumulation on tomato fruit metabolism. A principal component analysis of the quantitative (1)H NMR data from immature green to red ripe fruit showed a clear discrimination between developmental stages, especially during ripening. Quantification of 37 metabolites in pericarp-columella and 41 metabolites in placenta tissues revealed distinct metabolic profiles between the wild type and transgenic lines, particularly at the late ripening stages. Notably, the transgenic tomato fruits also showed an increase in carotenoid accumulation, especially in lycopene (1.3- to 2.2-fold), and increased ethylene production (1.2- to 1.6-fold) compared to wild-type fruits. Genes responsible for lycopene biosynthesis, including phytoene synthase, phytoene desaturase, and deoxy-d-xylulose 5-phosphate synthase, were significantly up-regulated in ripe transgenic fruits, whereas genes involved in lycopene degradation, including lycopene-epsilon cyclase and lycopene beta cyclase, were down-regulated in the transgenic fruits compared to the wild type. These results suggest that a high level of accumulation of polyamines in the tomato regulates the steady-state level of transcription of genes responsible for the lycopene metabolic pathway, which results in a higher accumulation of lycopene in the fruit.

  15. Plant antimicrobial peptides as potential anticancer agents.

    Science.gov (United States)

    Guzmán-Rodríguez, Jaquelina Julia; Ochoa-Zarzosa, Alejandra; López-Gómez, Rodolfo; López-Meza, Joel E

    2015-01-01

    Antimicrobial peptides (AMPs) are part of the innate immune defense mechanism of many organisms and are promising candidates to treat infections caused by pathogenic bacteria to animals and humans. AMPs also display anticancer activities because of their ability to inactivate a wide range of cancer cells. Cancer remains a cause of high morbidity and mortality worldwide. Therefore, the development of methods for its control is desirable. Attractive alternatives include plant AMP thionins, defensins, and cyclotides, which have anticancer activities. Here, we provide an overview of plant AMPs anticancer activities, with an emphasis on their mode of action, their selectivity, and their efficacy.

  16. Single-stranded oligonucleotide adducts formed by Pt complexes favoring left-handed base canting: steric effect of flanking residues and relevance to DNA adducts formed by Pt anticancer drugs.

    Science.gov (United States)

    Saad, Jamil S; Marzilli, Patricia A; Intini, Francesco P; Natile, Giovanni; Marzilli, Luigi G

    2011-09-01

    Platinum anticancer drug binding to DNA creates large distortions in the cross-link (G*G*) and the adjacent XG* base pair (bp) steps (G* = N7-platinated G). These distortions, which are responsible for anticancer activity, depend on features of the duplex (e.g., base pairing) and of the cross-link moiety (e.g., the position and canting of the G* bases). The duplex structure stabilizes the head-to-head (HH) over the head-to-tail (HT) orientation and right-handed (R) over left-handed (L) canting of the G* bases. To provide fundamental chemical information relevant to the assessment of such duplex effects, we examine (S,R,R,S)-BipPt(oligo) adducts (Bip = 2,2'-bipiperidine with S,R,R,S chiral centers at the N, C, C, and N chelate ring atoms, respectively; oligo = d(G*pG*) with 3'- and/or 5'-substituents). The moderately bulky (S,R,R,S)-Bip ligand favors L canting and slows rotation about the Pt-G* bonds, and the (S,R,R,S)-BipPt(oligo) models provide more useful data than do dynamic models derived from active Pt drugs. All 5'-substituents in (S,R,R,S)-BipPt(oligo) adducts favor the normal HH conformer (∼97%) by destabilizing the HT conformer through clashes with the 3'-G* residue rather than through favorable H-bonding interactions with the carrier ligand in the HH conformer. For all (S,R,R,S)-BipPt(oligo) adducts, the S pucker of the 5'-X residue is retained. For these adducts, a 5'-substituent had only modest effects on the degree of L canting for the (S,R,R,S)-BipPt(oligo) HH conformer. This small flanking 5'-substituent effect on an L-canted HH conformer contrasts with the significant decrease in the degree of R canting previously observed for flanking 5'-substituents in the R-canted (R,S,S,R)-BipPt(oligo) analogues. The present data support our earlier hypothesis that the distortion distinctive to the XG* bp step (S to N pucker change and movement of the X residue) is required for normal stacking and X·X' WC H bonding and to prevent XG* residue clashes.

  17. 三氧化二砷纳米粒子对直肠癌作用的实验研究%Study on anticancer effect of arsenic trioxide nanoparticles on rectal cancer

    Institute of Scientific and Technical Information of China (English)

    梁桃; 陈颖颖; 薄挽澜

    2010-01-01

    目的 探讨三氧化二砷纳米粒子在体外、体内对直肠癌的抗癌作用.方法 Annexin V-FITC/PI染色流式细胞术检测三氧化二砷纳米粒子诱导直肠癌细胞HR8348凋亡情况;建立HR8348细胞裸鼠皮下移植瘤模型,监测给药后肿瘤体积的变化,并通过对肿瘤组织标本Ki67染色和TUNEL染色检测肿瘤细胞增殖和凋亡情况.结果 流式细胞术结果显示,4.0 μmol/L三氧化二砷纳米粒子诱导直肠癌细胞凋亡率为7.02%,高于对照组(1.76%),P<0.05,三氧化二砷纳米粒子体外可诱导直肠癌细胞的凋亡.在体内,三氧化二砷纳米粒子可抑制HR8348裸鼠皮下移植瘤的生长,4.0 μmol/L三氧化二砷纳米粒子组增殖指数(31.61%)低于对照组(66.75%),而凋亡指数(19.21%)高于对照组(6.47%),P<0.05.可抑制肿瘤细胞的增殖,诱导细胞凋亡.结论 在直肠癌中,三氧化二砷纳米粒子通过抑制增殖,诱导凋亡而发挥抗癌作用,是直肠癌治疗的良好药物.%Objective To investigate the anticancer effect of arsenic trioxide nanoparticles on rectal cancer in vitro and in vivo. Methods In cultured rectal cancer cells HR8348, flow cytometry were used to evaluate proliferation inhibitory and proapoptotic effect of arsenic trioxide nanoparticles; Rectal cancer xenograft model was established by s.c. injection of HR8348 cells into nude mice. The tumor volume was monitored after exposure to arsenic trioxide nanoparticles, Ki67 staining and TUNEL assay were used to assess tumor cell proliferation and apoptosis in tumor tissue. Results The data of flow cytometry indicate that cancer cell apoptosis induced by 4.0 μmol/L arsenic trioxide nanoparticles was 7.02%, higher than by control group ( 1.76% ),P <0.05. In vivo, arsenic trioxide nanoparticles can inhibit the growth of HR8348 nude mice. In the group of 4. 0 μmol/L arsenic trioxide nanoparticles ,proliferation index (31.61%) was lower than in the control group (66.75%), while the

  18. Salinomycin: a novel anti-cancer agent with known anti-coccidial activities.

    Science.gov (United States)

    Zhou, Shuang; Wang, Fengfei; Wong, Eric T; Fonkem, Ekokobe; Hsieh, Tze-Chen; Wu, Joseph M; Wu, Erxi

    2013-01-01

    Salinomycin, traditionally used as an anti-coccidial drug, has recently been shown to possess anti-cancer and anti-cancer stem cell (CSC) effects, as well as activities to overcome multi-drug resistance based on studies using human cancer cell lines, xenograft mice, and in case reports involving cancer patients in pilot clinical trials. Therefore, salinomycin may be considered as a promising novel anti-cancer agent despite its largely unknown mechanism of action. This review summarizes the pharmacologic effects of salinomycin and presents possible mechanisms by which salinomycin exerts its anti-tumorigenic activities. Recent advances and potential complications that might limit the utilization of salinomycin as an anti-cancer and anti-CSC agent are also presented and discussed.

  19. Tumor-targeted intracellular delivery of anticancer drugs through the mannose-6-phosphate/insulin-like growth factor II receptor

    NARCIS (Netherlands)

    Prakash, Jai; Beljaars, Leonie; Harapanahalli, Akshay K.; Zeinstra-Smith, Mieke; de Jager-Krikken, Alie; Hessing, Martin; Steen, Herman; Poelstra, Klaas

    2010-01-01

    Tumor-targeting of anticancer drugs is an interesting approach for the treatment of cancer since chemotherapies possess several adverse effects. In the present study, we propose a novel strategy to deliver anticancer drugs to the tumor cells through the mannose-6-phosphate/insulin-like growth factor

  20. 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.

  1. Anticancer Properties of Capsaicin Against Human Cancer.

    Science.gov (United States)

    Clark, Ruth; Lee, Seong-Ho

    2016-03-01

    There is persuasive epidemiological and experimental evidence that dietary phytochemicals have anticancer activity. Capsaicin is a bioactive phytochemical abundant in red and chili peppers. While the preponderance of the data strongly indicates significant anticancer benefits of capsaicin, more information to highlight molecular mechanisms of its action is required to improve our knowledge to be able to propose a potential therapeutic strategy for use of capsaicin against cancer. Capsaicin has been shown to alter the expression of several genes involved in cancer cell survival, growth arrest, angiogenesis and metastasis. Recently, many research groups, including ours, found that capsaicin targets multiple signaling pathways, oncogenes and tumor-suppressor genes in various types of cancer models. In this review article, we highlight multiple molecular targets responsible for the anticancer mechanism of capsaicin. In addition, we deal with the benefits of combinational use of capsaicin with other dietary or chemotherapeutic compounds, focusing on synergistic anticancer activities.

  2. Glutamic acid as anticancer agent: An overview.

    Science.gov (United States)

    Dutta, Satyajit; Ray, Supratim; Nagarajan, K

    2013-10-01

    The objective of the article is to highlight various roles of glutamic acid like endogenic anticancer agent, conjugates to anticancer agents, and derivatives of glutamic acid as possible anticancer agents. Besides these emphases are given especially for two endogenous derivatives of glutamic acid such as glutamine and glutamate. Glutamine is a derivative of glutamic acid and is formed in the body from glutamic acid and ammonia in an energy requiring reaction catalyzed by glutamine synthase. It also possesses anticancer activity. So the transportation and metabolism of glutamine are also discussed for better understanding the role of glutamic acid. Glutamates are the carboxylate anions and salts of glutamic acid. Here the roles of various enzymes required for the metabolism of glutamates are also discussed.

  3. Phytochemicals as Anticancer and Chemopreventive Topoisomerase II Poisons

    OpenAIRE

    2013-01-01

    Phytochemicals are a rich source of anticancer drugs and chemopreventive agents. Several of these chemicals appear to exert at least some of their effects through interactions with topoisomerase II, an essential enzyme that regulates DNA supercoiling and removes knots and tangles from the genome. Topoisomerase II-active phytochemicals function by stabilizing covalent protein-cleaved DNA complexes that are intermediates in the catalytic cycle of the enzyme. As a result, these compounds convert...

  4. New trends for metal complexes with anticancer activity

    OpenAIRE

    Bruijnincx, Pieter C A; Sadler, P. J.

    2008-01-01

    Medicinal inorganic chemistry can exploit the unique properties of metal ions for the design of new drugs. This has, for instance, led to the clinical application of chemotherapeutic agents for cancer treatment, such as cisplatin. The use of cisplatin is, however, severely limited by its toxic side effects. This has spurred chemists to employ different strategies in the development of new metal-based anticancer agents with different mechanisms of action. Recent trends in the field are discuss...

  5. Evaluating the anticancer potential of ethanolic gall extract of Terminalia chebula (Gaertn. Retz. (combretaceae

    Directory of Open Access Journals (Sweden)

    B E Ravi Shankara

    2016-01-01

    The present investigation establishes the anticancer activities of T. chebula leaf gall extracts on BRL3A, MCF-.7, and A-.549 cells. Presumably, these activities could be attributed in part to the phenolics/flavanoids features of the extract that has been demonstrated to act as cytotoxic agents. The experimental evidence obtained in the laboratory model could provide a rationale for the traditional use of plant as a source of easily available effective anticancer agents to the people, particularly in developing countries.

  6. Evolution in Medicinal Chemistry of Ursolic Acid Derivatives as Anticancer Agents

    OpenAIRE

    Chen, Haijun; Gao, Yu; Wang, Ailan; Zhou, Xiaobin; Zheng, Yunquan; Zhou, Jia

    2015-01-01

    Currently, there is a renewed interest in common dietaries and plant-based traditional medicines for the prevention and treatment of cancer. In the search for potential anticancer agents from natural sources, ursolic acid (UA), a pentacyclic triterpenoid widely found in various medicinal herbs and fruits, exhibits powerful biological effects including its attractive anticancer activity against various types of cancer cells. However, the limited solubility, rapid metabolism and poor bioavailab...

  7. Serendipity in anticancer drug discovery.

    Science.gov (United States)

    Hargrave-Thomas, Emily; Yu, Bo; Reynisson, Jóhannes

    2012-01-10

    It was found that the discovery of 5.8% (84/1437) of all drugs on the market involved serendipity. Of these drugs, 31 (2.2%) were discovered following an incident in the laboratory and 53 (3.7%) were discovered in a clinical setting. In addition, 263 (18.3%) of the pharmaceuticals in clinical use today are chemical derivatives of the drugs discovered with the aid of serendipity. Therefore, in total, 24.1% (347/1437) of marketed drugs can be directly traced to serendipitous events confirming the importance of this elusive phenomenon. In the case of anticancer drugs, 35.2% (31/88) can be attributed to a serendipitous event, which is somewhat larger than for all drugs. The therapeutic field that has benefited the most from serendipity are central nervous system active drugs reflecting the difficulty in designing compounds to pass the blood-brain-barrier and the lack of laboratory-based assays for many of the diseases of the mind.

  8. 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.

  9. Potential anti-cancer drugs commonly used for other indications.

    Science.gov (United States)

    Hanusova, Veronika; Skalova, Lenka; Kralova, Vera; Matouskova, Petra

    2015-01-01

    An increasing resistance of mammalian tumor cells to chemotherapy along with the severe side effects of commonly used cytostatics has raised the urgency in the search for new anti-cancer agents. Several drugs originally approved for indications other than cancer treatment have recently been found to have a cytostatic effect on cancer cells. These drugs could be expediently repurposed as anti-cancer agents, since they have already been tested for toxicity in humans and animals. The groups of newly recognized potential cytostatics discussed in this review include benzimidazole anthelmintics (albendazole, mebendazole, flubendazole), anti-hypertensive drugs (doxazosin, propranolol), psychopharmaceuticals (chlorpromazine, clomipramine) and antidiabetic drugs (metformin, pioglitazone). All these drugs have a definite potential to be used especially in combinations with other cytostatics; the chemotherapy targeting of multiple sites now represents a promising approach in cancer treatment. The present review summarizes recent information about the anti-cancer effects of selected drugs commonly used for other medical indications. Our aim is not to collect all the reported results, but to present an overview of various possibilities. Advantages, disadvantages and further perspectives regarding individual drugs are discussed and evaluated.

  10. A study of the potential anticancer activity of Mangifera zeylanica bark: Evaluation of cytotoxic and apoptotic effects of the hexane extract and bioassay-guided fractionation to identify phytochemical constituents.

    Science.gov (United States)

    Ediriweera, Meran Keshawa; Tennekoon, Kamani Hemamala; Samarakoon, Sameera Ranganath; Thabrew, Ira; Dilip DE Silva, Egodage

    2016-02-01

    The present study investigated the potential anticancer activity of the bark of Mangifera zeylanica, an endemic plant in Sri Lanka that has been traditionally used for cancer therapy. Cytotoxic and apoptotic effects were investigated in vitro using sulphorodamine assay, acridine orange and ethidium bromide staining, caspase-3 and -7 activity, DNA fragmentation and reverse transcription-quantitative polymerase chain reaction in estrogen receptor positive MCF-7 and triple-negative MDA-MB-231 breast cancer cell lines, SKOV-3 ovarian cancer cell line and MCF-10A normal mammary epithelial cells. Hexane extract demonstrated increased levels of cytotoxicity in cancer cells (IC50, 86.6-116.5 µg/ml) compared with normal cells (IC50, 217.2 µg/ml). Chloroform extract demonstrated increased cytotoxicity to normal cells (IC50, 92.9 µg/ml) compared with cancer cells (IC50, 280.1-506.5 µg/ml). Exposure to the hexane extract led to morphological changes characteristic of apoptosis and DNA fragmentation in the three cancer cell lines. Caspase-3 and -7 were significantly activated in MDA-MB-231 and SKOV-3 cells, indicating the occurrence of caspase-dependent apoptosis in these cells, and caspase-independent apoptosis in MCF-7 cells. Furthermore, upregulation of proapoptotic Bcl-2-associated X protein occurred in the three cancer cell lines, and antiapoptotic survivin was downregulated in MCF-7 and SKOV-3 cells; by contrast, tumor protein p53 was upregulated only in MCF-7 cells, suggesting p53-mediated apoptosis in MCF-7 cells and p53-independent apoptosis in the remaining cancerous cell lines. In addition, fraction M1 obtained from bioactivity-guided fractionation of the hexane extract demonstrated increased cytotoxicity in cancer cells (IC50, 15.4-38.7 µg/ml) compared with normal cells (IC50, 114.6 µg/ml), with the highest cytotoxicity observed in MDA-MB-231 triple-negative breast cancer cells. The hexane extract of M. zeylanica bark contained polyphenols and flavonoids, and

  11. 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.

  12. 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.

  13. Novel antimicrobial peptides with high anticancer activity and selectivity.

    Directory of Open Access Journals (Sweden)

    Hung-Lun Chu

    Full Text Available We describe a strategy to boost anticancer activity and reduce normal cell toxicity of short antimicrobial peptides by adding positive charge amino acids and non-nature bulky amino acid β-naphthylalanine residues to their termini. Among the designed peptides, K4R2-Nal2-S1 displayed better salt resistance and less toxicity to hRBCs and human fibroblast than Nal2-S1 and K6-Nal2-S1. Fluorescence microscopic studies indicated that the FITC-labeled K4R2-Nal2-S1 preferentially binds cancer cells and causes apoptotic cell death. Moreover, a significant inhibition in human lung tumor growth was observed in the xenograft mice treated with K4R2-Nal2-S1. Our strategy provides new opportunities in the development of highly effective and selective antimicrobial and anticancer peptide-based therapeutics.

  14. Human-derived normal mesenchymal stem/stromal cells in anticancer therapies

    Science.gov (United States)

    Zhang, Cheng; Yang, Shi-Jie; Wen, Qin; Zhong, Jiang F; Chen, Xue-Lian; Stucky, Andres; Press, Michael F; Zhang, Xi

    2017-01-01

    The tumor microenvironment (TME) not only plays a pivotal role during cancer progression and metastasis, but also has profound effects on therapeutic efficacy. Stromal cells of the TME are increasingly becoming a key consideration in the development of active anticancer therapeutics. However, dispute concerning the role of stromal cells to fight cancer continues because the use of mesenchymal stem/stromal cells (MSCs) as an anticancer agent is dependent on the specific MSCs subtype, in vitro or in vivo conditions, factors secreted by MSCs, types of cancer cell lines and interactions between MSCs, cancer cells and host immune cells. In this review, we mainly focus on the role of human-derived normal MSCs in anticancer therapies. We first discuss the use of different MSCs in the therapies for various cancers. We then focus on their anticancer mechanism and clinical application. PMID:28123601

  15. Anticancer Activity of Polyether Ionophore-Salinomycin.

    Science.gov (United States)

    Antoszczak, Michał; Huczyński, Adam

    2015-01-01

    Since the discovery of unusual anti-tumor activity of natural polyether antibiotic - Salinomycin, this compound, along with its derivatives, has been intensively studied against different human cancer cells, both in vivo and in vitro. Salinomycin has shown strong inhibition activity against the proliferation process of many different cancer cells, including multi-drug resistance (MDR) cancer cells, as well as cancer stem cells (CSCs), i.e. leukemic stem cells, colon carcinoma stem cells, prostate cancer stem cells and many others. Additionally, the application of Salinomycin has been proved to enhance the anti-cancer effect of radio- and chemotherapy. Preliminary clinical studies have shown tumor regression and only transient acute side effects after application of Salinomycin. Up to now, major efforts have been devoted to elucidate the biological mechanisms of anti-tumor activity of Salinomycin and it is expected that the results may provide new therapeutic strategies based on biological modulation of Salinomycin activity. This review is focused on and describes the possible role of Salinomycin in cancer therapy and gives an overview of its properties.

  16. Macrocyclic trichothecenes as antifungal and anticancer compounds.

    Science.gov (United States)

    de Carvalho, Maira Peres; Weich, Herbert; Abraham, Wolf-Rainer

    2016-01-01

    Trichothecenes are sesquiterpenoid metabolites produced by fungi and species of the plant genus Baccharis, family Asteraceae. They comprise a tricyclic core with an epoxide at C-12 and C-13 and can be grouped into non-macrocyclic and macrocyclic compounds. While many of these compounds are of concern in agriculture, the macrocyclic metabolites have been evaluated as antiviral, anti-cancer, antimalarial and antifungal compounds. Some known cytotoxic responses on eukaryotic cells include inhibition of protein, DNA and RNA syntheses, interference with mitochondrial function, effects on cell division and membranes. These targets however have been elucidated essentially employing non-macrocyclic trichothecenes and only one or two closely related macrocyclic compounds. For several macrocyclic trichothecenes high selectivity against fungal species and against cancer cell lines have been reported suggesting that the macrocycle and its stereochemistry are of crucial importance regarding biological activity and selectivity. This review is focused on compounds belonging to the macrocyclic type, where a cyclic diester or triester ring binds to the trichothecane moiety at C-4 and C- 15 leading to natural products belonging to the groups of satratoxins, verrucarins, roridins, myrotoxins and baccharinoids. Their biological activities, cytotoxic mechanisms and structure-activity relationships (SAR) are discussed. From the reported data it becomes evident that even small changes in the molecules can lead to pronounced effects on biological activity or selectivity against cancer cells lines. Understanding the underlying mechanisms may help to design highly specific drugs for cancer therapy.

  17. 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.

  18. 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.

  19. Phenethyl isothiocyanate: a comprehensive review of anti-cancer mechanisms.

    Science.gov (United States)

    Gupta, Parul; Wright, Stephen E; Kim, Sung-Hoon; Srivastava, Sanjay K

    2014-12-01

    The epidemiological evidence suggests a strong inverse relationship between dietary intake of cruciferous vegetables and the incidence of cancer. Among other constituents of cruciferous vegetables, isothiocyanates (ITC) are the main bioactive chemicals present. Phenethyl isothiocyanate (PEITC) is present as gluconasturtiin in many cruciferous vegetables with remarkable anti-cancer effects. PEITC is known to not only prevent the initiation phase of carcinogenesis process but also to inhibit the progression of tumorigenesis. PEITC targets multiple proteins to suppress various cancer-promoting mechanisms such as cell proliferation, progression and metastasis. Pre-clinical evidence suggests that combination of PEITC with conventional anti-cancer agents is also highly effective in improving overall efficacy. Based on accumulating evidence, PEITC appears to be a promising agent for cancer therapy and is already under clinical trials for leukemia and lung cancer. This is the first review which provides a comprehensive analysis of known targets and mechanisms along with a critical evaluation of PEITC as a future anti-cancer agent.

  20. Liposome Delivery Systems for Inhalation: A Critical Review Highlighting Formulation Issues and Anticancer Applications.

    Science.gov (United States)

    Rudokas, Mindaugas; Najlah, Mohammad; Alhnan, Mohamed Albed; Elhissi, Abdelbary

    2016-01-01

    This is a critical review on research conducted in the field of pulmonary delivery of liposomes. Issues relating to the mechanism of nebulisation and liposome composition were appraised and correlated with literature reports of liposome formulations used in clinical trials to understand the role of liposome size and composition on therapeutic outcome. A major highlight was liposome inhalation for the treatment of lung cancers. Many in vivo studies that explored the potential of liposomes as anticancer carrier systems were evaluated, including animal studies and clinical trials. Liposomes can entrap anticancer drugs and localise their action in the lung following pulmonary delivery. The safety of inhaled liposomes incorporating anticancer drugs depends on the anticancer agent used and the amount of drug delivered to the target cancer in the lung. The difficulty of efficient targeting of liposomal anticancer aerosols to the cancerous tissues within the lung may result in low doses reaching the target site. Overall, following the success of liposomes as inhalable carriers in the treatment of lung infections, it is expected that more focus from research and development will be given to designing inhalable liposome carriers for the treatment of other lung diseases, including pulmonary cancers. The successful development of anticancer liposomes for inhalation may depend on the future development of effective aerosolisation devices and better targeted liposomes to maximise the benefit of therapy and reduce the potential for local and systemic adverse effects.

  1. Self-compatibility in 'Cristobalina' sweet cherry is not associated with duplications or modified transcription levels of S-locus genes.

    Science.gov (United States)

    Wünsch, A; Tao, R; Hormaza, J I

    2010-07-01

    Sweet cherry shows S-RNase-based gametophytic self-incompatibility, which prevents self- and cross-fertilization between genetically related individuals. The specificity of the self-incompatible reaction is determined by two genes located in the S-locus. These encode a pistil-expressed ribonuclease (S-RNase) that inhibits self pollen tube growth, and a pollen-expressed F-box protein (SFB) that may be involved in the cytotoxicity of self-S-RNases. Initial genetic and pollination studies in a self-compatible sweet cherry cultivar, 'Cristobalina' (S (3) S (6)), showed that self-compatibility was caused by the loss of pollen function of both haplotypes (S (3) and S (6)). In this study, we further characterize self-compatibility in this genotype by molecular analysis of the S-locus. DNA blot analyses using S-RNase and SFB probes show no duplications of 'Cristobalina' S-locus genes or differences in the restriction patterns when compared with self-incompatible cultivars with the same S-genotype. Furthermore, reverse transcriptase-PCR of S-locus genes and quantitative reverse transcription-PCR of SFBs revealed no differences at the transcription level when compared with a self-incompatible genotype. The results of this study show that no differences at the S-locus can be correlated with self-compatibility, indicating the possible involvement of non-S-locus modifiers in self-incompatibility breakdown in this cultivar.

  2. 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.

  3. PARP1 promotes gene expression at the post-transcriptional level by modulating the RNA-binding protein HuR

    Science.gov (United States)

    Ke, Yueshuang; Han, Yanlong; Guo, Xiaolan; Wen, Jitao; Wang, Ke; Jiang, Xue; Tian, Xue; Ba, Xueqing; Boldogh, Istvan; Zeng, Xianlu

    2017-01-01

    Poly(ADP-ribosyl)ation (PARylation) is mainly catalysed by poly-ADP-ribose polymerase 1 (PARP1), whose role in gene transcription modulation has been well established. Here we show that, in response to LPS exposure, PARP1 interacts with the adenylateuridylate-rich element-binding protein embryonic lethal abnormal vision-like 1 (Elavl1)/human antigen R (HuR), resulting in its PARylation, primarily at site D226. PARP inhibition and the D226 mutation impair HuR's PARylation, nucleocytoplasmic shuttling and mRNA binding. Increases in mRNA level or stability of pro-inflammatory cytokines/chemokines are abolished by PARP1 ablation or inhibition, or blocked in D226A HuR-expressing cells. The present study demonstrates a mechanism to regulate gene expression at the post-transcriptional level, and suggests that blocking the interaction of PARP1 with HuR could be a strategy to treat inflammation-related diseases that involve increased mRNA stability. PMID:28272405

  4. 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.

  5. Calcium channel as a potential anticancer agent.

    Science.gov (United States)

    Kriazhev, L

    2009-11-01

    Anticancer treatment in modern clinical practices includes chemotherapy and radiation therapy with or without surgical interventions. Efficiency of both methods varies greatly depending on cancer types and stages. Besides, chemo- and radiotherapy are toxic and damaging that causes serious side effects. This fact prompts the search for alternative methods of antitumor therapy. It is well known that prolonged or high increase of intracellular calcium concentration inevitably leads to the cell death via apoptosis or necrosis. However, stimulation of cell calcium level by chemical agents is hardly achievable because cells have very sophisticated machinery for maintaining intracellular calcium in physiological ranges. This obstacle can be overridden, nevertheless. It was found that calcium channels in so called calcium cells in land snails are directly regulated by extracellular calcium concentration. The higher the concentration the higher the calcium intake is through the channels. Bearing in mind that extracellular/intracellular calcium concentration ratio in human beings is 10,000-12,000 fold the insertion of the channel into cancer cells would lead to fast and uncontrollable by the cells calcium intake and cell death. Proteins composing the channel may be extracted from plasma membrane of calcium cells and sequenced by mass-spectrometry or N-terminal sequencing. Either proteins or corresponding genes could be used for targeted delivery into cancer cells.

  6. 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.

  7. In silico prediction of anticancer peptides by TRAINER tool

    Directory of Open Access Journals (Sweden)

    Zohre Hajisharifi

    2013-03-01

    Full Text Available Cancer is one of the causes of death in the world. Several treatment methods exist against cancer cells such as radiotherapy and chemotherapy. Since traditional methods have side effects on normal cells and are expensive, identification and developing a new method to cancer therapy is very important. Antimicrobial peptides, present in a wide variety of organisms, such as plants, amphibians and mammals, are newly discovered agents. These peptides have various structures, sizes and molecular compositions; hence developing a computational method to predict these anticancer peptides is useful. In the present study, first, 2 databases with 138 and 206 anticancer and non-anticancer peptides were introduced, classified by TRAINER. TRAINER (http://www.baskent.edu.tr/~hogul/ TRAINER/ is a new online tool designed for classification of any alphabet of sequences. TRAINER allows users to select from among several feature representation schemes and supervised machine learning methods with relevant parameters. In this study, Naive Bayes and radial basis were used in a support vector machine. The accuracy and specificity in combination of features by Naive Bayes were 83% and by radial basis 87% and 92% respectively. The results demonstrate that two methods are useful for classification of these peptides; however, the accuracy of Radial Basis is higher than Naive Bayes.

  8. In silico prediction of anticancer peptides by TRAINER tool

    Directory of Open Access Journals (Sweden)

    Zohre Hajisharifi

    2013-06-01

    Full Text Available Cancer is one of the causes of death in the world. Several treatment methods exist against cancer cells such as radiotherapy and chemotherapy. Since traditional methods have side effects on normal cells and are expensive, identification and developing a new method to cancer therapy is very important. Antimicrobial peptides, present in a wide variety of organisms, such as plants, amphibians and mammals, are newly discovered agents. These peptides have various structures, sizes and molecular compositions; hence developing a computational method to predict these anticancer peptides is useful. In the present study, first, 2 databases with 138 and 206 anticancer and non-anticancer peptides were introduced, classified by TRAINER. TRAINER (http://www.baskent.edu.tr/~hogul/ TRAINER/ is a new online tool designed for classification of any alphabet of sequences. TRAINER allows users to select from among several feature representation schemes and supervised machine learning methods with relevant parameters. In this study, Naive Bayes and radial basis were used in a support vector machine. The accuracy and specificity in combination of features by Naive Bayes were 83% and by radial basis 87% and 92% respectively. The results demonstrate that two methods are useful for classification of these peptides; however, the accuracy of Radial Basis is higher than Naive Bayes.

  9. Anticancer efficacy of unique pyridine-based tetraindoles.

    Science.gov (United States)

    Fu, Chih-Wei; Hsieh, Yun-Jung; Chang, Tzu Ting; Chen, Chia-Ling; Yang, Cheng-Yu; Liao, Anne; Hsiao, Pei-Wen; Li, Wen-Shan

    2015-11-02

    Results of previous studies demonstrated that the tetraindole, SK228, which has a high lipid but low water solubility, displayed moderate anticancer efficacy in a xenograft model of breast cancer. This finding led to the proposal that new, pyridine based tetraindole (PBT) analogs of SK228, containing tetraindole moieties distributed about central protonated pyridine cores, would have enhanced bioavailabilities and anticancer efficacies. Among the PBTs prepared and subjected to biological studies, 3f (FCW81) was observed to display the highest antiproliferative activity against the two triple negative breast cancer (TNBCs) cell lines, MDA-MB-231 and BT549. In addition, its mode of action was shown to involve G2/M arrest of the cell cycle along with the promotion of increased levels of cyclin B1 and p-chk2 and a decreased level of p-cdc2. DNA damage and induction of apoptosis caused by FCW81 was found to be associated with a decrease in DNA repair. Significantly, FCW81 displays therapeutic efficacy in a xenograft model of human breast cancer by not only serving to inhibit markedly the growth of cancer cells but also to block effectively cancer cell metastasis. Collectively, the results of these studies have led to the identification of novel pyridine-tetraindole based anticancer agents with potential use in TNBC therapy.

  10. 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.

  11. Murine breast carcinoma 4T1 cells are more sensitive to atranorin than normal epithelial NMuMG cells in vitro: Anticancer and hepatoprotective effects of atranorin in vivo.

    Science.gov (United States)

    Solár, Peter; Hrčková, Gabriela; Koptašíková, Lenka; Velebný, Samuel; Solárová, Zuzana; Bačkor, Martin

    2016-04-25

    The aim of this study was to evaluate the anticancer effect of atranorin (ATR) on murine 4T1 breast carcinoma cells and compare its sensitivity with normal mammary epithelial NMuMG cells in vitro. Anti-tumor and hepatoprotective activity of ATR-therapy was examined on mouse model of 4T1-induced cancer disease. ATR significantly reduced clonogenic ability of carcinoma 4T1 cells at the concentration of 75 μM, but clonogenicity of normal NMuMG cells was not affected by any of ATR concentrations tested. Moreover, flow cytometric and BrdU incorporation analysis did not confirm the inhibited entry into S-phase of the cell cyle after ATR incubation, and on the contrary, it induced apoptosis associated with the activation of caspase-3 and PARP cleavage in 4T1 cells. Although ATR did not cause any significant changes in Bcl-xL protein expression in NMuMG cells, an apparent depletion of Bcl-xL protein in 4T1 cells after 48 h ATR therapy was confirmed. Based on this result as well as the result of the total cell number decline, we can conclude that 4T1 cells are more sensitive to ATR therapy than NMuMG cells. ATR administration resulted in significantly longer survival time of BALB/c mice inoculated with 4T1 cells, what was associated with reduced tumor size and the higher numbers of apoptotic 4T1 cells. No differences were recorded in the number of BrdU-positive tumor cells between ATR-treated group and controls. Results indicate that ATR has rather proapoptotic than antiproliferative effect on 4T1 cells in vitro and in vivo and normal NMuMG cells are less sensitive to ATR. Furthermore, our studies revealed protective effect of ATR against oxidative stress in the livers of the tumor-bearing mice.

  12. 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.

  13. Anticancer Properties of Phyllanthus emblica (Indian Gooseberry).

    Science.gov (United States)

    Zhao, Tiejun; Sun, Qiang; Marques, Maud; Witcher, Michael

    2015-01-01

    There is a wealth of information emanating from both in vitro and in vivo studies indicating fruit extract of the Phyllanthus emblica tree, commonly referred to as Indian Gooseberries, has potent anticancer properties. The bioactivity in this extract is thought to be principally mediated by polyphenols, especially tannins and flavonoids. It remains unclear how polyphenols from Phyllanthus emblica can incorporate both cancer-preventative and antitumor properties. The antioxidant function of Phyllanthus emblica can account for some of the anticancer activity, but clearly other mechanisms are equally important. Herein, we provide a brief overview of the evidence supporting anticancer activity of Indian Gooseberry extracts, suggest possible mechanisms for these actions, and provide future directions that might be taken to translate these findings clinically.

  14. Anticancer Properties of Phyllanthus emblica (Indian Gooseberry

    Directory of Open Access Journals (Sweden)

    Tiejun Zhao

    2015-01-01

    Full Text Available There is a wealth of information emanating from both in vitro and in vivo studies indicating fruit extract of the Phyllanthus emblica tree, commonly referred to as Indian Gooseberries, has potent anticancer properties. The bioactivity in this extract is thought to be principally mediated by polyphenols, especially tannins and flavonoids. It remains unclear how polyphenols from Phyllanthus emblica can incorporate both cancer-preventative and antitumor properties. The antioxidant function of Phyllanthus emblica can account for some of the anticancer activity, but clearly other mechanisms are equally important. Herein, we provide a brief overview of the evidence supporting anticancer activity of Indian Gooseberry extracts, suggest possible mechanisms for these actions, and provide future directions that might be taken to translate these findings clinically.

  15. Development of an LC-MS/MS assay for the quantitative determination of the intracellular 5-fluorouracil nucleotides responsible for the anticancer effect of 5-fluorouracil

    NARCIS (Netherlands)

    Derissen, Ellen J B; Hillebrand, Michel J X; Rosing, Hilde; Schellens, Jan H M; Beijnen, Jos H.

    2015-01-01

    5-Fluorouracil (5-FU) and its oral prodrug capecitabine are among the most widely used chemotherapeutics. For cytotoxic activity, 5-FU requires cellular uptake and intracellular metabolic activation. Three intracellular formed metabolites are responsible for the antineoplastic effect of 5-FU: 5-fluo

  16. Parental somatic and germ-line mosaicism for a FBN2 mutation and analysis of FBN2 transcript levels in dermal fibroblasts.

    Science.gov (United States)

    Putnam, E A; Park, E S; Aalfs, C M; Hennekam, R C; Milewicz, D M

    1997-01-01

    Congenital contractural arachnodactyly (CCA) is an autosomal dominant disorder that is phenotypically related to the Marfan syndrome. CCA has recently been shown to result from mutations in the FBN2 gene, which encodes an elastin-associated microfibrillar protein called fibrillin-2. Two siblings are reported here with classic manifestations of CCA with unaffected parents. Analysis of the FBN2 cDNA from dermal fibroblasts from one of the affected siblings revealed a heterozygous exon splicing error deleting nt 3722-3844 of the FBN2 mRNA. This cDNA deletion resulted in selective removal of one of the 43 calcium-binding EGF-like domains of the fibrillin-2 protein. Analysis of the FBN2 gene in the affected siblings' DNA indicated that the splicing error resulted from an A-to-G transition 15 nt upstream from the 3' splice site of the intron. The genomic mutation resulting in the splicing error alters a putative branch point sequence important for lariat formation, an intermediate structure of normal splicing. The mutation was detectable in DNA from the father's hair bulbs and buccal cells but not his white blood cell DNA, indicating that the father was a somatic mosaic. Analysis of transcript levels by use of dermal fibroblasts from the proband demonstrated that the FBN2 allele containing the exon deletion was expressed at a higher level than the allele inherited from the mother. These results indicate that FBN2 exon splicing errors are a cause of CCA, furthering the understanding of the molecular basis of this disorder. In addition, the demonstration of gonadal mosaicism in the FBN2 gene is important for accurate genetic counseling of families with sporadic cases of CCA. Finally, the preferential expression of the mutated FBN2 allele in dermal fibroblasts may have implications for understanding the pathogenesis and rarity of CCA. Images Figure 1 Figure 3 Figure 4 PMID:9106527

  17. Early host responses to avian influenza A virus are prolonged and enhanced at transcriptional level depending on maturation of the immune system.

    Science.gov (United States)

    Reemers, Sylvia S; van Leenen, Dik; Koerkamp, Marian J Groot; van Haarlem, Daphne; van de Haar, Peter; van Eden, Willem; Vervelde, Lonneke

    2010-05-01

    Newly hatched chickens are more susceptible to infectious diseases than older birds because of an immature immune system. The aim of this study was to determine to what extent host responses to avian influenza virus (AIV) inoculation are affected by age. Therefore, 1- and 4-week (wk) old birds were inoculated with H9N2 AIV or saline. The trachea and lung were sampled at 0, 8, 16 and 24h post-inoculation (h.p.i.) and gene expression profiles determined using microarray analysis. Firstly, saline controls of both groups were compared to analyse the changes in gene profiles related to development. In 1-wk-old birds, higher expression of genes related to development of the respiratory immune system and innate responses were found, whereas in 4-wk-old birds genes were up regulated that relate to the presence of higher numbers of leukocytes in the respiratory tract. After inoculation with H9N2, gene expression was most affected at 16 h.p.i. in 1-wk-old birds and at 16 and 24h.p.i. in 4-wk-old birds in the trachea and especially in the lung. In 1-wk-old birds less immune related genes including innate related genes were induced which might be due to age-dependent reduced functionality of antigen presenting cells (APC), T cells and NK cells. In contrast cytokine and chemokines gene expression was related to viral load in 1-wk-old birds and less in 4-wk-old birds. Expression of cellular host factors that block virus replication by interacting with viral factors was independent of age or tissue for most host factors. These data show that differences in development are reflected in gene expression and suggest that the strength of host responses at transcriptional level may be a key factor in age-dependent susceptibility to infection, and the cellular host factors involved in virus replication are not.

  18. 洋葱挥发油抗肿瘤作用的实验研究%Anticancer Effect of Volatile Oil Extracts of Allium cepa

    Institute of Scientific and Technical Information of China (English)

    方阅; 刘皋林; 张渊

    2011-01-01

    目的:研究洋葱挥发油离体对人肝癌细胞株(QCY-7703)、人胃癌细胞株(MGC-803)、人宫颈癌细胞株(Hela)、人肺腺癌细胞株(SPC-A-1)的增殖抑制作用和在体对小鼠肉瘤S180及小鼠艾氏腹水癌的抑制作用.方法:采用MTT法检测不同剂量的洋葱挥发油对4种肿瘤细胞增殖的影响,复制小鼠肉瘤S180和小鼠艾氏腹水癌模型,检测不同剂量(1000、500、250 mg·kg-1)的洋葱挥发油对小鼠肿瘤的抑制作用,比较其抑制率.结果:洋葱挥发油离体和在体实验中对肿瘤细胞均具有较强的增殖抑制作用.结论:洋葱挥发油能抑制多种肿瘤细胞的增殖,对肿瘤细胞有明显的细胞毒性作用.%OBJECTIVE:To study the in vitro inhibition effect of volatile oil extracts of A11ium cepa on the proliferation of QCY-7703, MGC-803, Hela, SPC-A-1 cells and the in vivo inhibition effect on sarcoma S180 and Ehrlich ascites carcinoma in mice. METHODS: MTT assay was used to detect the effect of volatile oil extracts of A. cepa with different dose on the proliferation of 4 kinds of tumor cells. We established sarcoma S180 and ehrlich ascites carcinoma model, detected the inhibition effect of volatile oil extracts of A. cepa with different dose on tumor and compared their inhibition rate. RESULTS: Volatile oil extracts of A.cepa have the distinct in vitro and in vivo inhibition effect on the proliferation of tumor cells. CONCLUSION: Volatile oil extracts of A. cepa can inhibit the proliferation of variety of tumor cells, and it has cytotoxic effect on tumor cells.

  19. 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.

  20. Magnetic polymer nanospheres for anticancer drug targeting

    Energy Technology Data Exchange (ETDEWEB)

    JurIkova, A; Csach, K; Koneracka, M; Zavisova, V; Tomasovicova, N; Lancz, G; Kopcansky, P; Timko, M; Miskuf, J [Institute of Experimental Physics, Slovak Academy of Sciences, 040 01 Kosice (Slovakia); Muckova, M, E-mail: akasard@saske.s [Hameln rds a.s., 900 01 Modra (Slovakia)

    2010-01-01

    Poly(D,L-lactide-co-glycolide) polymer (PLGA) nanospheres loaded with biocom-patible magnetic fluid as a magnetic carrier and anticancer drug Taxol were prepared by the modified nanoprecipitation method with size of 200-250 nm in diameter. The PLGA polymer was utilized as a capsulation material due to its biodegradability and biocompatibility. Taxol as an important anticancer drug was chosen for its significant role against a wide range of tumours. Thermal properties of the drug-polymer system were characterized using thermal analysis methods. It was determined the solubility of Taxol in PLGA nanospheres. Magnetic properties investigated using SQUID magnetometry showed superparamagnetism of the prepared magnetic polymer nanospheres.

  1. The ellagic acid-derived gut microbiota metabolite, urolithin A, potentiates the anticancer effects of 5-fluorouracil chemotherapy on human colon cancer cells.

    Science.gov (United States)

    González-Sarrías, Antonio; Tomé-Carneiro, Joao; Bellesia, Andrea; Tomás-Barberán, Francisco A; Espín, Juan Carlos

    2015-05-01

    Chemotherapy increases the overall survival in colorectal cancer (CRC) patients. 5-Fluorouracil (5-FU) remains as a drug of first choice in CRC therapy over the last four decades. However, only 10-15% of patients with advanced CRC respond positively to 5-FU monotherapy. Therefore, new strategies to enhance the 5-FU effectiveness, overcome the tumor cell resistance and decrease the unspecific toxicity are critically needed. Urolithin A (Uro-A) is the main metabolite produced by the human gut microbiota from the dietary polyphenol ellagic acid. Uro-A targets the colonic mucosa of CRC patients, and preclinical studies have shown the anti-inflammatory and cancer chemopreventive activities of this metabolite. We evaluated here whether Uro-A, at concentrations achievable in the human colorectum, could sensitize colon cancer cells to 5-FU and 5'DFUR (a pro-drug intermediate of 5-FU). We found that both 5-FU and 5'DFUR arrested the cell cycle at the S phase by regulating cyclins A and B1 in the human colon cancer cells Caco-2, SW-480 and HT-29, and also triggered apoptosis through the activation of caspases 8 and 9. Co-treatments with Uro-A decreased IC50 values for both 5-FU and 5'DFUR and additionally arrested the cell cycle at the G2/M phase together with a slight increase in caspases 8 and 9 activation. Overall, we show that Uro-A potentiated the effects of both 5-FU and 5'DFUR on colon cancer cells. This suggests the need for lower 5-FU doses to achieve similar effects, which could reduce possible adverse effects. Further in vivo investigations are warranted to explore the possible role of Uro-A as a chemotherapy adjuvant.

  2. Anti-cancer Effect and Underlying Mechanism(s) of Kaempferol, a Phytoestrogen, on the Regulation of Apoptosis in Diverse Cancer Cell Models.

    Science.gov (United States)

    Kim, Seung-Hee; Choi, Kyung-Chul

    2013-12-31

    Phytoestrogens exist in edible compounds commonly found in fruits or plants. For long times, phytoestrogens have been used for therapeutic treatments against human diseases, and they can be promising ingredients for future pharmacological industries. Kaempferol is a yellow compound found in grapes, broccoli and yellow fruits, which is one of flavonoid as phytoestrogens. Kaempferol has been suggested to have an antioxidant and anti-inflammatory effect. In past decades, many studies have been performed to examine anti-toxicological role(s) of kaempferol against human cancers. It has been shown that kaempferol may be involved in the regulations of cell cycle, metastasis, angiogenesis and apoptosis in various cancer cell types. Among them, there have been a few of the studies to examine a relationship between kaempferol and apoptosis. Thus, in this review, we highlight the effect(s) of kaempferol on the regulation of apoptosis in diverse cancer cell models. This could be a forecast in regard to use of kaempferol as promising treatment against human diseases.

  3. Antifungal and anticancer effects of a polysaccharide-protein complex from the gut bacterium Raoultella ornithinolytica isolated from the earthworm Dendrobaena veneta.

    Science.gov (United States)

    Fiołka, Marta J; Lewtak, Kinga; Rzymowska, Jolanta; Grzywnowicz, Krzysztof; Hułas-Stasiak, Monika; Sofińska-Chmiel, Weronika; Skrzypiec, Krzysztof

    2013-06-21

    The polysaccharide-protein complex (PPC) isolated from metabolites of gut bacteria Raoultella ornithinolytica from Dendrobaena veneta earthworms exhibits activity against Candida albicans, in breast ductal carcinoma (line T47D) and in the endometrioid ovarian cancer line (TOV-112D) in vitro. The action against C. albicans was analyzed using light, SEM, TEM, and AFM microscopes. The changes observed indicated two directions of the action of the complex, that is, disturbance of metabolic activity and cell wall damage. The PPC is an adhesion-promoting complex inducing death of C. albicans cells by necrosis. Owing to its significant effect on C. albicans, the complex is a promising source of antifungal compounds. The PPC showed a minimal cytotoxic effect against human skin fibroblasts; however, the cytotoxicity against the T47D line was determined at 20% and 15% against the TOV-112D line. The action of the PPC against the T47D line exerted a cytopathic effect, whereas in the TOV-112D line, it caused a reduction in the cell number. The PPC induced death of tumor cells by apoptosis and necrosis. In view of the negligible cytotoxicity on fibroblasts, the PPC will be subjected to chemical modifications to increase its antitumor activity for prospective medical applications.

  4. Caryophyllene oxide exhibits anti-cancer effects in MG-63 human osteosarcoma cells via the inhibition of cell migration, generation of reactive oxygen species and induction of apoptosis

    Directory of Open Access Journals (Sweden)

    Zheng Pan

    2016-12-01

    Full Text Available The main objective of the present study was to evaluate the antitumor and apoptotic effects of caryophyllene oxide in MG-63 human osteosarcoma cells. Cell viability of these cells was evaluated by MTT assay while as in vitro wound healing assay was used to study the effect of caryophyllene oxide on cell migration. Fluorescence microscopy and transmission electron microscopy were used to study the changes in cell morphology once the cells undergo apoptosis. Caryophyllene oxide significantly led to cytotoxicity in MG-63 cells showing dose-dependent as well as time-dependent effects. Caryophyllene oxide led to an inhibition of wound closure significantly. At caryophyllene oxide doses of 20, 80 and 120 µM, the percentage of cell migration was shown to be 94.2, 67.1 and 14.8% respectively. With an increase in the caryophyllene oxide dose, the extent of apoptosis also increased characterized by cellular shrinkage, membrane blebbing, chromatin condensation and apoptotic body formation.

  5. Anti-cancer effects of 2-oxoquinoline derivatives on the HCT116 and LoVo human colon cancer cell lines.

    Science.gov (United States)

    Fang, Feng-Qi; Guo, Hui-Shu; Zhang, Jie; Ban, Li-Ying; Liu, Ji-Wei; Yu, Pei-Yao

    2015-12-01

    The present study demonstrated the anti-tumor effects of the quinoline derivative [5-(3-chloro-oxo-4-phenyl-cyclobutyl)-quinoli-8-yl-oxy] acetic acid hydrazide (CQAH) against colorectal carcinoma. Substantial apoptotic effects of CQAH on HCT116 and LoVo human colon cancer cell lines were observed. Apoptosis was identified based on cell morphological characteristics, including cell shrinkage and chromatin condensation as well as Annexin V/propidium iodide double staining followed by flow cytometric analysis and detection of apoptosis-associated proteins by western blot analysis. CQAH induced caspase-3 and PARP cleavage, reduced the expression of the anti-apoptotic proteins myeloid cell leukemia-1 and B-cell lymphoma (Bcl) extra large protein and elevated the expression of the pro-apoptotic protein Bcl-2 homologous antagonist killer. In addition, pharmacological inhibition of c-Jun N-terminal kinase (JNK), but not extracellular signal-regulated kinase or p38, significantly reduced CQAH-mediated cell death as well as cleavage of caspase-3 and PARP. Co-treatment of CQAH with the commercial chemotherapeutics 5-fluorouracil and camptothecin-11 significantly improved their efficacies. Comparison of the apoptotic effects of CQAH with those of two illustrated structure-activity associations for this compound type, indicating that substitution at position-4 of the azetidine phenyl ring is pivotal for inducing apoptosis. In conclusion, the results of the present study indicated CQAH and its analogues are potent candidate drugs for the treatment of colon carcinoma.

  6. 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.

  7. Pro-inflammatory effect of a traditional Chinese medicine formula with potent anti-cancer activity in vitro impedes tumor inhibitory potential in vivo

    Science.gov (United States)

    Xia, Lei; Plachynta, Maksym; Liu, Tangjingjun; Xiao, Xiao; Song, Jialei; Li, Xiaogang; Zhang, Mu; Yao, Yao; Luo, Heng; Hao, Xiaojiang; Ben-David, Yaacov

    2016-01-01

    Medicinal formulas are a part of the complex discipline of traditional Chinese medicine that has been used for centuries in China and East Asia. These formulas predominantly consist of the extracts isolated from herbal plants, animal parts and medicinal minerals. The present study aimed to investigate the impact of 150 formulas, used as non-prescription drugs in China, on the treatment of cancer. A formula was identified, C54, commonly used to treat sore throats, which exhibited marked growth inhibition in vitro, associated with cell cycle arrest and apoptosis. Cytotoxicity was, in part, due to the ability of C54 to inhibit the expression and function of the transcription factor, Fli-1, leading to marked inhibition of leukemic cell growth in tissue culture. However, when injected into a model of leukemia initiated by Fli-1 activation, C54 only exhibited a limited tumor inhibition. C54 also did not suppress xenograft growth of the breast cancer cell line, MDA-MB-231, orthopedically transplanted into the mammary fat pad of severe combined immunodeficiency (SCID) mice. Notably, splenomegaly and accumulation of inflammatory CD11b+/Gr1+ monocytes were observed in the tumors and spleens of C54-treated mice. As inflammation is known to accelerate tumor progression, this immune response may counteract the cell-autonomous effect of C54, and account for its limited tumor inhibitory effect in vivo. Combining C54 with an anti-inflammatory drug may improve the potency of C54 for treatment of certain cancers. The present study has highlighted the complexity of Chinese medicinal compounds and the need to thoroughly analyze their systemic effects at high concentrations in vivo.

  8. Enhancing Anticancer Effect of Gefitinib across the Blood-Brain Barrier Model Using Liposomes Modified with One α-Helical Cell-Penetrating Peptide or Glutathione and Tween 80.

    Science.gov (United States)

    Lin, Kuan-Hung; Hong, Shu-Ting; Wang, Hsiang-Tsui; Lo, Yu-Li; Lin, Anya Maan-Yuh; Yang, James Chih-Hsin

    2016-11-29

    Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), such as gefitinib, have been demonstrated to effectively treat the patients of extracranial non-small cell lung cancer (NSCLC). However, these patients often develop brain metastasis (BM) during their disease course. The major obstacle to treat BM is the limited penetration of anticancer drugs across the blood-brain barrier (BBB). In the present study, we utilized gefitinib-loaded liposomes with different modifications to improve gefitinib delivery across the in vitro BBB model of bEnd.3 cells. Gefitinib was encapsulated in small unilamellar liposomes modified with glutathione (GSH) and Tween 80 (SUV-G+T; one ligand plus one surfactant) or RF (SUV-RF; one α-helical cell-penetrating peptide). GSH, Tween 80, and RF were tested by the sulforhodamine B (SRB) assay to find their non-cytotoxic concentrations on bEnd.3 cells. The enhancement on gefitinib across the BBB was evaluated by cytotoxicity assay on human lung adenocarcinoma PC9 cells under the bEnd.3 cells grown on the transwell inserts. Our findings showed that gefitinib incorporated in SUV-G+T or SUV-RF across the bEnd.3 cells significantly reduced the viability of PC9 cells more than that of free gefitinib. Furthermore, SUV-RF showed no cytotoxicity on bEnd.3 cells and did not affect the transendothelial electrical resistance (TEER) and transendothelial permeability of sodium fluorescein across the BBB model. Moreover, flow cytometry and confocal laser scanning microscopy were employed to evaluate the endocytosis pathways of SUV-RF. The results indicated that the uptake into bEnd.3 cells was mainly through adsorptive-mediated mechanism via electrostatic interaction and partially through clathrin-mediated endocytosis. In conclusion, cell penetrating peptide-conjugated SUV-RF shed light on improving drug transport across the BBB via modulating the transcytosis pathway(s).

  9. 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.

  10. 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.

  11. Epigenetic Activity of Peroxisome Proliferator-Activated Receptor Gamma Agonists Increases the Anticancer Effect of Histone Deacetylase Inhibitors on Multiple Myeloma Cells.

    Directory of Open Access Journals (Sweden)

    Nassera Aouali

    Full Text Available Epigenetic modifications play a major role in the development of multiple myeloma. We have previously reported that the PPARγ agonist pioglitazone (PIO enhances, in-vitro, the cytotoxic effect of the Histone deacetylase inhibitor (HDACi, valproic acid (VPA, on multiple myeloma cells. Here, we described the development of a new multiple myeloma mouse model using MOLP8 cells, in order to evaluate the effect of VPA/PIO combination on the progression of myeloma cells, by analyzing the proliferation of bone marrow plasma cells. We showed that VPA/PIO delays the progression of the disease and the invasion of myeloma cells in the bone marrow. Mechanistically, we demonstrated that VPA/PIO increases the cleavage of caspase 3 and PARP, and induces the acetylation of Histone 3 (H3. Furthermore, we provided evidence that PPARγ agonist is able to enhance the action of other HDACi such as Vorinostat or Mocetinostat. Using PPARγ antagonist or siPPARγ, we strongly suggest that, as described during adipogenesis, PIO behaves as an epigenetic regulator by improving the activity of HDACi. This study highlights the therapeutic benefit of PIO/VPA combination, compared to VPA treatment as a single-arm therapy on multiple myeloma and further highlights that such combination may constitute a new promising treatment strategy which should be supported by clinical trials.

  12. Anticancer effect of lupeol, a triterpene%三萜类化合物羽扇豆醇的抗肿瘤作用

    Institute of Scientific and Technical Information of China (English)

    张琳; 张有成

    2012-01-01

    Lupeol,a triterpene,is found in various edible and medicinal plants.Lupeol has been shown to exhibit strong anti-inflammatory,anti-arthritic,gene mutation prevention and anti-malarial effect.Recently,it is found that lupeol is the main active ingredients of inhibiting the growth of a several kinds of cancers and carcinomas in some antineoplastic plants.Lupeol has antineoplastic effect.%羽扇豆醇是从可食用植物和中草药中提取出来的一种新型三萜类成分.体内外研究证明,羽扇豆醇具有较强的抗炎、抗关节炎、抗基因突变和抗疟疾的作用.羽扇豆醇是某些抗癌植物抑制肿瘤的主要有效成分,近年来的研究提示羽扇豆醇具有抗癌作用.

  13. Ethanol extract of Artemisia sieversiana exhibits anticancer effects and induces apoptosis through a mitochondrial pathway involving DNA damage in COLO-205 colon carcinoma cells

    Directory of Open Access Journals (Sweden)

    Jun Tang

    2015-08-01

    Full Text Available The aim of the study was to see the antiproliferative and apoptotic effects of ethanolic herbal extract of Artemisia sieversiana against three human colon cancer (HT-29, HCT-15 and COLO-205 cells. The cytotoxicity of the extract on these cell lines was evaluated by MTT assay. Phase contrast and fluorescence microscopy using acridine orange/ethidium bromide (AO/ETBR staining was employed to investigate morphological alterations in COLO-205 cells by the herbal extract. Flow cytometry instrument measured the changes in mitochondrial membrane potential loss while as gel electrophoresis measured DNA damage in these cells. The extract at increasing doses exhibited a strong cytotoxic effect in a dose-dependent manner against all the three colon cancer cell lines. The IC50 values of the extract against HT-29, HCT-15 and COLO-205 cancer cells were found to be 52.1, 43.2 and 38.6 µg/mL respectively. Mitochondrial membrane potential loss (ΔΨm and DNA fragmentation events were also observed following extract treatment at increasing doses.

  14. Synthesis of (-)-arctigenin derivatives and their anticancer activity.

    Science.gov (United States)

    Gui-Rong, Chen; Li-Ping, Cai; De-Qiang, Dou; Ting-Guo, Kang; Hong-Fu, Li; Fu-Rui, Li; Ning, Jiang

    2012-01-01

    The natural dibenzylbutyrolactone type lignanolide (-)-arctigenin, which was prepared from fructus arctii, showed obvious anticancer activity. The synthesis of four new (-)-arctigenin derivatives and their anticancer bioactivities were examined. The structures of the four new synthetic derivatives were elucidated.

  15. Beer and selenium anticancer effect in mice with tumor%啤酒及硒对荷瘤小鼠的抗氧化作用

    Institute of Scientific and Technical Information of China (English)

    苏军; 陈金; 许秀举

    2011-01-01

    目的:探讨金川保健啤酒、啤酒加硒及硒对荷瘤小鼠的抗氧化作用。方法:用硒、啤酒及啤酒加硒饲养小鼠,通过测定血清丙二醛(MDA)、肝匀浆超氧化物歧化酶(SOD)及乳酸脱氢酶(LDH)来判定啤酒、啤酒加硒及硒对荷瘤小鼠的抗氧化作用。结果:啤酒组、啤酒加硒组及硒组荷瘤小鼠丙二醛(MDA)和乳酸脱氢酶(LDH)明显小于对照组,而超氧化物歧化酶(SOD)明显大于对照组。结论:金川保健啤酒、啤酒加硒及硒对荷瘤小鼠均有明显的抗氧化作用,并能降低其体内乳酸脱氢酶。%Objective: To study the antioxidant effect of selenium, jinchuan health beer and the combination of selenium and beer in mice with tumor. Methods: the mice were fed with selenium, beer and the combination of selenium and beer, we decided antioxidant effect by determining the serum malondialdehyde(MDA), liver superoxide dismutase(SOD), lactate dehydrogenase(LDH). Results: the serum malondialdehyde(MDA) and lactate dehydrogenase(LDH) in Se group, beer group and the combination of selenium and beer group were significantly lower than those of the control group(P〈0.05), The liver superoxide dismutase(SOD) in group Se, beer and the combination of selenium and beer was higher than that of the control group(P〈0.01). Conclusion: Selenium, beer and the combination of selenium and beer shows good antioxidant effect, reduce the lactate dehydrogenase(LDH) in vivo.

  16. 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.

  17. Early prediction of anticancer effects with diffusion-weighted MR imaging in patients with colorectal liver metastases following selective internal radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Dudeck, Oliver; Zeile, Martin; Wybranski, Christian; Schulmeister, Alice; Fischbach, Frank; Pech, Maciej; Wieners, Gero; Ruehl, Ricarda; Grosser, Oliver; Amthauer, Holger; Ricke, Jens [University of Magdeburg, Department of Radiology and Nuclear Medicine, Magdeburg (Germany)

    2010-11-15

    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.)

  18. 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

  19. Curcumin AntiCancer Studies in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Sabrina Bimonte

    2016-07-01

    Full Text Available 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.

  20. Methods for predicting anti-cancer response

    DEFF Research Database (Denmark)

    2013-01-01

    The present invention relates to methods for predicting response of a cancer in a subject to anti-cancer therapies based upon a determination and analysis of a chromosomal aberration score, such as the number of allelic imbalance or the number of telomeric allelic imbalance in the chromosomes...

  1. The aurora kinase inhibitor VX-680 shows anti-cancer effects in primary metastatic cells and the SW13 cell line.

    Science.gov (United States)

    Pezzani, Raffaele; Rubin, Beatrice; Bertazza, Loris; Redaelli, Marco; Barollo, Susi; Monticelli, Halenya; Baldini, Enke; Mian, Caterina; Mucignat, Carla; Scaroni, Carla; Mantero, Franco; Ulisse, Salvatore; Iacobone, Maurizio; Boscaro, Marco

    2016-10-01

    New therapeutic targets are needed to fight cancer. Aurora kinases (AK) were recently identified as vital key regulators of cell mitosis and have consequently been investigated as therapeutic targets in preclinical and clinical studies. Aurora kinase inhibitors (AKI) have been studied in many cancer types, but their potential capacity to limit or delay metastases has rarely been considered, and never in adrenal tissue. Given the lack of an effective pharmacological therapy for adrenal metastasis and adrenocortical carcinoma, we assessed AKI (VX-680, SNS314, ZM447439) in 2 cell lines (H295R and SW13 cells), 3 cell cultures of primary adrenocortical metastases (from lung cancer), and 4 primary adrenocortical tumor cell cultures. We also tested reversan, which is a P-gp inhibitor (a fundamental efflux pump that can extrude drugs), and we measured AK expression levels in 66 adrenocortical tumor tissue samples. Biomolecular and cellular tests were performed (such as MTT, thymidine assay, Wright's staining, cell cycle and apoptosis analysis, Western blot, qRT-PCR, and mutation analysis). Our results are the first to document AK overexpression in adrenocortical carcinoma as well as in H295R and SW13 cell lines, thus proving the efficacy of AKI against adrenal metastases and in the SW13 cancer cell model. We also demonstrated that reversan and AKI Vx-680 are useless in the H295R cell model, and therefore should not be considered as potential treatments for ACC. Serine/threonine AK inhibition, essentially with VX-680, could be a promising, specific therapeutic tool for eradicating metastases in adrenocortical tissue.

  2. 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.

  3. Recent developments of C-4 substituted coumarin derivatives as anticancer agents.

    Science.gov (United States)

    Dandriyal, Jyoti; Singla, Ramit; Kumar, Manvendra; Jaitak, Vikas

    2016-08-25

    Cancer is a prominent cause of death in global. Currently, the numbers of drugs that are in clinical practice are having a high prevalence of side effect and multidrug resistance. Researchers have made an attempt to expand a suitable anticancer drug that has no MDR and side effect. Coumarin scaffold became an attractive subject due to their broad spectrum of pharmacological activities. Coumarin derivatives extensively explored for anticancer activities as it possesses minimum side effect along with multi-drug reversal activity. Coumarin derivatives can act by various mechanisms on different tumor cell lines depending on substitution pattern of the core structure of coumarin. Substitution on coumarin nucleus leads to the search for more potent compounds. In this review, we have made an effort to give a synthetic strategy for the preparation of C-4 substituted coumarin derivatives as anticancer agents based on their mechanism of action and also discuss the SAR of the most active compound.

  4. 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

  5. A conserved region in the 3' untranslated region of the human LIMK1 gene is critical for proper expression of LIMK1 at the post-transcriptional level

    Institute of Scientific and Technical Information of China (English)

    Guang-Fei Deng; Shu-Jing Liu; Xun-Sha Sun; Wei-Wen Sun; Qi-Hua Zhao; Wei-Ping Liao; Yong-Hong Yi

    2013-01-01

    LIM kinase 1 (LIMK1),a cytosolic serine/threonine kinase,regulates actin filament dynamics and reorganization and is involved in neuronal development and brain function.Abnormal expression of LIMK1 is associated with several neurological disorders.In this study,we performed a conservation analysis using Vector NTI (8.0) software.The dualluciferase reporter assay and real-time quantitative RT-PCR were used to assess the protein and mRNA levels of the reporter gene,respectively.We found that a region ranging from nt +884 to +966 in the human LIMK1 3' untranslated region (UTR) was highly conserved in the mouse Limk1 3' UTR and formed a structure containing several loops and stems.Luciferase assay showed that the relative luciferase activity of the mutated construct with the conserved region deleted,pGL4-hLIMK1-3U-M,in SH-SY5Y and HEK-293 cells was only ~60% of that of the wild-type construct pGL4-hLIMK1-3U,indicating that the conserved region is critical for the reporter gene expression.Real-time quantitative RT-PCR analysis demonstrated that the relative Luc2 mRNA levels in SH-SY5Y and HEK293 cells transfected with pGL4-hLIMK1-3U-M decreased to ~50% of that in cells transfected with pGL4-hLIMK1-3U,suggesting an important role of the conserved region in maintaining Luc2 mRNA stability.Our study suggests that the conserved region in the LIMK1 3' UTR is involved in regulating LIMK1 expression at the post-transcriptional level,which may help reveal the mechanism underlying the regulation of LIMK1 expression in the central nervous system and explore the relationship between the 3'-UTR mutant and neurological disorders.

  6. 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.

  7. [Anticancer properties of Trichoderma asperellum 302 from buried soils].

    Science.gov (United States)

    Tukhbatova, R I; Fattakhova, A N; Alimova, F K

    2014-01-01

    Melanoma is one of the most malignant tumors, which leaves no chance of survival in the case of the "bang". There are various ways to treat tumors, however, recently in the field of cancer research, there are studies in which fungal metabolites have been used as antitumor agents. In this study we examined the effect of the culture fluid of the fungus Trichoderma asperellum 302 on the growth and development of melanoma B 16. We have shown that these culture fluid has anticancer properties, causing destruction of tumor tissue. Obtained data open new possibilities and prospects for the use of active substances derived from fungi in the complex therapy of cancer.

  8. 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.

  9. A Theoretical Model for the Hormetic Dose-response Curve for Anticancer Agents.

    Science.gov (United States)

    Yoshimasu, Tatsuya; Ohashi, Takuya; Oura, Shoji; Kokawa, Yozo; Kawago, Mitsumasa; Hirai, Yoshimitsu; Miyasaka, Miwako; Nishiguchi, Haruka; Kawashima, Sayoko; Yata, Yumi; Honda, Mariko; Fujimoto, Takahiro; Okamura, Yoshitaka

    2015-11-01

    In the present article, we quantitatively evaluated the dose-response relationship of hormetic reactions of anticancer agents in vitro. Serial dilutions of gemcitabine, cisplatin, 5-fluorouracil, vinorelbine, and paclitaxel were administered to the A549 non-small-cell lung cancer cell line. The bi-phasic sigmoidal curve with hormetic and cytotoxic effects is given by the formula y=(a-b/(1+exp(c(*)log(x)-d)))/(1+exp(e(*)log(x)-f)), that was used to perform a non-linear least square regression. The dose-responses of the five anticancer agents were fitted to this equation. Gemcitabine and 5-fluorouracil, which had the lowest ED50 for their hormetic reaction, had the most pronounced promotive effects out of the five anticancer agents tested. The hormetic reaction progressed exponentially with culturing time. Our theoretical model will be useful in predicting how hormetic reactions affect patients with malignant tumors.

  10. Oxadiazoles as privileged motifs for promising anticancer leads: recent advances and future prospects.

    Science.gov (United States)

    Khan, Imtiaz; Ibrar, Aliya; Abbas, Naeem

    2014-01-01

    Taking into account the rising trend of the incidence of cancers of various organs, effective therapies are urgently needed to control human malignancies. The rapid emergence of hundreds of new agents that modulate an ever-growing list of cancer-specific molecular targets offers tremendous hope for cancer patients. However, almost all of the chemotherapy drugs currently on the market cause serious side effects. Based on these facts, the design of new chemical entities as anticancer agents requires the simulation of a suitable bioactive pharmacophore. The pharmacophore not only should have the required potency but must also be safer on normal cell lines than on tumor cells. In this perspective, oxadiazole scaffolds with well-defined anticancer activity profile have fueled intense academic and industrial research in recent years. This paper is intended to highlight the recent advances along with current developments as well as future outlooks for the design of novel and efficacious anticancer agents based on oxadiazole motifs.

  11. Glutamic acid and its derivatives: candidates for rational design of anticancer drugs.

    Science.gov (United States)

    Ali, Imran; Wani, Waseem A; Haque, Ashanul; Saleem, Kishwar

    2013-05-01

    Throughout the history of human civilizations, cancer has been a major health problem. Its treatment has been interesting but challenging to scientists. Glutamic acid and its derivative glutamine are known to play interesting roles in cancer genesis, hence, it was realized that structurally variant glutamic acid derivatives may be designed and developed and, might be having antagonistic effects on cancer. The present article describes the state-of-art of glutamic acid and its derivatives as anticancer agents. Attempts have been made to explore the effectivity of drug-delivery systems based on glutamic acid for the delivery of anticancer drugs. Moreover, efforts have also been made to discuss the mechanism of action of glutamic acid derivatives as anticancer agents, clinical applications of glutamic acid derivatives, as well as recent developments and future perspectives of glutamic acid drug development have also been discussed.

  12. 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

  13. Metronomic Chemotherapy: Low Dose Less Toxicity Anticancer Strategy

    Directory of Open Access Journals (Sweden)

    Anjan Khadka

    2016-06-01

    Full Text Available Metronomic chemotherapy is the frequent administration of chemotherapy drugs at doses below the maximum tolerated dose and with no prolonged drug‑free break. It thus achieves a sustained low blood level of the drug without significant toxic side‑effects. Metronomic therapy leads to sustained plasma concentration of the drug without significant toxic side‑effects and hence there is reduced need for supportive therapy. However in case of conventional therapy toxicity is a concern. Metronomic chemotherapy exerts both direct and indirect effects on tumor cells and their microenvironment. It can inhibit tumor angiogenesis, stimulate anticancer immune response and also induces tumor dormancy. Optimizing a metronomic anticancer therapy is still a challenging task. New strategies are being developed to combine metronomic chemotherapy with conventional chemotherapy, radiotherapy and/or targeted therapy. An important disadvantage of this type of regimen is the empiricism in finding the optimal ‘low‑dose’ and in monitoring therapeutic efficacy during the course of treatment.

  14. Reporter nanoparticle that monitors its anticancer efficacy in real time.

    Science.gov (United States)

    Kulkarni, Ashish; Rao, Poornima; Natarajan, Siva; Goldman, Aaron; Sabbisetti, Venkata S; Khater, Yashika; Korimerla, Navya; Chandrasekar, Vineethkrishna; Mashelkar, Raghunath A; Sengupta, Shiladitya

    2016-04-12

    The ability to monitor the efficacy of an anticancer treatment in real time can have a critical effect on the outcome. Currently, clinical readouts of efficacy rely on indirect or anatomic measurements, which occur over prolonged time scales postchemotherapy or postimmunotherapy and may not be concordant with the actual effect. Here we describe the biology-inspired engineering of a simple 2-in-1 reporter nanoparticle that not only delivers a cytotoxic or an immunotherapy payload to the tumor but also reports back on the efficacy in real time. The reporter nanoparticles are engineered from a novel two-staged stimuli-responsive polymeric material with an optimal ratio of an enzyme-cleavable drug or immunotherapy (effector elements) and a drug function-activatable reporter element. The spatiotemporally constrained delivery of the effector and the reporter elements in a single nanoparticle produces maximum signal enhancement due to the availability of the reporter element in the same cell as the drug, thereby effectively capturing the temporal apoptosis process. Using chemotherapy-sensitive and chemotherapy-resistant tumors in vivo, we show that the reporter nanoparticles can provide a real-time noninvasive readout of tumor response to chemotherapy. The reporter nanoparticle can also monitor the efficacy of immune checkpoint inhibition in melanoma. The self-reporting capability, for the first time to our knowledge, captures an anticancer nanoparticle in action in vivo.

  15. Mini profile of potential anticancer properties of propofol.

    Directory of Open Access Journals (Sweden)

    Jing Song

    Full Text Available BACKGROUND: Propofol (2, 6-diisopropylphenol is an intravenous sedative-hypnotic agent administered to induce and maintain anesthesia. It has been recently revealed that propofol has anticancer properties including direct and indirect suppression of the viability and proliferation of cancer cells by promoting apoptosis in some cancer cell lines. METHODOLOGY/PRINCIPAL FINDINGS: This study aimed to establish a profile to quantitatively and functionally evaluate the anticancer properties of propofol in three cancer cell lines: non-small cell lung carcinoma cell line A549, human colon carcinoma cell line LoVo, and human breast cancer cell line SK-BR-3. We demonstrated that the expression level of caspase-3, an apoptosis biomarker, significantly increased in a dose-dependent manner after 24-h stimulation with 100 µM propofol in A549 cells, and slightly increased in LoVo cells. However, there was no change in caspase-3 expression in SK-BR-3 cells. High caspase-3 expression in A549 cells may be modulated by the ERK1/2 pathway because phosphorylated ERK1/2 dramatically reduced after propofol treatment. BAX, a major protein that promotes apoptosis in the regulation phase, was highly expressed in A549 cells after treatment with 25 µM propofol. Apoptosis induced by propofol may be associated with cancer cells carrying Kras mutations. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the anti-cancer effects of propofol, which are consistent with those of previous studies, are likely associated with the Kras mutation status. Only Kras mutation in Codon 12 instead of other Kras status has been demonstrated to play an important role in sensitizing the propofol-induced apoptosis in cancer cell lines from our study. These findings may enable us a detailed investigation of propofol/Kras-mediated cancer cell apoptosis in the future.

  16. 精子形成期基因转录表达的研究进展%Advance on research of gene expression during spermiogenesis at transcription level

    Institute of Scientific and Technical Information of China (English)

    张俊芳; 朱化彬; 张留光; 郝海生; 赵学明; 秦彤; 路永强; 王栋

    2013-01-01

    After meiosis, round spermatid develops into mature sperm through metamorphosis. During this stage, most cytoplasm in the germ cell is gradually lost. The histones associated with chromatin are replaced by transition proteins and eventually transformed into protamines. Thus, the spermatid chromatin is stringently packaged and highly concentrated. It was thought that the transcription activity of spermatid is lost and RNAs are absent in spermatid. Nevertheless, many types of transcripts are detected in recent years, including the transcripts needed during chromatin repackaged and some small RNAs, etc. Because histones in the nuclear are not replaced entirely, and there are some active sites on the chromatin, we conjectured that spermatid has some transcription activity, and this activity is regulated by hormone and epigenetic modification. These RNAs may be the residues in the spermatogenesis, or timely expressed during spermiogenesis. A deep study on gene transcription in spermiogenesis will help understand the genetic characteristics and provide the theoretic basis for reproductive control using male gamete. This article reviewed recent advances in spermiogenesis at gene transcription level and proposed the future research directions.%减数分裂后,圆形精子细胞经过一系列变态过程最终发育为成熟精子.期间,精子细胞质逐渐丢失,其 染色质组蛋白逐渐经过渡蛋白替换为鱼精蛋白,染色质被致密包装并高度浓缩.很多学者认为,精子转录活性 被关闭,不存在RNA.但近些年却在精子中检测到了种类繁多的转录本,包括精子染色质重新包装所需蛋白的 转录本及一些小分子RNA 等.由于精子核内组蛋白没有完全被鱼精蛋白替换,且染色质上包含一些核酸活性 敏感位点,推测精子存在一定的转录活性,并通过激素和表观遗传修饰等调控转录.精子中的这些RNA 一部分 是精子形成过程中残留下来的,另一部分是精子细

  17. Teratogens as anti-cancer drugs.

    Science.gov (United States)

    Blagosklonny, Mikhail V

    2005-11-01

    Most anticancer drugs are teratogens, merely because they target vital cellular functions. Conversely, some plants produce agents that intentionally target embryonic signaling pathways, precisely to cause birth defects if pregnant animals eat such plants. Cyclopamine, a teratogen produced by a flowering plant, inhibits the Hh/Gli pathway, causing developmental defects such as cyclopia (one eye in the middle of the face). In theory, selective teratogens may suppress cancer cells that reactivate embryonic pathways, while sparing most normal cells. I discuss the potential (and limits) of teratogens in cancer therapy, linking diverse topics from morning sickness of pregnancy, embryonic pathways and poisonous plants to the mechanism of action of anticancer teratogens and their combinations with less selective cytotoxic agents.

  18. New cancer treatment strategy using combination of green tea catechins and anticancer drugs.

    Science.gov (United States)

    Suganuma, Masami; Saha, Achinto; Fujiki, Hirota

    2011-02-01

    Green tea is now recognized as the most effective cancer preventive beverage. In one study, 10 Japanese-size cups of green tea daily supplemented with tablets of green tea extract limited the recurrence of colorectal polyps in humans to 50%. Thus, cancer patients who consume green tea and take anticancer drugs will have double prevention. We studied the effects of combining (-)-epigallocatechin gallate (EGCG) and anticancer drugs, focusing on inhibition of cell growth and induction of apoptosis. Numerous anticancer drugs, such as tamoxifen, COX-2 inhibitors, and retinoids were used for the experiments, and the combination of EGCG and COX-2 inhibitors consistently induced the enhancement of apoptosis. To study the mechanism of the enhancement, we paid special attention to the enhanced expressions of DDIT3 (growth arrest and DNA damage-inducible 153, GADD153), GADD45A, and CDKN1A (p21/WAF1/CIP1) genes, based on our previous evidence that a combination of EGCG and sulindac specifically induced upregulated expression of GADD153 and p21 genes in PC-9 lung cancer cells. The synergistic enhancements of apoptosis and GADD153 gene expression in human non-small cell lung cancer cells by the combination of EGCG and celecoxib were mediated through the activation of the MAPK signaling pathway. This article reviews the synergistic enhancement of apoptosis, gene expression, and anticancer effects using various combinations of EGCG and anticancer drugs, including the combination of (-)-epicatechin (EC) and curcumin. Based on the evidence, we present a new concept: green tea catechins as synergists with anticancer drugs.

  19. 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.

  20. Anticancer Properties of Phyllanthus emblica (Indian Gooseberry)

    OpenAIRE

    Tiejun Zhao; Qiang Sun; Maud Marques; Michael Witcher

    2015-01-01

    There is a wealth of information emanating from both in vitro and in vivo studies indicating fruit extract of the Phyllanthus emblica tree, commonly referred to as Indian Gooseberries, has potent anticancer properties. The bioactivity in this extract is thought to be principally mediated by polyphenols, especially tannins and flavonoids. It remains unclear how polyphenols from Phyllanthus emblica can incorporate both cancer-preventative and antitumor properties. The antioxidant function of Ph...

  1. Recent Development of Anticancer Therapeutics Targeting Akt

    OpenAIRE

    Morrow, John K.; Du-Cuny, Lei; Chen, Lu; Meuillet, Emmanuelle J.; Eugene A Mash; Powis, Garth; Zhang, Shuxing

    2011-01-01

    The serine/threonine kinase Akt has proven to be a significant signaling target, involved in various biological functions. Because of its cardinal role in numerous cellular responses, Akt has been implicated in many human diseases, particularly cancer. It has been established that Akt is a viable and feasible target for anticancer therapeutics. Analysis of all Akt kinases reveals conserved homology for an N-terminal regulatory domain, which contains a pleckstrin-homology (PH) domain for cellu...

  2. 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

  3. Advances in cobalt complexes as anticancer agents.

    Science.gov (United States)

    Munteanu, Catherine R; Suntharalingam, Kogularamanan

    2015-08-21

    The evolution of resistance to traditional platinum-based anticancer drugs has compelled researchers to investigate the cytostatic properties of alternative transition metal-based compounds. The anticancer potential of cobalt complexes has been extensively studied over the last three decades, and much time has been devoted to understanding their mechanisms of action. This perspective catalogues the development of antiproliferative cobalt complexes, and provides an in depth analysis of their mode of action. Early studies on simple cobalt coordination complexes, Schiff base complexes, and cobalt-carbonyl clusters will be documented. The physiologically relevant redox properties of cobalt will be highlighted and the role this plays in the preparation of hypoxia selective prodrugs and imaging agents will be discussed. The use of cobalt-containing cobalamin as a cancer specific delivery agent for cytotoxins will also be described. The work summarised in this perspective shows that the biochemical and biophysical properties of cobalt-containing compounds can be fine-tuned to produce new generations of anticancer agents with clinically relevant efficacies.

  4. Anticancer Drugs from Marine Flora: An Overview

    Directory of Open Access Journals (Sweden)

    N. Sithranga Boopathy

    2010-01-01

    Full Text Available Marine floras, such as bacteria, actinobacteria, cyanobacteria, fungi, microalgae, seaweeds, mangroves, and other halophytes are extremely important oceanic resources, constituting over 90% of the oceanic biomass. They are taxonomically diverse, largely productive, biologically active, and chemically unique offering a great scope for discovery of new anticancer drugs. The marine floras are rich in medicinally potent chemicals predominantly belonging to polyphenols and sulphated polysaccharides. The chemicals have displayed an array of pharmacological properties especially antioxidant, immunostimulatory, and antitumour activities. The phytochemicals possibly activate macrophages, induce apoptosis, and prevent oxidative damage of DNA, thereby controlling carcinogenesis. In spite of vast resources enriched with chemicals, the marine floras are largely unexplored for anticancer lead compounds. Hence, this paper reviews the works so far conducted on this aspect with a view to provide a baseline information for promoting the marine flora-based anticancer research in the present context of increasing cancer incidence, deprived of the cheaper, safer, and potent medicines to challenge the dreadful human disease.

  5. Tuning the anticancer activity of a novel pro-apoptotic peptide using gold nanoparticle platforms

    Science.gov (United States)

    Akrami, Mohammad; Balalaie, Saeed; Hosseinkhani, Saman; Alipour, Mohsen; Salehi, Fahimeh; Bahador, Abbas; Haririan, Ismaeil

    2016-01-01

    Pro-apoptotic peptides induce intrinsic apoptosis pathway in cancer cells. However, poor cellular penetration of the peptides is often associated with limited therapeutic efficacy. In this report, a series of peptide-gold nanoparticle platforms were developed to evaluate the anticancer activity of a novel alpha-lipoic acid-peptide conjugate, LA-WKRAKLAK, with respect to size and shape of nanoparticles. Gold nanoparticles (AuNPs) were found to enhance cell internalization as well as anticancer activity of the peptide conjugates. The smaller nanospheres showed a higher cytotoxicity, morphological change and cellular uptake compared to larger nanospheres and nanorods, whereas nanorods showed more hemolytic activity compared to nanospheres. The findings suggested that the anticancer and biological effects of the peptides induced by intrinsic apoptotic pathway were tuned by peptide-functionalized gold nanoparticles (P-AuNPs) as a function of their size and shape. PMID:27491007

  6. Suppositional area for the search of bacterial products for anticancer therapy.

    Science.gov (United States)

    Abashina, Tatiana; Laurinavichius, Kestutis; Vainshtein, Mikhail

    2016-07-01

    It is well-known that bacteria can produce compounds which show anticancer effects. In present time, it is impossible to check all bacterial species on their possible production of anticancer compounds (AC) under different conditions. Thus, it is necessary to limit the area for search of bacterial products for the anticancer therapy. We propose that production of AC by bacteria is a part of microbial biological strategy under natural conditions. We propose that bacteria in soils, in water and on plants do not meet human tumors and their AC serve for the competition with eukaryotic organisms. Most probably, an epiphytic growth of bacilli is accompanied with production of compounds inhibiting eukaryotes. According to awaited profit for the AC-producing bacteria, the epiphytic groups of bacilli show inhibition of mycelial fungi which are a natural model of eukaryotic cells. An example of strain isolation and a primary test is presented.

  7. Tuning the anticancer activity of a novel pro-apoptotic peptide using gold nanoparticle platforms

    Science.gov (United States)

    Akrami, Mohammad; Balalaie, Saeed; Hosseinkhani, Saman; Alipour, Mohsen; Salehi, Fahimeh; Bahador, Abbas; Haririan, Ismaeil

    2016-08-01

    Pro-apoptotic peptides induce intrinsic apoptosis pathway in cancer cells. However, poor cellular penetration of the peptides is often associated with limited therapeutic efficacy. In this report, a series of peptide-gold nanoparticle platforms were developed to evaluate the anticancer activity of a novel alpha-lipoic acid-peptide conjugate, LA-WKRAKLAK, with respect to size and shape of nanoparticles. Gold nanoparticles (AuNPs) were found to enhance cell internalization as well as anticancer activity of the peptide conjugates. The smaller nanospheres showed a higher cytotoxicity, morphological change and cellular uptake compared to larger nanospheres and nanorods, whereas nanorods showed more hemolytic activity compared to nanospheres. The findings suggested that the anticancer and biological effects of the peptides induced by intrinsic apoptotic pathway were tuned by peptide-functionalized gold nanoparticles (P-AuNPs) as a function of their size and shape.

  8. Diverging Novobiocin Anti-Cancer Activity from Neuroprotective Activity through Modification of the Amide Tail.

    Science.gov (United States)

    Ghosh, Suman; Liu, Yang; Garg, Gaurav; Anyika, Mercy; McPherson, Nolan T; Ma, Jiacheng; Dobrowsky, Rick T; Blagg, Brian S J

    2016-08-11

    Novobiocin is a natural product that binds the Hsp90 C-terminus and manifests Hsp90 inhibitory activity. Structural investigations on novobiocin led to the development of both anti-cancer and neuroprotective agents. The varied pharmacological activity manifested by these novobiocin analogs prompted the investigation of structure-function studies to identify these contradictory effects, which revealed that modifications to the amide side chain produce either anti-cancer or neuroprotective activity. Compounds that exhibit neuroprotective activity contain a short alkyl or cycloalkyl amide side chain. In contrast, anti-cancer agents contain five or more carbons, disrupt interactions between Hsp90α and Aha1, and induce the degradation of Hsp90-dependent client proteins.

  9. The anticancer properties of Salvia miltiorrhiza Bunge (Danshen): a systematic review.

    Science.gov (United States)

    Chen, Xiuping; Guo, Jiajie; Bao, Jiaolin; Lu, Jinjian; Wang, Yitao

    2014-07-01

    Salvia miltiorrhiza Bunge (Danshen in Chinese) is a classical Huoxue Huayu (a traditional Chinese medical term means promoting blood circulation and removing blood stasis) herb with 1000 years of clinical application. It mainly contains two groups of ingredients: the hydrophilic phenolic acids and the lipophilic tanshinones. Both groups have demonstrated multiple bioactivities, such as antioxidative stress, antiplatelet aggregation, anti-inflammation, among others. Recent data have demonstrated that its lipophilic compounds, especially the tanshinones, show potent anticancer activities both in vitro and in vivo. The anticancer effects of the hydrophilic phenolic acids have also been reported. Furthermore, tanshinones provide structural skeletons for chemical modifications, allowing for a series of derivatives of interests. This review provides a systematic summary of the anticancer profile and the underlying mechanisms of the bioactive compounds isolated from Danshen with special emphasis on tanshinones, aiming to bring new insights for further research and development of this ancient herb.

  10. Exploring Polymeric Micelles for Improved Delivery of Anticancer Agents: Recent Developments in Preclinical Studies

    Directory of Open Access Journals (Sweden)

    Wei Fan

    2013-03-01

    Full Text Available As versatile drug delivery systems, polymeric micelles have demonstrated particular strength in solubilizing hydrophobic anticancer drugs while eliminating the use of toxic organic solvents and surfactants. However, the true promise of polymeric micelles as drug carriers for cancer therapy resides in their potential ability to preferentially elevate drug exposure in the tumor and achieve enhanced anticancer efficacy, which still remains to be fully exploited. Here, we review various micellar constructs that exhibit the enhanced permeation and retention effect in the tumor, the targeting ligands that potentiate the anticancer efficacy of micellar drugs, and the polyplex micelle systems suitable for the delivery of plasmid DNA and small interference RNA. Together, these preclinical studies in animal models help us further explore polymeric micelles as emerging drug carriers for targeted cancer therapy.

  11. In vitro anticancer activity of fucoidan from Turbinaria conoides against A549 cell lines.

    Science.gov (United States)

    Marudhupandi, Thangapandi; Ajith Kumar, Thipramalai Thankappan; Lakshmanasenthil, Shanmugaasokan; Suja, Gunasekaran; Vinothkumar, Thirumalairaj

    2015-01-01

    The present study was conducted to evaluate the anticancer activity of fucoidan isolated from brown seaweed Turbinaria conoides. Extracted fucoidan contained 53 ± 0.69% of fucose and 38 ± 0.42% of sulphate, respectively. Functional groups and structural characteristics of the fucoidan were analyzed by FT-IR and NMR. In vitro anticancer effect was studied on A549 cell line. Fucoidan inhibited the growth of cancer cells in a dose-dependent manner and potent anticancer activities were 24.9-73.5% in the concentrations of 31.25-500 μg/ml. The CTC50 value against the cancer cell was found to be 45 μg/ml and the CTC50 value of normal Vero cell line is 325 μg/ml. This study suggests that the fucoidan from T. conoides could be significantly improved if the active component is further purified and tested for further investigation in various cancer cell lines.

  12. Chrysin-benzothiazole conjugates as antioxidant and anticancer agents.

    Science.gov (United States)

    Mistry, Bhupendra M; Patel, Rahul V; Keum, Young-Soo; Kim, Doo Hwan

    2015-12-01

    7-(4-Bromobutoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one, obtained from chrysin with 1,4-dibromobutane, was combined with a wide range of 6-substituted 2-aminobenzthiazoles, which had been prepared from the corresponding anilines with potassium thiocyanate. Free radical scavenging efficacies of newer analogues were measured using DPPH and ABTS assays, in addition to the assessment of their anticancer activity against cervical cancer cell lines (HeLa and CaSki) and ovarian cancer cell line (SK-OV-3) implementing the SRB assay. Cytotoxicity of titled compounds was checked using Madin-Darby canine kidney (MDCK) non-cancer cell line. Overall, 6a-r indicated remarkable antioxidant power as DPPH and ABTS(+) scavengers; particularly the presence of halogen(s) (6g, 6h, 6j-6l) was favourable with IC50 values comparable to the control ascorbic acid. Unsubstituted benzothiazole ring favored the activity of resultant compounds (6a and 6r) against HeLa cell line, whereas presence of chlorine (6g) or a di-fluoro group (6k) was a key to exert strong action against CaSki. Moreover, a mono-fluoro (6j) and a ketonic functionality (6o) were beneficial to display anticipated anticancer effects against ovarian cancer cell line SK-OV-3. The structural assignments of the new products were done on the basis of IR, (1)H NMR, (13)C NMR spectroscopy and elemental analysis.

  13. "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.

  14. Histone Methylation by Temozolomide; A Classic DNA Methylating Anticancer Drug

    Science.gov (United States)

    Pickard, Amanda J.; Diaz, Anthony Joseph; Mura, Hugo; Nyuwen, Lila; Coello, Daniel; Sheva, Saif; Maria, Nava; Gallo, James M.; Wang, Tieli

    2017-01-01

    Background/Aim The alkylating agent, temozolomide (TMZ), is considered the standard-of-care for high-grade astrocytomas –known as glioblastoma multiforme (GBM)– an aggressive type of tumor with poor prognosis. The therapeutic benefit of TMZ is attributed to formation of DNA adducts involving the methylation of purine bases in DNA. We investigated the effects of TMZ on arginine and lysine amino acids, histone H3 peptides and histone H3 proteins. Materials and Methods Chemical modification of amino acids, histone H3 peptide and protein by TMZ was performed in phosphate buffer at physiological pH. The reaction products were examined by mass spectrometry and western blot analysis. Results Our results showed that TMZ following conversion to a methylating cation, can methylate histone H3 peptide and histone H3 protein, suggesting that TMZ exerts its anticancer activity not only through its interaction with DNA, but also through alterations of protein post-translational modifications. Conclusion The possibility that TMZ can methylate histones involved with epigenetic regulation of protein indicates a potentially unique mechanism of action. The study will contribute to the understanding the anticancer activity of TMZ in order to develop novel targeted molecular strategies to advance the cancer treatment. PMID:27354585

  15. 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.

  16. Paraptosis in the anti-cancer arsenal of natural products.

    Science.gov (United States)

    Lee, Dongjoo; Kim, In Young; Saha, Sharmistha; Choi, Kyeong Sook

    2016-06-01

    Given the problems with malignant cancer cells showing innate and acquired resistance to apoptosis, we need alternative means to induce cell death in cancer. Paraptosis is a type of programmed cell death that is characterized by dilation of the endoplasmic reticulum (ER) and/or mitochondria. Although relatively little is known regarding the molecular basis of paraptosis, the underlying mechanism clearly differs from that of apoptosis. Recent studies have shown that various natural products, including curcumin, celastrol, 15d-PGJ2, ophiobolin A, and paclitaxel, demonstrate anti-cancer effects by inducing the paraptosis-associated cell death, which was commonly characterized by vacuolation derived from the ER. Perturbation of cellular proteostasis due to proteasomal inhibition and disruption of sulfhydryl homeostasis, generation of reactive oxygen species, and/or imbalanced homeostasis of ions (e.g., Ca(2+) and K(+)) appear to contribute to the accumulation of misfolded protein and proteotoxicity in this process. Given the pathophysiological importance of paraptosis and the debate regarding the importance of apoptosis in solid tumor, we need to collect the available knowledge regarding paraptosis and suggest future directions in the field. Here, we review the morphological and biochemical features of paraptosis, the natural products that induce paraptosis-associated cell death, their proposed mechanisms, and the significance of paraptosis as a potential anti-cancer strategy. Such work and future clarifications should enable the development of new strategies for preventing cancer and/or combating malignant cancer.

  17. "Ziziphus jujuba": A red fruit with promising anticancer activities.

    Science.gov (United States)

    Tahergorabi, Zoya; Abedini, Mohammad Reza; Mitra, Moodi; Fard, Mohammad Hassanpour; Beydokhti, Hossein

    2015-01-01

    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.

  18. Genetic Interactions of STAT3 and Anticancer Drug Development

    Directory of Open Access Journals (Sweden)

    Bingliang Fang

    2014-03-01

    Full Text Available 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.

  19. 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.

  20. Anti-cancer chalcones: Structural and molecular target perspectives.

    Science.gov (United States)

    Mahapatra, Debarshi Kar; Bharti, Sanjay Kumar; Asati, Vivek

    2015-06-15

    Chalcone or (E)-1,3-diphenyl-2-propene-1-one scaffold remained a fascination among researchers in the 21st century due to its simple chemistry, ease of synthesis and a wide variety of promising biological activities. Several natural and (semi) synthetic chalcones have shown anti-cancer activity due to their inhibitory potential against various targets namely ABCG2/P-gp/BCRP, 5α-reductase, aromatase, 17-β-hydroxysteroid dehydrogenase, HDAC/Situin-1, proteasome, VEGF, VEGFR-2 kinase, MMP-2/9, JAK/STAT signaling pathways, CDC25B, tubulin, cathepsin-K, topoisomerase-II, Wnt, NF-κB, B-Raf and mTOR etc. In this review, a comprehensive study on molecular targets/pathways involved in carcinogenesis, mechanism of actions (MOAs), structure activity relationships (SARs) and patents granted have been highlighted. With the knowledge of molecular targets, structural insights and SARs, this review may be helpful for (medicinal) chemists to design more potent, safe, selective and cost effective anti-cancer chalcones.

  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 induce