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Sample records for anticancer transcript-level effects

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

    International Nuclear Information System (INIS)

    Wan Hong; Liu Shuzheng

    1998-01-01

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

  2. Ultraviolet-B effects on transcript levels for photosynthetic genes are not mediated through carbohydrate metabolism

    International Nuclear Information System (INIS)

    Mackerness, S.A.H.; Surplus, S.L.; Jordan, B.R.; Thomas, B.

    1997-01-01

    The relationship between UV-B-induced changes in gene expression and carbohydrate levels in pea seedlings has been investigated. The effect of supplementary UV-B radiation on the transcript abundance for two photosynthetic genes, photosynthesis, respiration and the levels of carbohydrates was determined in fully expanded leaves of 17-d-old pea seedlings under high (HL: 350 μmol m −2 s −1 ) and low (LL: 150 μmol m −2 s 1 ) light. Supplementary UV-B caused down regulation of the photosynthetic genes in green leaves under LL and to a lesser extent under HL. In contrast to previous studies, UV-B radiation resulted in a decrease in glucose levels rather than an increase under LL. Sucrose and starch levels were not affected until longer exposure. Effects of UV-B on carbohydrate levels were, however, minimal under HL. The effects on transcript levels were most marked under LL and therefore could not be attributed to elevated carbohydrate levels. Comparison of UV-B effects on carbohydrates in source (leaf) and sink (green buds) organs indicated that changes in carbohydrates in response to UV-B are probably indirect and arise from effects of UV-B on photosynthesis in source organs. (author)

  3. 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.

  4. Ganoderma: insights into anticancer effects.

    Science.gov (United States)

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

    2016-09-01

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

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

    Science.gov (United States)

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

    2016-10-01

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

  6. Anticancer Effects of Colchicine on Hypopharyngeal Cancer.

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    Cho, Jung Hae; Joo, Young Hoon; Shin, Eun Young; Park, Eun Ji; Kim, Min Sik

    2017-11-01

    Colchicine is an alkaloid widely used for the treatment of inflammatory diseases, such as gout. It suppresses cell division by inhibiting mitosis. We investigated the anticancer effects of colchicine on human hypopharyngeal cancer cells and the mechanisms underlying its anticancer effects. XTT cell proliferation assay showed that colchicine inhibited the growth and proliferation of human hypopharyngeal cancer cells (FaDu and SNU1041) in a dose- and time-dependent manner. Colchicine also inhibited the migration, invasion, and adhesion of hypopharyngeal cancer cells in a dose-dependent manner. The levels of mRNA expression and activity of matrix metalloproteinase-9 (MMP9) and urokinase-type plasminogen activator (uPA) decreased after treatment with colchicine. Further investigation revealed that colchicine inhibited the phosphorylation of the FAK/SRC complex and paxillin. Tumor volume ratios in colchicine-treated mice (0.1 mg/kg, every 2 days for 14 days) increased less than in control mice. To our knowledge, this is the first report showing that colchicine can suppress cell invasion, migration, and adhesion through reduced expression of MMP9, the uPA system, and the FAK/SRC complex. Colchicine has the potential to prevent disease progression in hypopharyngeal cancer and may have application as an adjunctive treatment. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  7. The anticancer effect of Ocimum tenuiflorum leaves

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    Lam, S.N.

    2017-11-01

    Full Text Available Breast cancer is the leading cause of cancer deaths among females in Malaysia. Ocimum tenuiflorum L., (O. tenuiflorum commonly known as ruku in Malaysia, is usually cultivated as a garden ornamental plant because of its small purplish and some yellowish flower. The specific objective of this research is to investigate the anticancer of O. tenuiflorum against human breast cancer cell lines (MCF-7 and MDA-MB-231 and human fibroblast cell line (HS-27. In addition, another objective is to determine the mineral and heavy metal determination of O. tenuiflorum. O. tenuiflorum exhibited anticancer activity against MCF-7 (a hormone-dependent breast cancer cell line. The viability of MCF-7 cells decreased significantly after treatment with various concentrations of methanolic plant extracts (25 and 100 μg/mL, as shown via 3-(4,5-dimethylthiazol-2-yl2,5-diphenyltetrazolium bromide (MTT assay. The crude extracts show the lower IC50 (less than 100 μg/mL value against the cancer cell lines and show no effect on HS-27. The high content of calcium in the leaves of O. tenuiflorum may play a role in decreasing the risk of certain cancer. The concentrations of heavy metals (Pb and As detected in O. tenuiflorum are safe for consumption.

  8. 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. © The Author(s) 2015.

  9. 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.

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    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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Anticancer effects of Ganoderma lucidum: a review of scientific evidence.

    Science.gov (United States)

    Yuen, John W M; Gohel, Mayur Danny I

    2005-01-01

    "Lingzhi" (Ganoderma lucidum), a popular medicinal mushroom, has been used in China for longevity and health promotion since ancient times. Investigations into the anticancer activity of lingzhi have been performed in both in vitro and in vivo studies, supporting its application for cancer treatment and prevention. The proposed anticancer activity of lingzhi has prompted its usage by cancer patients. It remains debatable as to whether lingzhi is a food supplement for health maintenance or actually a therapeutic "drug" for medical proposes. Thus far there has been no report of human trials using lingzhi as a direct anticancer agent, despite some evidence showing the usage of lingzhi as a potential supplement to cancer patients. Cellular immune responses and mitogenic reactivity of cancer patients have been enhanced by lingzhi, as reported in two randomized and one nonrandomized trials, and the quality of life of 65% of lung cancer patients improved in one study. The direct cytotoxic and anti-angiogenesis mechanisms of lingzhi have been established by in vitro studies; however, clinical studies should not be neglected to define the applicable dosage in vivo. At present, lingzhi is a health food supplement to support cancer patients, yet the evidence supporting the potential of direct in vivo anticancer effects should not be underestimated. Lingzhi or its products can be classified as an anticancer agent when current and more direct scientific evidence becomes available.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-07-15

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

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

    International Nuclear Information System (INIS)

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

    2009-07-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-04-15

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

  14. 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 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.

  16. Anticancer Effects of Chenopodium ambrosiodes L. Essential Oil on ...

    African Journals Online (AJOL)

    http://dx.doi.org/10.4314/tjpr.v14i10.11. Original Research Article. Anticancer Effects of Chenopodium ambrosiodes L. Essential Oil on Human Breast Cancer MCF-7 Cells In vitro. Wang Ya-Nan*, Wu Jia-Liang, Ma Dan-Wei, Li Jiao and Zhang Du-Yu. College of Life Science, Sichuan Normal University, Chengdu 610101, ...

  17. Curcumin mediates anticancer effects by modulating multiple cell signaling pathways.

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    Kunnumakkara, Ajaikumar B; Bordoloi, Devivasha; Harsha, Choudhary; Banik, Kishore; Gupta, Subash C; Aggarwal, Bharat B

    2017-08-01

    Curcumin, a component of a spice native to India, was first isolated in 1815 by Vogel and Pelletier from the rhizomes of Curcuma longa (turmeric) and, subsequently, the chemical structure of curcumin as diferuloylmethane was reported by Milobedzka et al. [(1910) 43., 2163-2170]. Since then, this polyphenol has been shown to exhibit antioxidant, anti-inflammatory, anticancer, antiviral, antibacterial, and antifungal activities. The current review primarily focuses on the anticancer potential of curcumin through the modulation of multiple cell signaling pathways. Curcumin modulates diverse transcription factors, inflammatory cytokines, enzymes, kinases, growth factors, receptors, and various other proteins with an affinity ranging from the pM to the mM range. Furthermore, curcumin effectively regulates tumor cell growth via modulation of numerous cell signaling pathways and potentiates the effect of chemotherapeutic agents and radiation against cancer. Curcumin can interact with most of the targets that are modulated by FDA-approved drugs for cancer therapy. The focus of this review is to discuss the molecular basis for the anticancer activities of curcumin based on preclinical and clinical findings. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  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. © 2016 Elsevier Inc. All rights reserved.

  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. Anti-cancer effects of xanthones from pericarps of mangosteen.

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    Akao, Yukihiro; Nakagawa, Yoshihito; Iinuma, Munekazu; Nozawa, Yoshinori

    2008-03-01

    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; alpha-mangostin, beta-mangostin, gamma-mangostin, and methoxy-beta-mangostin in various human cancer cells. These xanthones are different in the number of hydroxyl and methoxy groups. Except for methoxy-beta-mangostin, the other three xanthones strongly inhibited cell growth at low concentrations from 5 to 20 microM in human colon cancer DLD-1 cells. Our recent study focused on the mechanism of alpha-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 alpha-mangostin and beta-Mangostin, and S arrest by gamma-mangostin. alpha-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 alpha-mangostin and anti-cancer drug 5-FU was to be noted. alpha-Mangostin was found to have a cancer preventive effect in rat carcinogenesis bioassay and the extract from pericarps, which contains mainly alpha-mangostin and gamma-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 anti-cancer drugs.

  1. Black cumin seeds show promising anti-cancer effects

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    Editorial Office

    2017-02-01

    Full Text Available Lung cancer is responsible for millions of death worldwide each year and it is the second most common cancer in both men and women. According to the American Cancer Society, lung cancer is responsible for about 1 in 4 cancer deaths and 14% of all new cases. More and more people require treatment, but due to the side effects and complications of modern drugs, there has been a growing interest in naturally occurring compounds with anti-cancer potential. Black cumin seed is one of the most promising and extensively studied plants which could provide support in considering this compound as an emerging drug.

  2. 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.

  3. Absorption, metabolism, anti-cancer effect and molecular targets of epigallocatechin gallate (EGCG): An updated review.

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    Gan, Ren-You; Li, Hua-Bin; Sui, Zhong-Quan; Corke, Harold

    2018-04-13

    Green tea is one of the most popular beverages in the world, especially in Asian countries. Consumption of green tea has been demonstrated to possess many health benefits, which mainly attributed to the main bioactive compound epigallocatechin gallate (EGCG), a flavone-3-ol polyphenol, in green tea. EGCG is mainly absorbed in the intestine, and gut microbiota play a critical role in its metabolism prior to absorption. EGCG exhibits versatile bioactivities, with its anti-cancer effect most attracting due to the cancer preventive effect of green tea consumption, and a great number of studies intensively investigated its anti-cancer effect. In this review, we therefore, first stated the absorption and metabolism process of EGCG, and then summarized its anti-cancer effect in vitro and in vivo, including its manifold anti-cancer actions and mechanisms, especially its anti-cancer stem cell effect, and next highlighted its various molecular targets involved in cancer inhibition. Finally, the anti-cancer effect of EGCG analogs and nanoparticles, as well as the potential cancer promoting effect of EGCG were also discussed. Understanding of the absorption, metabolism, anti-cancer effect and molecular targets of EGCG can be of importance to better utilize it as a chemopreventive and chemotherapeutic agent.

  4. Synergistic Effect of Eicosapentaenoic Acid on Antiproliferative Action of Anticancer Drugs in a Cancer Cell Line Model.

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    Ogo, Ayako; Miyake, Sachi; Kubota, Hisako; Higashida, Masaharu; Matsumoto, Hideo; Teramoto, Fusako; Hirai, Toshihiro

    2017-01-01

    It has been found experimentally and clinically that eicosapentaenoic acid (EPA) exerts an anticancer effect and that it has a minimal adverse event profile relative to other anticancer drugs. Any synergy between EPA and other anticancer drugs could be of therapeutic relevance, especially in elderly or high-risk patients. Therefore, we investigated the synergism between anticancer drugs and EPA experimentally. EPA was coadministered in vitro with various anticancer drugs (paclitaxel, docetaxel, 5-fluorouracil and cis-diamminedichloridoplatinum[II]) to TE-1 cells, which were derived from human esophageal cancer tumors. Cell proliferation was measured by the water soluble tetrazolium-1 method. Sub-threshold concentrations of EPA, which alone produced no anticancer effect, caused a synergistic suppressive effect on TE-1 cell proliferation when combined with other anticancer agents. Coadministration of EPA with other anticancer drugs may represent a new therapeutic paradigm offering a reduced side effect profile. © 2017 S. Karger AG, Basel.

  5. Therapeutic Effectiveness of Anticancer Phytochemicals on Cancer Stem Cells.

    Science.gov (United States)

    Oh, Jisun; Hlatky, Lynn; Jeong, Yong-Seob; Kim, Dohoon

    2016-06-30

    Understanding how to target cancer stem cells (CSCs) may provide helpful insights for the development of therapeutic or preventive strategies against cancers. Dietary phytochemicals with anticancer properties are promising candidates and have selective impact on CSCs. This review summarizes the influence of phytochemicals on heterogeneous cancer cell populations as well as on specific targeting of CSCs.

  6. 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.

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

    Science.gov (United States)

    Nakamura, Kazuki; Shinozuka, Kazumasa; Yoshikawa, Noriko

    2015-01-01

    Cordyceps sinensis, a fungus that parasitizes on the larva of Lepidoptera, has been used as a valued traditional Chinese medicine. We investigated the effects of water extracts of Cordyceps sinensis (WECS), and particularly focused on its anticancer and antimetastatic actions. Based on in vitro studies, we report that WECS showed an anticancer action, and this action was antagonized by an adenosine A3 receptor antagonist. Moreover, this anticancer action of WECS was promoted by an adenosine deaminase inhibitor. These results suggest that one of the components of WECS with an anticancer action might be an adenosine or its derivatives. Therefore, we focused on cordycepin (3'-deoxyadenosine) as one of the active ingredients of WECS. According to our experiments, cordycepin showed an anticancer effect through the stimulation of adenosine A3 receptor, followed by glycogen synthase kinase (GSK)-3β activation and cyclin D1 suppression. Cordycepin also showed an antimetastatic action through inhibiting platelet aggregation induced by cancer cells and suppressing the invasiveness of cancer cells via inhibiting the activity of matrix metalloproteinase (MMP)-2 and MMP-9, and accelerating the secretion of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 from cancer cells. In conclusion, cordycepin, an active component of WECS, might be a candidate anticancer and antimetastatic agent. Copyright © 2014 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Kazuki Nakamura

    2015-01-01

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

  9. The potential of brown-algae polysaccharides for the development of anticancer agents: An update on anticancer effects reported for fucoidan and laminaran.

    Science.gov (United States)

    Sanjeewa, K K Asanka; Lee, Jung-Suck; Kim, Won-Suck; Jeon, You-Jin

    2017-12-01

    In recent decades, attention to cancer-preventive treatments and studies on the development of anticancer drugs have sharply increased owing to the increase in cancer-related death rates in every region of the world. However, due to the adverse effects of synthetic drugs, much attention has been given to the development of anticancer drugs from natural sources because of fewer side effects of natural compounds than those of synthetic drugs. Recent studies on compounds and crude extracts from marine algae have shown promising anticancer properties. Among those compounds, polysaccharides extracted from brown seaweeds play a principal role as anticancer agents. Especially, a number of studies have revealed that polysaccharides isolated from brown seaweeds, such as fucoidan and laminaran, have promising effects against different cancer cell types in vitro and in vivo. Herein, we reviewed in vitro and in vivo anticancer properties reported for fucoidan and laminaran toward various cancer cells from 2013 to 2016. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. [Molecular mechanism regulating effect of anti-cancer agents].

    Science.gov (United States)

    Saya, Hideyuki

    2009-01-01

    Faithful genome duplication is achieved by accurate coordination between DNA replication and chromosome segregation. Abnormalities occurring in this process are checked by biochemical signal transduction pathways, called checkpoints, which ensure the orderly progression of events in the cell cycle. Checkpoints prevent transition into subsequent phases until all processes in the previous phase are completed. Defects in cell cycle checkpoints result in gene mutations, chromosome damage, and aneuploidy, all of which contribute to tumorigenesis. However, it has recently been uncovered that the impairment of checkpoint function is the major reason why DNA damaging anti-cancer agents can selectively kill cancer cells. Given that G1 and G2 checkpoint functions are generally impaired in cancer cells, cells with DNA damage are unable to maintain G2 arrest and eventually die as they enter mitosis. This process is known as mitotic catastrophe.

  11. 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.

  12. Zinc finger protein 521 overexpression increased transcript levels of ...

    Indian Academy of Sciences (India)

    2016-02-12

    Feb 12, 2016 ... 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 ...

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

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    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.

  14. 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.

  15. Anticancer effects of clinically acceptable colchicine concentrations on human gastric cancer cell lines.

    Science.gov (United States)

    Lin, Zu-Yau; Kuo, Chao-Hung; Wu, Deng-Chyang; Chuang, Wan-Long

    2016-02-01

    Colchicine is a very cheap microtubule destabilizer. Because microtubules are an ideal target for anticancer drugs, the purpose of this study was to investigate whether clinically acceptable colchicine concentrations have anticancer effects on gastric cancer cells, and its possible anticancer mechanisms. Two human gastric cancer cell lines (i.e., AGS and NCI-N87) were investigated by proliferative assay, microarray, quantitative reverse transcriptase-polymerase chain reaction, and a nude mice study using clinically acceptable colchicine concentrations (2 ng/mL and 6 ng/mL for in vitro tests and 0.07 mg colchicine/kg/d for in vivo tests). Our results showed that colchicine had the same inhibitory effects on the proliferation of both cell lines. The antiproliferative effects of colchicine on both cell lines were achieved only at the concentration of 6 ng/mL (p colchicine, compared with 2 ng/mL colchicine. Among these genes, only the upregulated DUSP1 gene may contribute to the antiproliferative effects of colchicine on gastric cancer cells. The nude mice (BALB/c-nu) experiment showed that colchicine-treated mice after 14 days of treatment had lower increased tumor volume ratios (p = 0.0199) and tumor growth rates (p = 0.024) than the control mice. In conclusion, colchicine has potential for the palliative treatment of gastric cancer. However, the anticancer effects are achieved only at high clinically acceptable colchicine concentrations. Monitoring the colchicine plasma concentration is mandatory if this drug is applied for the palliative treatment of gastric cancer. Copyright © 2016. Published by Elsevier Taiwan.

  16. Cytotoxic, anti-cancer, and anti-microbial effects of different extracts obtained from Artemisia rupestris.

    Science.gov (United States)

    Nokerbek, Shamshabanu; Sakipova, Zuriyadda; Chalupová, Marta; Nejezchlebová, Marcela; Hošek, Jan

    2017-01-01

    Artemisia rupestris is a part of traditional Kazakh folk medicine. Extracts obtained from this plant are used to treat various diseases, including cancer. This study evaluates the anti-microbial, cytotoxic, and anti-cancer effects of different extracts of the plant. Different extraction techniques were used and the resultant activities were compared. Extracts of A. rupestris were prepared from the flowers plus the leaves and from the stems. The antimicrobial activity against Candida albicans and Staphylococcus aureus was quantified. Cell lines L1210 and THP-1 were used to evaluate the cytotoxic potential of these extracts in vitro. The anti-cancer effect was tested using L1210-induced tumorgenesis in mouse model. The aqueous extract of stems was the most active against C. albicans, whereas the methanolic extract of flowers plus leaves especially inhibited the growth of S. aureus. The aqueous extracts were found to be non-cytotoxic for both cell lines, whereas the lipophilic extracts showed cytotoxic effects. The extract obtained from flowers plus leaves was more cytotoxic than that from stems. The tested extracts showed no anti-cancer potential. The results obtained testify to the relatively safe consumption of aqueous extracts of A. rupestris, but lipophilic extracts showed toxic effects and their consumption should be considered more carefully.Key words: L1210 cell line THP-1 cell line microwave-assisted extraction ultrasonic-assisted extraction Candida albicans Staphylococcus aureus.

  17. Preparation of slow release anticancer drug by means of radiation technique and IT's therapeutic effect on sold tumor of mice

    International Nuclear Information System (INIS)

    Li Ximing; Shen Weiming; Liu Chengjie; Hu Xu

    1991-01-01

    In order to minimize the toxic effect of chemotherapy of malignant tumors, the authors use a method of radiation induced cast polymerization of hydrophilic monomer at low temperature for immobilization the anticancer drug, 5-Fluorouracil, into the polymer matrix. The anticancer drug-polymer composite called slow release anticancer drug was used for treatment the transplantable squamous cell carcinoma in mice 615 and the transplantable sarcoma (S180) in Kunming mice. There were marked difference between the treated group and the control group. That is the higher inhibition ratio and lower toxic effect were reported

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

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    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.

  19. Effect of methionine and glucosamine conjugation on the anticancer ...

    Indian Academy of Sciences (India)

    ... 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.

  20. Molecular Mechanisms of Anticancer Effects of Phytoestrogens in Breast Cancer.

    Science.gov (United States)

    Hsieh, Chia-Jung; Hsu, Ya-Ling; Huang, Ya-Fang; Tsai, Eing-Mei

    2018-01-01

    Phytoestrogens derived from plants exert estrogenic as well as antiestrogenic effects and multiple actions within breast cancer cells. Chemopreventive properties of phytoestrogens have emerged from epidemiological observations. In recent clinical research studies, phytoestrogens are safe and may even protect against breast cancer. In this brief review, the molecular mechanisms of phytoestrogens on regulation of cell cycle, apoptosis, estrogen receptors, cell signaling pathways, and epigenetic modulations in relation to breast cancer are discussed. Phytoestrogens have a preferential affinity for estrogen receptor (ER)-β, which appears to be associated with antiproliferative and anticarcinogenic effects. Moreover, while phytoestrogens not only inhibit ER-positive but also ER-negative breast cancer cells, the possibility of epigenetic modulation playing an important role is also discussed. In conclusion, as there are multiple targets and actions of phytoestrogens, extensive research is still necessary. However, due to low toxicity, low cost, and easy availability, their potent chemoprevention effects deserve further study. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

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    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.

  2. 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.

  3. Chiral resolution and anticancer effect of xanthones from Garcinia paucinervis.

    Science.gov (United States)

    Jia, Cui-Cui; Xue, Jing-Jing; Gong, Chi; Li, Xin-Yu; Li, Da-Hong; Li, Zhan-Lin; Hua, Hui-Ming

    2018-02-21

    Bioassay-guided fractionation of the dichloromethane-soluble portion of the stems of Garcinia paucinervis led to the isolation of eight new xanthones, including three pairs of enantiomers, (+) and (-) paucinervins L-N (1a-3a, and 1b-3b), one optically pure compound, (-) paucinervin O (4), and one new analogue, paucinervin P (5), as well as thirteen known xanthones (6-18). Their structures were established by detailed analysis of extensive spectroscopic data. The absolute configurations of 1-4 were confirmed by ECD calculations. All the isolates 1-18 displayed antiproliferative effect against HL-60 with IC 50 values ranging from 0.87 to 29.14 μM, of which compound 5 was the most active. Compounds 6, and 14 exhibited potential inhibitory activity against PC-3 cells, while compounds 5-7, 14, and 16-17 displayed cytotoxic potency against Caco-2 cells. A preliminary structure-activity relationship was also discussed. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. 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.

  5. 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.

  6. Anti-cancer effect of Scutellaria baicalensis in combination with cisplatin in human ovarian cancer cell.

    Science.gov (United States)

    Choi, Bo Yoon; Joo, Jong Cheon; Lee, Yeon Kyu; Jang, Ik-Soon; Park, Soo Jung; Park, Yoon Jung

    2017-05-25

    Ovarian cancer is one of the major causes of death among females in worldwide. Cisplatin is a primary anti-cancer drug against ovarian cancer, but the recurrent tumors after treatment frequently show acquired chemoresistance. Extract of Scutellaria baicalensis (SbE) has been reported to have functional compounds including baicalin, which has anti-cancer effects. However, the anti-cancer effects of SbE in ovarian cancer and its underlying mechanisms are elusive. We investigated that the effects of SbE and/or cisplatin on cell death in the cisplatin sensitive ovarian cancer cell line A2780 (CSC) and the counterpart cell line that has cisplatin resistance (CRC). Molecular mechanisms of the effects, focusing on apoptosis and autophagy, were examined. Treatment of cisplatin or SbE reduced cell viability significantly in CSC and too much lesser extent in CRC. Cisplatin-induced cell death in CSC was mediated by p53-induced apoptosis acompanied by expresson of damage-regulated autophagy modulator (DRAM). In CRC, decreased DRAM expression (p cisplatin resistance. Treatment of SbE also induced cell death in CSC by p53-dependent apoptosis, not in CRC. Autophagy was not induced by neither cisplatin nor SbE. Intriguingly, the combinational treatment of SbE and cisplatin significantly decreased cell viability in CRC. The cell death was mediated by autophagy with increased expression of Atg5 and Atg12 (p cisplatin was effective in CRC, leading to cell death via Beclin1-independent autophagy, suggesting that SbE treatment in combination with cisplatin has a potential as a chemotherapeutic agent in cisplatin-resistant ovarian cancer.

  7. Curcumin induced autophagy anticancer effects on human lung adenocarcinoma cell line A549.

    Science.gov (United States)

    Liu, Furong; Gao, Song; Yang, Yuxuan; Zhao, Xiaodan; Fan, Yameng; Ma, Wenxia; Yang, Danrong; Yang, Aimin; Yu, Yan

    2017-09-01

    To investigate the anticancer effects of curcumin-induced autophagy and its effects on the human lung adenocarcinoma A549 cell line, inverted phase contrast microscopy was used to observe alterations to the cytomorphology of cells. An MTT assay was used to measure cell viability. Autophagy was detected using acridine orange (AO) staining and 3-methyladenine (3-MA) was used as an autophagy-specific inhibitor. Dose- and time-dependent A549 cell viability inhibition was observed following curcumin treatment. A dose-dependent increase in the red fluorescent structures in A549 cells was identified following curcumin treatment for 48 h through AO staining. In addition, the activation of autophagy was determined through changes in the number of autophagic vesicles (AVs; fluorescent particles) infected with monodansylcadaverine (MDC). The fluorescence intensity and density of AVs in the curcumin-treated groups were higher at 48 h compared with the control group. Finally, the MTT assay demonstrated that the survival rates of the curcumin-treated cells were increased when pretreated with 3-MA for 3 h, indicating that the inhibitory effect of curcumin on A549 cells is reduced following the inhibition of autophagy. Furthermore, AO and MDC staining confirmed that 3-MA does inhibit the induction of autophagy. Thus, it was hypothesized that the induction of autophagy is partially involved in the reduction of cell viability observed following curcumin treatment. The anticancer effects of curcumin on A549 cells can be reduced using autophagy inhibitors. This suggests a possible cancer therapeutic application of curcumin through the activation of autophagy. These findings have improved the understanding of the mechanism underlying the anticancer property of curcumin.

  8. Evaluation of anticancer effects and enhanced doxorubicin cytotoxicity of xanthine derivatives using canine hemangiosarcoma cell lines.

    Science.gov (United States)

    Motegi, Tomoki; Katayama, Masaaki; Uzuka, Yuji; Okamura, Yasuhiko

    2013-10-01

    Methylxanthine derivatives increase cAMP and are known to have diuretic, cardiac, and central nervous system stimulatory effects. Moreover, caffeine inhibits the development of tumors induced by various carcinogens. The aim of this work was to elucidate the anticancer effects on apoptosis of xanthine derivatives alone and with doxorubicin in canine hemangiosarcoma cells. Xanthine derivatives with or without doxorubicin were administered to cells, and the effects were investigated by measuring tumor cell proliferation, cell death (cytotoxicity) induction, and apoptosis by the expression of annexin V or caspase 3/7. Both caffeine and theophylline induced apoptosis, and the treated cells expressed annexin V and caspase 3/7. Both drugs enhanced doxorubicin-induced cytotoxicity; however, hypoxanthine showed no effect. These results indicate that theophylline is similar to caffeine; both drugs may enhance doxorubicin-induced cytotoxicity by inhibiting ATM/ATR kinases. Our data suggest that caffeine and theophylline have anticancer effects and can improve the treatment effect in canine hemangiosarcoma patients. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Potential effects of gamma irradiation on the stability and therapeutic activity of anticancer drug, doxorubicin

    Directory of Open Access Journals (Sweden)

    Fatmah M. Alshammari

    2017-04-01

    Full Text Available Cancer therapy has progressed dramatically in recent years. In order to decrease the dose and side effects of the anticancer drug, the therapeutic options for patients with cancer include increasingly complex combinations of chemotherapy and radiotherapy. This combination may cause overlapping interaction between the two types of treatment and affect the stability of the anticancer drug. In this study, the effect of gamma irradiation on the stability and therapeutic activity of one anticancer drug (Doxorubicin was studied. For this purpose, doxorubicin drug characterized by two methods, at first, in-vitro study, before and after drug irradiation with different doses of gamma rays (2, 5, 20, 100 GY which achieved through measuring the dielectric relaxation and absorption spectrum of drug solution. Secondly, in-vivo studies, where the unirradiated and the drug, which later exposed to gamma rays, were injected respectively into 6 groups of mice (3 mice in each group. The dielectric relaxation and absorption spectrum were studded for hemoglobin of the injected mice. The results for the in-vitro study indicate that the values of dielectric parameters show unnoticeable change for drug molecules before and after irradiation as compared with the control. The results for in-vivo study indicated an increase in the values of relaxation time and Cole- Cole parameter, that may as a result of changes in the conformational structure in hemoglobin molecules which may affect their properties and hence RBC's physiological functions. The absorption spectra of hemoglobin molecules show an increase in the amplitude of the characteristic bands with irradiation dose indicate an increase of the oxygen binding capacity with hemoglobin. It was concluded that combination between the drugs and gamma irradiation can be used as a powerful conjunction that may give us the benefit chemo and radiotherapy treatment.

  10. The effect of ultrasonificated extracts of Spirulina maxima on the anticancer activity.

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    Oh, Sung-Ho; Ahn, Juhee; Kang, Do-Hyung; Lee, Hyeon-Yong

    2011-04-01

    The effect of ultrasonic extraction on extraction yields, cytotoxicity, and anticancer activity of Spirulina maxima was investigated in this study. Optimal extraction conditions were determined as 60 kHz frequency at 60°C for 30 min with 120 W intensity, which resulted in 19.3% of extraction yields and 19.1% of cytotoxicity on normal human cells. Yields from conventional water and ethanol extraction were 15.8% at 100°C and 8.3% at 80°C, respectively. It was found that the extracts obtained by ultrasonic extraction process selectively inhibited the digestive-related cancer cell lines, such as human stomach cancer cells, having 89% of the highest inhibition ratio and 4.5 of the highest selectivity. In adding 0.5 mg/mL of the extract, human promyelocytic leukemia cells' cell differentiation was increased 1.72 times over that of the control. Expression level of B cell lymphoma-2 from Hep3B cell was also effectively suppressed by the extract obtained at 60 kHz and 60°C, leading to the inhibition of the early step of carcinogenesis. This work suggests that anticancer activity of the extracts is due to water-soluble polysaccharides rather than proteins and is further supported by the result that the ultrasonification extraction process can efficiently extract relatively intact polysaccharides rather than digesting the proteins in S. maxima by matrix assisted laser desorption ionization-time of flight and high performance size exclusion chromatography chromatogram analyses. Therefore, ultrasonic extraction increases both extraction yield and the biological activity of S. maxima extracts, which might be useful as an alternative natural anticancer agent in the medical and food industries.

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

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    Park Chan-Yol

    2000-07-01

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

  12. 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.

  13. 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.

  14. PUMA mediates the anti-cancer effect of osimertinib in colon cancer cells.

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    Guo, Lingchuan; Huang, Shan; Wang, Xinwei

    2017-01-01

    Osimertinib, an irreversible EGFR/HER2 inhibitor, has been found to be effective in the cancer cell with EGFR gene mutations in preclinical lung cancer models. However, the effect of osimertinib in colorectal cancer (CRC) cells is unclear. In the present study, we investigated how osimertinib suppresses CRC cells growth and potentiates effects of other chemotherapeutic drugs. We found that p73-mediated osimertinib-induced p53 upregulated modulator of apoptosis (PUMA) expression irrespective of p53 status following PI3K/AKT pathway inhibition in CRC cells. Furthermore, PUMA is required for osimertinib-induced apoptosis. In addition, osimertinib also synergized with 5-FU to induce significant apoptosis via PUMA in CRC cells. These results demonstrated a critical role of PUMA in mediating the anticancer effects of osimertinib and suggest that PUMA induction can be used as an indicator of osimertinib sensitivity.

  15. The Anti-Cancer Effect of Polyphenols against Breast Cancer and Cancer Stem Cells: Molecular Mechanisms

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    Ahmed Abdal Dayem

    2016-09-01

    Full Text Available The high incidence of breast cancer in developed and developing countries, and its correlation to cancer-related deaths, has prompted concerned scientists to discover novel alternatives to deal with this challenge. In this review, we will provide a brief overview of polyphenol structures and classifications, as well as on the carcinogenic process. The biology of breast cancer cells will also be discussed. The molecular mechanisms involved in the anti-cancer activities of numerous polyphenols, against a wide range of breast cancer cells, in vitro and in vivo, will be explained in detail. The interplay between autophagy and apoptosis in the anti-cancer activity of polyphenols will also be highlighted. In addition, the potential of polyphenols to target cancer stem cells (CSCs via various mechanisms will be explained. Recently, the use of natural products as chemotherapeutics and chemopreventive drugs to overcome the side effects and resistance that arise from using chemical-based agents has garnered the attention of the scientific community. Polyphenol research is considered a promising field in the treatment and prevention of breast cancer.

  16. Dihydrochalcone Compounds Isolated from Crabapple Leaves Showed Anticancer Effects on Human Cancer Cell Lines

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    Xiaoxiao Qin

    2015-11-01

    Full Text Available Seven dihydrochalcone compounds were isolated from the leaves of Malus crabapples, cv. “Radiant”, and their chemical structures were elucidated by UV, IR, ESI-MS, 1H-NMR and 13C-NMR analyses. These compounds, which include trilobatin (A1, phloretin (A2, 3-hydroxyphloretin (A3, phloretin rutinoside (A4, phlorizin (A5, 6′′-O-coumaroyl-4′-O-glucopyranosylphloretin (A6, and 3′′′-methoxy-6′′-O-feruloy-4′-O-glucopyranosyl-phloretin (A7, all belong to the phloretin class and its derivatives. Compounds A6 and A7 are two new rare dihydrochalcone compounds. The results of a MTT cancer cell growth inhibition assay demonstrated that phloretin and these derivatives showed significant positive anticancer activities against several human cancer cell lines, including the A549 human lung cancer cell line, Bel 7402 liver cancer cell line, HepG2 human ileocecal cancer cell line, and HT-29 human colon cancer cell line. A7 had significant effects on all cancer cell lines, suggesting potential applications for phloretin and its derivatives. Adding a methoxyl group to phloretin dramatically increases phloretin’s anticancer activity.

  17. 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

  18. Anticancer effect of triterpenes from Ganoderma lucidum in human prostate cancer cells.

    Science.gov (United States)

    Qu, Lijun; Li, Sumei; Zhuo, Yumin; Chen, Jianfan; Qin, Xiaoping; Guo, Guoqing

    2017-12-01

    Ganoderma lucidum , within the Polyporaceae family of Basidiomycota, is a popular traditional remedy medicine used in Asia to promote health and longevity. Compounds extracted from G. lucidum have revealed anticancer, antioxidant and liver protective effects. G. lucidum has been associated with prostate cancer cells. G. lucidum extracts contain numerous bioactive components; however, the exact functional monomer is unknown and the role of triterpenes from G. lucidum (GLT) in prostate cancer remain obscure. The present study investigated the effects of GLT on cell viability, migration, invasion and apoptosis in DU-145 human prostate cancer cells. The results demonstrated that a high dose (2 mg/ml) of GLT inhibits cell viability in a dose- and time-dependent manner by the regulation of matrix metalloproteases. Furthermore, GLT induced apoptosis of DU-145 cells. In general, GLT exerts its effect on cancer cells via numerous mechanisms and may have potential therapeutic use for the prevention and treatment of cancer.

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

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    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.

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

    International Nuclear Information System (INIS)

    Sasaki, Kazuhito; Hiyoshi, Masaya; Kaneko, Manabu; Kitayama, Joji; Takahashi, Koki; Nagawa, Hirokazu; Tsuno, Nelson H; Sunami, Eiji; Tsurita, Giichiro; Kawai, Kazushige; Okaji, Yurai; Nishikawa, Takeshi; Shuno, Yasutaka; Hongo, Kumiko

    2010-01-01

    Chloroquine (CQ), the worldwide used anti-malarial drug, has recently being focused as a potential anti-cancer agent as well as a chemosensitizer when used in combination with anti-cancer drugs. It has been shown to inhibit cell growth and/or to induce cell death in various types of cancer. 5-Fluorouracil (5-FU) is the chemotherapeutic agent of first choice in colorectal cancer, but in most cases, resistance to 5-FU develops through various mechanisms. Here, we focused on the combination of CQ as a mechanism to potentiate the inhibitory effect of 5-FU on human colon cancer cells. HT-29 cells were treated with CQ and/or 5-FU, and their proliferative ability, apoptosis and autophagy induction effects, and the affection of the cell cycle were evaluated. The proliferative ability of HT-29 was analyzed by the MTS assay. Apoptosis was quantified by flow-cytometry after double-staining of the cells with AnnexinV/PI. The cell cycle was evaluated by flow-cytometry after staining of cells with PI. Autophagy was quantified by flow-cytometry and Western blot analysis. Finally, to evaluate the fate of the cells treated with CQ and/or 5-FU, the colony formation assay was performed. 5-FU inhibited the proliferative activity of HT-29 cells, which was mostly dependent on the arrest of the cells to the G0/G1-phase but also partially on apoptosis induction, and the effect was potentiated by CQ pre-treatment. The potentiation of the inhibitory effect of 5-FU by CQ was dependent on the increase of p21 Cip1 and p27 Kip1 and the decrease of CDK2. Since CQ is reported to inhibit autophagy, the catabolic process necessary for cell survival under conditions of cell starvation or stress, which is induced by cancer cells as a protective mechanism against chemotherapeutic agents, we also analyzed the induction of autophagy in HT-29. HT-29 induced autophagy in response to 5-FU, and CQ inhibited this induction, a possible mechanism of the potentiation of the anti-cancer effect of 5-FU. Our

  1. Invertase Suc2-mediated inulin catabolism is regulated at the transcript level in Saccharomyces cerevisiae.

    Science.gov (United States)

    Yang, Fan; Liu, Zhi-Cheng; Wang, Xue; Li, Li-Li; Yang, Lan; Tang, Wen-Zhu; Yu, Zhi-Min; Li, Xianzhen

    2015-04-17

    Invertase Suc2 was recently identified as a key hydrolase for inulin catabolism in Saccharomyces cerevisiae, whereas the Suc2 activity degrading inulin varies greatly in different S. cerevisiae strains. The molecular mechanism causing such variation remained obscure. The aim of this study is to investigate how Suc2 activity is regulated in S. cerevisiae. The effect of SUC2 expression level on inulin hydrolysis was investigated by introducing different SUC2 genes or their corresponding promoters in S. cerevisiae strain BY4741 that can only weakly catabolize inulin. Both inulinase and invertase activities were increased with the rising SUC2 expression level. Variation in the promoter sequence has an obvious effect on the transcript level of the SUC2 gene. It was also found that the high expression level of SUC2 was beneficial to inulin degradation and ethanol yield. Suc2-mediated inulin catabolism is regulated at transcript level in S. cerevisiae. Our work should be valuable for engineering advanced yeast strains in application of inulin for ethanol production.

  2. Cytogenotoxic effects of two potential anticancer Ruthenium(III Schiff Bases complexes

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    Izet Eminovic

    2016-10-01

    Full Text Available Introduction: Treatment of cancer has been subject of great interest. Researchers are continuously searching for new medicines. In this sense, ruthenium complexes have big potential. Some evidences suggest that ruthenium compounds possess anticancer activities. We synthesized two recently published ruthenium(III complexes with bidentate O,N and tridentate O,O,N Schiff bases derived from 5-substituted salicylaldehyde and aminophenol or anilineare. These compounds showed affinity for binding to the DNA molecule, however, insufficient data are available regarding their possible toxic effects on biological systems.Methods: In the present study we evaluated genotoxic, cytotoxic, and cytostatic effects of Na[RuCl2(L12] and Na[Ru(L22], using the Allium cepa assay.Results: Different toxic effects were observed depending on the substance, tested concentration, and endpoint measured. In general, the tested compounds significantly lowered the root growth and mitotic index values as compared to the control group. Additionally, a wide range of abnormal mitotic stages, both clastogenic and non-clastogenic were observed in the treated cells. Na[RuCl2(L12] significantly increased the frequency of sticky metaphases, chromosome bridges, micronuclei, impaired chromosome segregation, as well as number of apoptotic and necrotic cells over the controls. In contrast, Na[Ru(L22] did not show significant evidence of genotoxicity with regard to chromosome aberrations and micronuclei, however, significant differences were detected in the number of apoptotic and necrotic cells when the highest concentration was applied.Conclusions: In this study we demonstrated antiproliferative effects of Na[RuCl2(L12] and Na[Ru(L22]. At clinical level, these results could be interesting for further studies on anticancer potential of the ruthenium(III complexes using animal models.

  3. In vitro antioxidant and anticancer effects of solvent fractions from Prunella vulgaris var. lilacina.

    Science.gov (United States)

    Hwang, Yu-Jin; Lee, Eun-Ju; Kim, Haeng-Ran; Hwang, Kyung-A

    2013-11-09

    Recently, considerable attention has been focused on exploring the potential antioxidant properties of plant extracts or isolated products of plant origin. Prunella vulgaris var. lilacina is widely distributed in Korea, Japan, China, and Europe, and it continues to be used to treat inflammation, eye pain, headache, and dizziness. However, reports on the antioxidant activities of P. vulgaris var. lilacina are limited, particularly concerning the relationship between its phenolic content and antioxidant capacity. In this study, we investigated the antioxidant and anticancer activities of an ethanol extract from P. vulgaris var. lilacina and its fractions. Dried powder of P. vulgaris var. lilacina was extracted with ethanol, and the extract was fractionated to produce the hexane fraction, butanol fraction, chloroform fraction and residual water fraction. The phenolic content was assayed using the Folin-Ciocalteu colorimetric method. Subsequently, the antioxidant activities of the ethanol extract and its fractions were analyzed employing various antioxidant assay methods including DPPH, FRAP, ABTS, SOD activity and production of reactive oxygen species. Additionally, the extract and fractions were assayed for their ability to exert cytotoxic activities on various cancer cells using the MTT assay. We also investigated the expression of genes associated with apoptotic cell death by RT-PCR. The total phenolic contents of the ethanol extract and water fraction of P. vulgaris var. lilacina were 303.66 and 322.80 mg GAE/g dry weight (or fractions), respectively. The results showed that the ethanol extract and the water fraction of P. vulgaris var. lilacina had higher antioxidant content than other solvent fractions, similar to their total phenolic content. Anticancer activity was also tested using the HepG2, HT29, A549, MKN45 and HeLa cancer cell lines. The results clearly demonstrated that the P. vulgaris var. lilacina ethanol extract induced significant cytotoxic effects

  4. Anticancer effect of linalool via cancer-specific hydroxyl radical generation in human colon cancer.

    Science.gov (United States)

    Iwasaki, Kenichi; Zheng, Yun-Wen; Murata, Soichiro; Ito, Hiromu; Nakayama, Ken; Kurokawa, Tomohiro; Sano, Naoki; Nowatari, Takeshi; Villareal, Myra O; Nagano, Yumiko N; Isoda, Hiroko; Matsui, Hirofumi; Ohkohchi, Nobuhiro

    2016-11-28

    To investigate the anticancer mechanisms of the monoterpenoid alcohol linalool in human colon cancer cells. The cytotoxic effect of linalool on the human colon cancer cell lines and a human fibroblast cell line was examined using the WST-8 assay. The apoptosis-inducing effect of linalool was measured using the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay and flow cytometry with Annexin V. Oxidative stress was investigated by staining for diphenyl-1-pyrenylphosphine, which is a cellular lipid peroxidation marker, and electron spin resonance spectroscopy. Sixteen SCID mice xenografted with human cancer cells were randomized into 3 groups for in vivo analysis: control and low-dose and high-dose linalool groups. The control group was administered tap water orally every 3 d. The linalool treatment groups were administered 100 or 200 μg/kg linalool solution orally for the same period. All mice were sacrificed under anesthesia 21 d after tumor inoculation, and tumors and organs were collected for immunohistochemistry using an anti-4-hydroxynonenal antibody. Tumor weights were measured and compared between groups. Linalool induced apoptosis of cancer cells in vitro , following the cancer-specific induction of oxidative stress, which was measured based on spontaneous hydroxyl radical production and delayed lipid peroxidation. Mice in the high-dose linalool group exhibited a 55% reduction in mean xenograft tumor weight compared with mice in the control group ( P Linalool exhibited an anticancer effect via cancer-specific oxidative stress, and this agent has potential for application in colon cancer therapy.

  5. The Effective Role of Hydroxyapatite Based Composites in Anticancer Drug Delivery Systems.

    Science.gov (United States)

    Saber-Samandari, Samaneh; Nezafati, Nader; Saber-Samandari, Saeed

    2016-01-01

    Tumors consist of a heterogeneous population of cancer cells carrying multiple genetic mutations. During the past few decades, efforts have focused on curing cancer using various methods. However, traditional cancer therapies still carry some drawbacks, such as limited application for only a few cancer types, killing of normal cells, poor specificity, and associated toxicity. To overcome these disadvantages, drug-delivery methods that emphasize biomaterials have been developed and applied to optimize cancer treatments. Hydroxyapatite (HAP) is a biocompatible inorganic material that can be applied in biomedical drug-delivery applications. This review discusses the features and properties of HAP that make it an effective biomaterial and provides a comprehensive summary of recent studies in which HAP and composites containing HAP were applied as anticancer drug carriers. We believe that HAP-based composites show great promise for cancer treatment using controlled release of therapeutic agents, leading to enhanced efficiency, selective release of drugs, and prohibition of cancer cell proliferation.

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

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    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%.

  7. 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. © Georg Thieme Verlag KG Stuttgart · New York.

  8. Development of a mouse model for testing therapeutic agents: the anticancer effect of dienogest on endometrial neoplasms.

    Science.gov (United States)

    Saito, Fumitaka; Tashiro, Hironori; Yamaguchi, Munekage; Honda, Ritsuo; Ohba, Takashi; Suzuki, Akira; Katabuchi, Hidetaka

    2016-01-01

    As the number of younger women with endometrial carcinoma has increased, fertility-sparing treatments have received more attention. Although there have been several reports on conservative treatments with progestins for endometrial carcinoma, only medroxyprogesterone acetate (MPA) is available in Japan. Dienogest has been developed as a fourth-generation progestin for treating endometriosis. Because of its high progesterone activity, its antitumor activity has attracted attention. In this study, we investigated the anticancer effect of dienogest on endometrial neoplasms using mouse model of endometrial carcinoma. Pten(loxP/loxP) mice were injected with MPA or dienogest subcutaneously to evaluate the anticancer effect against endometrial neoplasms that developed in the mice. One week after injections, histopathological analyzes were performed. Endometrial neoplasms were found in one of the eight (12.5%) mice from each group treated with either dienogest or MPA. In contrast, they were found in seven of eight (87.5%) mice not treated with progestins. Each progestin treatment showed anticancer activity against endometrial neoplasms that developed in the mice compared to those without treatment. Dienogest and MPA showed potent anticancer activity against endometrial neoplasms in our mouse model. The present study demonstrated that dienogest might be a useful therapeutic agent for human endometrial neoplasms.

  9. Biomaterial-based regional chemotherapy: Local anticancer drug delivery to enhance chemotherapy and minimize its side-effects.

    Science.gov (United States)

    Krukiewicz, Katarzyna; Zak, Jerzy K

    2016-05-01

    Since the majority of anticancer pharmacological agents affect not only cancer tissue but also normal cells, chemotherapy is usually accompanied with severe side effects. Regional chemotherapy, as the alternative version of conventional treatment, leads to the enhancement of the therapeutic efficiency of anticancer drugs and, simultaneously, reduction of toxic effects to healthy tissues. This paper provides an insight into different approaches of local delivery of chemotherapeutics, such as the injection of anticancer agents directly into tumor tissue, the use of injectable in situ forming drug carriers or injectable platforms in a form of implants. The wide range of biomaterials used as reservoirs of anticancer drugs is described, i.e. poly(ethylene glycol) and its copolymers, polyurethanes, poly(lactic acid) and its copolymers, poly(ɛ-caprolactone), polyanhydrides, chitosan, cellulose, cyclodextrins, silk, conducting polymers, modified titanium surfaces, calcium phosphate based biomaterials, silicone and silica implants, as well as carbon nanotubes and graphene. To emphasize the applicability of regional chemotherapy in cancer treatment, the commercially available products approved by the relevant health agencies are presented. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Anti-cancer capacity of plasma-treated PBS: effect of chemical composition on cancer cell cytotoxicity.

    Science.gov (United States)

    Van Boxem, Wilma; Van der Paal, Jonas; Gorbanev, Yury; Vanuytsel, Steven; Smits, Evelien; Dewilde, Sylvia; Bogaerts, Annemie

    2017-11-28

    We evaluate the anti-cancer capacity of plasma-treated PBS (pPBS), by measuring the concentrations of NO 2 - and H 2 O 2 in pPBS, treated with a plasma jet, for different values of gas flow rate, gap and plasma treatment time, as well as the effect of pPBS on cancer cell cytotoxicity, for three different glioblastoma cancer cell lines, at exactly the same plasma treatment conditions. Our experiments reveal that pPBS is cytotoxic for all conditions investigated. A small variation in gap between plasma jet and liquid surface (10 mm vs 15 mm) significantly affects the chemical composition of pPBS and its anti-cancer capacity, attributed to the occurrence of discharges onto the liquid. By correlating the effect of gap, gas flow rate and plasma treatment time on the chemical composition and anti-cancer capacity of pPBS, we may conclude that H 2 O 2 is a more important species for the anti-cancer capacity of pPBS than NO 2 - . We also used a 0D model, developed for plasma-liquid interactions, to elucidate the most important mechanisms for the generation of H 2 O 2 and NO 2 - . Finally, we found that pPBS might be more suitable for practical applications in a clinical setting than (commonly used) plasma-activated media (PAM), because of its higher stability.

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

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    Navneet Kumar Yadav

    2017-01-01

    Full Text Available 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.

  12. Growth inhibitory effect of the Src inhibitor dasatinib in combination with anticancer agents on uterine cervical adenocarcinoma cells.

    Science.gov (United States)

    Takiguchi, Eri; Nishimura, Masato; Mineda, Ayuka; Kawakita, Takako; Abe, Akiko; Irahara, Minoru

    2017-11-01

    Uterine cervical adenocarcinoma has a poor clinical prognosis when compared with squamous cell carcinoma. Therefore, the development of new treatment strategies for uterine cervical adenocarcinoma is necessary. Src is a proto-oncogene that is important in cancer progression. Dasatinib is a Src inhibitor that has been reported to be effective when used in combination with anticancer drugs. The present study aimed to confirm Src expression in human cervical adenocarcinoma cell lines and to determine the mechanism underlying the inhibitory effect of dasatinib on Src signaling in vitro . Western blot analysis was performed to investigate Src expression in cervical adenocarcinoma cell lines (HeLa and TCO-2 cells). The cells were cultured for 48 h with the addition of different concentrations of anticancer drugs (paclitaxel or oxaliplatin). Viable cell count was measured using a colorimetric (WST-1) assay. The concentrations of anticancer agents were fixed according to the results obtained, and the same experiments were performed using the drugs in combination with dasatinib at various concentrations to determine the concentrations that significantly affected the number of viable cells. The presence or absence of apoptosis was investigated using a caspase-3/7 assay. Signal transduction in each cell line was examined using western blotting. Src was activated in the two cell lines, and cell proliferation was significantly suppressed by each anticancer drug in combination with 10 µM dasatinib. Caspase-3/7 activity was also increased and Src signaling was suppressed by each anticancer drug in combination with dasatinib. In conclusion, Src is overexpressed in cervical adenocarcinoma cell lines, and dasatinib inhibits intracellular Src signaling and causes apoptosis. The results of the present study suggest that Src may be targeted in novel therapeutic strategies for cervical adenocarcinoma.

  13. Effects of anticancer drugs on glia-glioma brain tumor model characterized by acoustic impedance microscopy

    Science.gov (United States)

    Soon, Thomas Tiong Kwong; Chean, Tan Wei; Yamada, Hikari; Takahashi, Kenta; Hozumi, Naohiro; Kobayashi, Kazuto; Yoshida, Sachiko

    2017-07-01

    An ultrasonic microscope is a useful tool for observing living tissue without chemical fixation or histochemical processing. Two-dimensional (2D) acoustic impedance microscopy developed in our previous study for living cell observation was employed to visualize intracellular changes. We proposed a brain tumor model by cocultivating rat glial cells and C6 gliomas to quantitatively analyze the effects of two types of anticancer drugs, cytochalasin B (CyB) and temozolomide (TMZ), when they were applied. We reported that CyB treatment (25 µg/ml, T = 90 min) significantly reduced the acoustic impedance of gliomas and has little effect on glial cells. Meanwhile, TMZ treatment (2 mg/ml, T = 90 min) impacted both cells equally, in which both cells’ acoustic impedances were decreased. As CyB targets the actin filament polymerization of the cells, we have concluded that the decrease in acoustic impedance was in fact due to actin filament depolymerization and the data can be quantitatively assessed for future studies in novel drug development.

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

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    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.

  15. Vorinostat enhances the cisplatin-mediated anticancer effects in small cell lung cancer cells.

    Science.gov (United States)

    Pan, Chun-Hao; Chang, Ying-Fang; Lee, Ming-Shuo; Wen, B-Chen; Ko, Jen-Chung; Liang, Sheng-Kai; Liang, Mei-Chih

    2016-11-07

    Vorinostat, a histone deacetylase (HDAC) inhibitor, is a promising agent for cancer therapy. Combining vorinostat with cisplatin may relax the chromatin structure and facilitate the accessibility of cisplatin, thus enhancing its cytotoxicity. Studies have not yet investigated the effects of the combination of vorinostat and cisplatin on small cell lung cancer (SCLC). We first assessed the efficacy of vorinostat with etoposide/cisplatin (EP; triple combination) and then investigated the effects of cotreatment with vorinostat and cisplatin on H209 and H146 SCLC cell lines. The anticancer effects of various combinations were determined in terms of cell viability, apoptosis, cell cycle distribution, and vorinostat-regulated proteins. We also evaluated the efficacy of vorinostat/cisplatin combination in H209 xenograft nude mice. Our data revealed that the triple combination engendered a significant reduction of cell viability and high apoptotic cell death. In addition, vorinostat combined with cisplatin enhanced cell growth inhibition, induced apoptosis, and promoted cell cycle arrest. We observed that the acetylation levels of histone H3 and α-tubulin were higher in combination treatments than in vorinostat treatment alone. Moreover, vorinostat reduced the expression of thymidylate synthase (TS), and TS remained inhibited after cotreament with cisplatin. Furthermore, an in vivo study revealed that the combination of vorinostat and cisplatin significantly inhibited tumor growth in xenograft nude mice (tumor growth inhibition T/C% = 20.5 %). Combined treatments with vorinostat promote the cytotoxicity of cisplatin and induce the expression of vorinostat-regulated acetyl proteins, eventually enhancing antitumor effects in SCLC cell lines. Triple combinations with a low dosage of cisplatin demonstrate similar therapeutic effects. Such triple combinations, if applied clinically, may reduce the undesired adverse effects of cisplatin. The effects of the combination of

  16. Eco-friendly biosynthesis, anticancer drug loading and cytotoxic effect of capped Ag-nanoparticles against breast cancer

    Science.gov (United States)

    Naz, M.; Nasiri, N.; Ikram, M.; Nafees, M.; Qureshi, M. Z.; Ali, S.; Tricoli, A.

    2017-11-01

    The work aimed to prepare silver nanoparticles (Ag-NPs) from silver nitrate and various concentrations of the seed extract ( Setaria verticillata) by a green synthetic route. The chemical and physical properties of the resulting Ag-NPs were investigated by X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectrometry and ultraviolet-visible (UV-Vis) spectrophotometry. Anticancer activity of Ag-NPs (5-20 nm) had dose-dependent cytotoxic effect against breast cancer (MCF7-FLV) cells. The in vitro toxicity was studied on adult earthworms (Lumbricina) resulting in statistically significant ( P < 0.05) inhibition. The prepared NPs were loaded with hydrophilic anticancer drugs (ACD), doxorubicin (DOX) and daunorubicin (DNR), for developing a novel drug delivery carrier having significant adsorption capacity and efficiency to remove the side effects of the medicines effective for leukemia chemotherapy.

  17. Protective effect of Zingiber officinale roscoe against anticancer drug doxorubicin-induced acute nephrotoxicity.

    Science.gov (United States)

    Ajith, T A; Aswathy, M S; Hema, U

    2008-09-01

    Oxidative stress due to abnormal production of reactive oxygen species has been implicated in the nephrotoxicity induced by a commonly used anticancer antibiotic doxorubicin (DXN). The nephroprotective effect of aqueous ethanol extract of Zingiber officinale (200 and 400mg/kg, p.o) was evaluated against doxorubicin-induced (15mg/kg, i.p) acute renal damage in rat. Serum urea and creatinine levels were evaluated as the markers of renal failure. Renal antioxidant status such as activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and level of reduced glutathione (GSH) were determined. Level of lipid peroxidation as equivalents of malondialdehyde (MDA), and glutathione-S-transferase (GST) activity were determined in the kidneys. Serum urea and creatinine levels were reduced in the Z. officinale (200 and 400mg/kg, p.o) plus DXN treated groups. The renal antioxidant enzymes activities such as SOD, CAT GPx, levels of GSH and GST activity were restored and that of MDA declined significantly (pDXN treated group. The nephroprotection is mediated by preventing the DXN-induced decline of renal antioxidant status, and also by increasing the activity of GST.

  18. Anti-cancer effects of Piper nigrum via inducing multiple molecular signaling in vivo and in vitro.

    Science.gov (United States)

    Deng, Yan; Sriwiriyajan, Somchai; Tedasen, Aman; Hiransai, Poonsit; Graidist, Potchanapond

    2016-07-21

    Piper nigrum is widely used as a folk medicine including usage for pain relief, fevers, as well as an anti-cancer agent. However the crude extract of piperine free P. nigrum (PFPE), which inhibits breast cancer, and its mechanisms are still being kept secret. This research aims to elucidate the anti-cancer effects of PFPE and its mechanisms. Anti-cancer effects of PFPE were investigated in N-nitroso-N-methylurea (NMU)-induced mammary tumorigenesis rats and breast cancer cell lines MCF-7 and ZR-75-1. Furthermore, the cancer prevention effects of PFPE were investigated in rats. Western blotting was employed to study protein levels induced by PFPE. PFPE was found to up-regulate p53, and down-regulate estrogen receptor (ER), E-cadherin (E-cad), matrix metalloproteinase 9 (MMP-9), matrix metalloproteinase 2 (MMP-2), c-Myc, and vascular endothelial growth factor (VEGF) levels in breast cancer rats. Moreover, PFPE decreased protein levels of E-cad, c-Myc, and VEGF in MCF-7 cells. These results suggest that PFPE can enhance breast cancer cell response to phytochemicals, then induce cell cycle arrest, and inhibit cancer cell proliferation resulting in tumor size decrease in the PFPE treated group. It further suggests that PFPE may suppress tumor cell invasion, migration, and angiogenesis. In addition, PFPE possessed cancer prevention effects through generation of reactive oxygen species (ROS) to higher cancer cell cellular stress. PFPE may possess anti-cancer and cancer prevention effects; hence, it deserves further investigation as a novel candidate for breast cancer treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Synergistic anticancer effects of andrographolide and paclitaxel against A549 NSCLC cells.

    Science.gov (United States)

    Yuan, Huihui; Sun, Bo; Gao, Feng; Lan, Minbo

    2016-11-01

    Paclitaxel (PTX) is widely used in chemotherapy for cancer treatment; however, it has some serious side effects. Andrographolide (Andro) is a potential cancer therapeutic agent isolated from Andrographis paniculata (Burm. f.) Nees (Acanthaceae). The objective of this study is to evaluate the effects of PTX combined with Andro against A549 cells. The effects of 24-48 h treatment with 0.48-60.75 nM PTX and 5.10-328.0 μM Andro on cellular proliferation, apoptosis, cell cycle and intracellular reactive oxygen species (ROS) were determined by sulphorhodamine B assay, Annexin V-FITC/PI apoptosis detection, PI staining and ROS assay, respectively. Synergy was determined using combination index. The antitumour efficacy of 20 mg/kg PTX with 100 mg/kg Andro was studied in a xenograft murine model. IC 50 value of the PTX combined with Andro against A549 cells was 0.5-7.4 nM, which was significantly lower than that of PTX (15.9 nM). PTX with 10 μM Andro caused (1.22-1.27)-fold apoptosis and 1.7-fold ROS accumulation compared with PTX alone. N-Acetylcysteine, a ROS scavenger, blocked this synergy in vitro. In contrast, G2/M phase cell cycle arrest resulting from PTX was not potentiated by Andro. Moreover, PTX in combination with Andro inhibited the growth of A549 transplanted tumours by 98%. The results indicate that the combination of PTX and Andro exert significant synergistic anticancer effect on A549 cells in vitro and in vivo. The synergy may be the result of the accumulation of ROS. The combination of Andro and PTX represents a potential strategy for the treatment of A549 cells.

  20. Dose calculation of anticancer drugs

    NARCIS (Netherlands)

    Gao, Bo; Klumpen, Heinz-Josef; Gurney, Howard

    2008-01-01

    BACKGROUND: Anticancer drugs are characterized by a narrow therapeutic window and significant inter-patient variability in therapeutic and toxic effects. Current body surface area (BSA)-based dosing fails to standardize systemic anticancer drug exposure and other alternative dosing strategies also

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Hsp90 inhibitor NMS-E973 exerts the anticancer effect against glioblastoma via induction of PUMA-mediated apoptosis.

    Science.gov (United States)

    Sun, Libo; Yang, Shoujun; Chi, Guonan; Jin, Xingyi

    2018-01-01

    Glioblastoma is one of the most aggressive and common malignancies of the central nervous system in humans. Owing to the correlation of high Hsp90 expression with prognosis and clinical pathology features of diverse types of cancer, targeting Hsp90 with small-molecule inhibitors has become a promising anticancer strategy. In this study, we aimed to explore the possibility of anticancer effect of NMS-E973 in giloblastoma and elucidate the mechanism. Cell based MTT assay and colony formation assay were used to detect cell viability. Apoptosis was analyzed by nuclear staining with Hoechst 33258 and Annexin V/propidium iodide staining followed by flow cytometry. Western-blot and RT-PCR were used to detect gene expression. Xenograft assay was used to explore the anticancer effect of NMS-E973 in vivo. We found that NMS-E973 induces apoptosis and inhibits cell growth in glioblastoma cells in cell culture and xenograft models. As a proapoptotic Bcl-2 member, PUMA was induced by NMS-E973 in a p53-dependent manner in glioblastoma in cell culture, thereby inducing apoptosis in glioblastoma cells. Furthermore, PUMA was induced by NMS-E973 treatment in xenograft tumors, and deficiency in PUMA significantly suppressed the antitumor effects of NMS-E973. Our study suggests that PUMA-mediated apoptosis is important for the therapeutic responses of NMS-E973. Induction of PUMA might be a potential biomarker for predicting NMS-E973 responses.

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

    Science.gov (United States)

    Fisher, Monte; Yang, Li-Xi

    2002-01-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Anti-Cancer Effect of IN-2001 in T47D Human Breast Cancer.

    Science.gov (United States)

    Joung, Ki Eun; Min, Kyung Nan; Kim, Dae-Kee; Sheen, Yhun Yhong

    2012-01-01

    Histone deacetylases (HDACs) are enzymes involved in the remodelling of chromatin, and have a key role in the epigenetic regulation of gene expression. Histone deacetylase (HDAC) inhibitors are emerging as an exciting new class of potential anti-cancer agents. In recent years, a number of structurally diverse HDAC inhibitors have been identified and these HDAC inhibitors induce growth arrest, differentiation and/or apoptosis of cancer cells in vitro and in vivo. However, the underlying molecular mechanisms remain unclear. This study aimed at investigating the anti-tumor activity of various HDAC inhibitors, IN-2001, using T47D human breast cancer cells. Moreover, the possible mechanism by which HDAC inhibitors exhibit anti-tumor activity was also explored. In estrogen receptor positive T47D cells, IN-2001, HDAC inhibitor showed anti-proliferative effects in dose-and time-dependent manner. In T47D human breast cancer cells showed anti-tumor activity of IN-2001 and the growth inhibitory effects of IN-2001 were related to the cell cycle arrest and induction of apoptosis. Flow cytometry studies revealed that IN-2001 showed accumulation of cells at G2/M phase. At the same time, IN-2001 treatment time-dependently increased sub-G1 population, representing apoptotic cells. IN-2001-mediated cell cycle arrest was associated with induction of cdk inhibitor expression. In T47D cells, IN-2001 as well as other HDAC inhibitors treatment significantly increased p21(WAF1) and p27(KIP1) expression. In addition, thymidylate synthase, an essential enzyme for DNA replication and repair, was down-regulated by IN-2001 and other HDAC inhibitors in the T47D human breast cancer cells. In summary, IN-2001 with a higher potency than other HDAC inhibitors induced growth inhibition, cell cycle arrest, and eventual apoptosis in human breast cancer possibly through modulation of cell cycle and apoptosis regulatory proteins, such as cdk inhibitors, cyclins, and thymidylate synthase.

  6. The anti-cancer effects of Tualang honey in modulating breast carcinogenesis: an experimental animal study.

    Science.gov (United States)

    Ahmed, Sarfraz; Othman, Nor Hayati

    2017-04-11

    Honey has been shown to have anti-cancer effects, but the mechanism behind these effects is not fully understood. We investigated the role of Malaysian jungle Tualang honey (TH) in modulating the hematological parameters, estrogen, estrogen receptors (ER1) and pro and anti-apoptotic proteins expression in induced breast cancer in rats. Fifty nulliparous female Sprague-Dawley rats were used and grouped as follows: Group 0 (healthy normal rats control), Group 1 (negative control; untreated rats), Groups 2, 3 and 4 received daily doses of 0.2, 1.0 and 2.0 g/kg body weight of TH, respectively. The rats in groups 1, 2, 3, 4 were induced with 80 mg/kg of 1-methyl-1-nitrosourea (MNU). TH treatment in groups 2, 3 and 4 was started one week prior to tumor induction and continued for 120 days. The TH-treated rats had tumors of different physical attributes compared to untreated negative control rats; the tumor progression (mean 75.3 days versus 51.5 days); the incidence (mean 76.6% versus 100%); the multiplicity (mean 2.5 versus 4 tumor masses per rat); the size of tumor mass (mean 0.41 cm versus 1.47 cm [p Honey alleviates breast carcinogenesis through modulation of hematologic, estrogenic and apoptotic activities in this experimental breast cancer animal model. Tualang Honey may be used as a natural 'cancer-alleviating' agent or as a supplement to chemotherapeutic agents.

  7. 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.

  8. 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.

  9. Chemical constituents and anticancer effects of the essential oil from leaves of Xylopia laevigata.

    Science.gov (United States)

    Quintans, Jullyana de S S; Soares, Bruno M; Ferraz, Rosana P C; Oliveira, Allan C A; da Silva, Thanany B; Menezes, Leociley R A; Sampaio, Marília F C; Prata, Ana Paula do N; Moraes, Manoel O; Pessoa, Claudia; Antoniolli, Angelo R; Costa, Emmanoel V; Bezerra, Daniel P

    2013-01-01

    Xylopia laevigata, popularly known as "meiú" and "pindaíba", is a medicinal plant used in the folk medicine of the Brazilian Northeast for several purposes. The chemical constituents of the essential oil from leaves of X. laevigata, collected from wild plants growing at three different sites of the remaining Atlantic forest in Sergipe State (Brazilian Northeast), were analyzed by GC/FID and GC/MS. The effect of the essential oil samples was assessed on tumor cells in culture, as well on tumor growth in vivo. All samples of the essential oil were dominated by sesquiterpene constituents. A total of 44 compounds were identified and quantified. Although some small differences were observed in the chemical composition, the presence of γ-muurolene (0.60-17.99%), δ-cadinene (1.15-13.45%), germacrene B (3.22-7.31%), α-copaene (3.33-5.98%), germacrene D (9.09-60.44%), bicyclogermacrene (7.00-14.63%), and (E)-caryophyllene (5.43-7.98%) were verified as major constituents in all samples of the essential oil. In the in vitro cytotoxic study, the essential oil displayed cytotoxicity to all tumor cell lines tested, with the different samples displaying a similar profile; however, they were not hemolytic or genotoxic. In the in vivo antitumor study, tumor growth inhibition rates were 37.3-42.5%. The treatment with the essential oil did not significantly affect body weight, macroscopy of the organs, or blood leukocyte counts. In conclusion, the essential oil from the leaves of X. laevigata is chemically characterized by the presence of γ-muurolene, δ-cadinene, germacrene B, α-copaene, germacrene D, bicyclogermacrene, and (E)-caryophyllene as major constituents and possesses significant in vitro and in vivo anticancer potential. Georg Thieme Verlag KG Stuttgart · New York.

  10. The Study on Acute Subacute Toxicity and Anti-cancer Effect of K-herbal-acupuncture

    Directory of Open Access Journals (Sweden)

    Kwang-Ho, Kim

    2003-02-01

    Full Text Available Objectives : The purpose of this study was to investigate Acute· Subacute Toxicity and Anti-cancer Effect of K-Herbal-acupuncture in mice and rats. Methods : Balb/c mice were injected intraperitoneally with K- herbal-acupuncture for LD50 and acute toxicity test. Sprague-Dawley rats were injected intraperitoneally with K-herbal-acupuncture for subacute toxicity test. K-Herbal-acupuncture was injected on abdomen of mice with S-180 cancer cell line. Result : 1. LD50 of K-Herbal-acupuncture was limited 4×10-3ml/kg~2×10-3ml/kg by the test. 2. In acute toxicity test, all of mice were down to the moving reflex, but the weight of mice was increased in treatment group, compared with the normal group. (p<0.05 3. In acute toxicity test of serum biochemical values of mice, glucose was increased in treatment II group, total cholesterol was increased both treatments.(p<0.05 4. In subacute toxicity test, the clinical signs of toxication was down to the moving reflex, but it is not severe like acute toxicity test, and observed weight loss at the treatments. 5. In subacute toxicity test, liver weight was decreased compared with the normal group. (p<0.05 6. In subacute toxicity test of complete blood count test (CBC of rat, HCT was decreased in treatments, compared with the normal group.(p<0.05 7. In subacute toxicity test of serum biochemical values of rat, uric acid and triglyceride were decreased, and glucose was increased in treatment groups compared with the control group. (p<0.05 8. Median survival time was increased about 45% in treatment groups compared with the control group.(p<0.05 9. Natural killer cell activity was increased in B16F10 lung cancer model, but it was not in sarcoma-180 abdomen cancer. 10. In interleukin-2 productivity test, treatment groups didn't show significant change in lung cancer and abdomen cancer, compared with the normal group.(p<0.005 11. In making an examination of metastatic cancer with the naked eye, melanoma

  11. Oridonin increases anticancer effects of lentinan in HepG2 human hepatoblastoma cells.

    Science.gov (United States)

    Sun, Zhiqiang; Han, Qinghe; Duan, Liwei; Yuan, Qinghai; Wang, Hui

    2018-02-01

    The aim of the present study was to investigate whether oridonin is able to increase the effects of lentinan (LNT) in HepG2 human hepatoblastoma cells by MTT, flow cytometry, reverse transcription-quantitative polymerase chain reaction and western blot analysis. The in vitro results demonstrated that 20 µg/ml of oridonin was a nontoxic concentration for L02 normal liver cells and HepG2 liver cancer cells. Furthermore, treatment with 0-200 µg/ml LNT was only able to decrease the viability of HepG2 liver cancer cells. The growth inhibitory rate of the LNT-L (100 µg/ml) treatment group was 20.7% and the rate of the LNT-H (200 µg/ml) treatment group was 54.8%. Notably, the growth inhibitory rate of the oridonin + LNT-H group was 84.3%. The highest percentage of apoptotic cells was observed in the oridonin + LNT-H group (20 µg/ml oridonin and 200 µg/ml LNT). The percentage of apoptotic cells in the oridonin + LNT-H group was significantly different from the percentage of apoptotic cells in the LNT-H (26.1%) and the LNT-L (16.8%) groups. Treatment with LNT produced an increase in caspase-3, caspase-9, Bcl-2-like protein 4, p53, p21, nuclear factor κB inhibitor-α mRNA and protein expression and a decrease in B-cell lymphoma 2 and nuclear factor-κB expression in HepG2 cells compared with untreated control cells. Treatment with a combination of oridonin and LNT-H induced a further increase in expression with the biggest differences in expression observed between the oridonin + LNT-H group and control. It was observed that treatment with oridonin was able to increase the anticancer effects of LNT in HepG2 cells. Therefore, oridonin may be used to sensitize cells to LNT.

  12. Anticancer effects of different seaweeds on human colon and breast cancers.

    Science.gov (United States)

    Moussavou, Ghislain; Kwak, Dong Hoon; Obiang-Obonou, Brice Wilfried; Maranguy, Cyr Abel Ogandaga; Dinzouna-Boutamba, Sylvatrie-Danne; Lee, Dae Hoon; Pissibanganga, Ordelia Gwenaelle Manvoudou; Ko, Kisung; Seo, Jae In; Choo, Young Kug

    2014-09-24

    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.

  13. Hsp90 inhibitor NMS-E973 exerts the anticancer effect against glioblastoma via induction of PUMA-mediated apoptosis

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    Sun L

    2018-03-01

    Full Text Available Libo Sun,1 Shoujun Yang,2 Guonan Chi,1 Xingyi Jin1 1First Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changhun, Jilin, People’s Republic of China; 2Department of Rehabilitation, China-Japan Union Hospital of Jilin University, Changhun, Jilin, People’s Republic of China Background: Glioblastoma is one of the most aggressive and common malignancies of the central nervous system in humans. Owing to the correlation of high Hsp90 expression with prognosis and clinical pathology features of diverse types of cancer, targeting Hsp90 with small-molecule inhibitors has become a promising anticancer strategy.Purpose: In this study, we aimed to explore the possibility of anticancer effect of NMS-E973 in giloblastoma and elucidate the mechanism.Methods: Cell based MTT assay and colony formation assay were used to detect cell viability. Apoptosis was analyzed by nuclear staining with Hoechst 33258 and Annexin V/propidium iodide staining followed by flow cytometry. Western-blot and RT-PCR were used to detect gene expression. Xenograft assay was used to explore the anticancer effect of NMS-E973 in vivo.Results: We found that NMS-E973 induces apoptosis and inhibits cell growth in glioblastoma cells in cell culture and xenograft models. As a proapoptotic Bcl-2 member, PUMA was induced by NMS-E973 in a p53-dependent manner in glioblastoma in cell culture, thereby inducing apoptosis in glioblastoma cells. Furthermore, PUMA was induced by NMS-E973 treatment in xenograft tumors, and deficiency in PUMA significantly suppressed the antitumor effects of NMS-E973.Conclusion: Our study suggests that PUMA-mediated apoptosis is important for the therapeutic responses of NMS-E973. Induction of PUMA might be a potential biomarker for predicting NMS-E973 responses. Keywords: NMS-E973, PUMA, glioblastoma, apoptosis

  14. Flavonoids from each of the six structural groups reactivate BRM, a possible cofactor for the anticancer effects of flavonoids

    Science.gov (United States)

    Kahali, Bhaskar; Marquez, Stefanie B.; Thompson, Kenneth W.; Yu, Jinlong; Gramling, Sarah J.B.; Lu, Li; Aponick, Aaron; Reisman, David

    2014-01-01

    Flavonoids have been extensively studied and are well documented to have anticancer effects, but it is not entirely known how they impact cellular mechanisms to elicit these effects. In the course of this study, we found that a variety of different flavonoids readily restored Brahma (BRM) in BRM-deficient cancer cell lines. Flavonoids from each of the six different structural groups were effective at inducing BRM expression as well as inhibiting growth in these BRM-deficient cancer cells. By blocking the induction of BRM with shRNA, we found that flavonoid-induced growth inhibition was BRM dependent. We also found that flavonoids can restore BRM functionality by reversing BRM acetylation. In addition, we observed that an array of natural flavonoid-containing products both induced BRM expression as well as deacetylated the BRM protein. We also tested two of the BRM-inducing flavonoids (Rutin and Diosmin) at both a low and a high dose on the development of tumors in an established murine lung cancer model. We found that these flavonoids effectively blocked development of adenomas in the lungs of wild-type mice but not in that of BRMnull mice. These data demonstrate that BRM expression and function are regulated by flavonoids and that functional BRM appears to be a prerequisite for the anticancer effects of flavonoids both in vitro and in vivo. PMID:24876151

  15. Oridonin enhances in vitro anticancer effects of lentinan in SMMC-7721 human hepatoma cells through apoptotic genes

    OpenAIRE

    Xu, Tao; Jin, Fa; Wu, Keren; Ye, Zhipeng; Li, Ning

    2017-01-01

    The aim of the present study was to determine the ability of oridonin to enhance the anticancer activity of lentinan (LNT) in SMMC-7721 human hepatoma cells in vitro by using various techniques, including MTT, flow cytometry, quantitative PCR and western blot assays. The results demonstrated that 20 µg/ml was a non-toxic concentration of oridonin for L02 normal liver cells and SMMC-7721 cells, while 0–200 µg/ml of LNT only had anti-proliferative effects on SMMC-7721 cells. LNT at 100 and 200 ...

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

    Science.gov (United States)

    Cao, Jianhua; Han, Jie; Xiao, Hao; Qiao, Jinping; Han, Mei

    2016-12-14

    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.

  17. Anticancer Effects of the Marine SpongeLipastrotethyasp. Extract on Wild-Type and p53 Knockout HCT116 Cells.

    Science.gov (United States)

    Choi, Kiheon; Lim, Hyun Kyung; Oh, Sung Ryong; Chung, Woo-Hyun; Jung, Joohee

    2017-01-01

    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.

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

    Science.gov (United States)

    Choi, Kiheon; Lim, Hyun Kyung; Oh, Sung Ryong; Chung, Woo-Hyun

    2017-01-01

    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. PMID:28127380

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Inhibition of transmembrane member 16A calcium-activated chloride channels by natural flavonoids contributes to flavonoid anticancer effects.

    Science.gov (United States)

    Zhang, Xuan; Li, Honglin; Zhang, Huiran; Liu, Yani; Huo, Lifang; Jia, Zhanfeng; Xue, Yucong; Sun, Xiaorun; Zhang, Wei

    2017-07-01

    Natural flavonoids are ubiquitous in dietary plants and vegetables and have been proposed to have antiviral, antioxidant, cardiovascular protective and anticancer effects. Transmembrane member 16A (TMEM16A)-encoded Ca 2+ -activated Cl - channels play a variety of physiological roles in many organs and tissues. Overexpression of TMEM16A is also believed to be associated with cancer progression. Therefore, inhibition of TMEM16A current may be a potential target for cancer therapy. In this study, we screened a broad spectrum of flavonoids for their inhibitory activities on TMEM16A currents. A whole-cell patch technique was used to record the currents. The BrdU assay and transwell technique were used to investigate cell proliferation and migration. At a concentration of 100 μM, 10 of 20 compounds caused significant (>50%) inhibition of TMEM16A currents. The four most potent compounds - luteolin, galangin, quercetin and fisetin - had IC 50 values ranging from 4.5 to 15 μM). To examine the physiological relevance of these findings, we also studied the effects of these flavonoids on endogenous TMEM16A currents in addition to cell proliferation and migration in LA795 cancer cells. Among the flavonoids tested, we detected a highly significant correlation between TMEM16A current inhibition and cell proliferation or reduction of migration. This study demonstrates that flavonoids inhibit TMEM16A currents and suggests that flavonoids could have anticancer effects via this mechanism. © 2017 The British Pharmacological Society.

  2. Synthesis of 2-Substituted Benzothiazole Derivatives and Their In Vitro Anticancer Effects and Antioxidant Activities Against Pancreatic Cancer Cells.

    Science.gov (United States)

    Uremis, Nuray; Uremis, Muhammed Mehdi; Tolun, Fatma Inanc; Ceylan, Mustafa; Doganer, Adem; Kurt, Akif Hakan

    2017-11-01

    Pancreatic cancer is one of the deadliest malignancies characterized by strong resistance to almost all chemotherapeutic agents and radiotherapy. In this study, we aimed to investigate the anticancer effect, enzymatic antioxidant activity [superoxide dismutase (SOD), glutathione peroxidase (GPx)] and total antioxidant capacity (TAC) of synthesized benzothiazole compounds against adenocarcinoma cancer cells (PANC-1). 2-((1S,2S)-2-((E)-4-nitrostyryl)cyclopent-3-en-1-yl)benzo[d]thiazole and 2-((1S,2S)-2-((E)-4-fluorostyryl) cyclopent-3-en-1-yl)benzo[d]thiazole containing 2-substituted benzothiazole group were synthesized in two steps. PANC-1 cells were treated with different concentrations of benzothiazole compounds (5, 25, 50. 75 and 100 μM) for 48 h and their cytotoxicity effects were determined by the MTT assay. To determine whether these compounds induced apoptosis, PANC-1 cells were treated with increasing concentrations of the synthetic products. Our study showed that the synthesized compounds have antiproliferative effects against PANC-1 cells and reduced cell viability. These compounds induced apoptosis of pancreatic cancer cells and at the same time reduced the activity of SOD and GPx and reduced TAC. On the basis of these findings, these synthesized benzothiazole compounds may be considered as a potential therapeutic drug against human PANC-1 cancer cells. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  3. Anticancer Effect and Apoptosis Induction of Cymbopogon citratus Plant on Head and Neck HTB43 Cancer Cell Lines

    International Nuclear Information System (INIS)

    Yen, N.; Zainah Adam; Arapoc, D.J.; Mohamed Zaffar Ali Mohamed Amiroudine; Shafii Khamis

    2016-01-01

    Lemongrass (Cymbopogon citratus) is a major crop in Asia, South and Central America, Africa and other tropical countries. It is commonly used as a culinary herb in Asian cuisine and also as medicinal herb in India. The objective of the present study was to investigate the anticancer effect of Cymbopogon citratus essential oil on human head and neck cancer cell lines. Lemongrass essential oil was obtained from fresh lemongrass leaves using the microwave extractor. The yield of the highly purified oil obtained was 0.62 %. The oil was investigated for its in-vitro cytotoxicity and apoptosis induction against human head and neck HTB43 cancer cell lines. The results showed promising cytotoxic effects with IC 50 value of 15.42 ± 6.10 μg/ ml (HTB43) respectively. In addition, the essential oil has found inducing apoptotic effect within HTB43 cells (25.71 ± 1.43 %). These preliminary results indicated that the oil had apoptosis-based cytotoxicity against head and neck cancer cells. However, further investigations need to be carried out in order to elucidate the anti-cancer properties of the oil. The phytochemicals properties of the active compounds found in the oil also need to be studied. (author)

  4. 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.

  5. 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.

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

    International Nuclear Information System (INIS)

    El-Hossary, E.M.M.

    2010-01-01

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

  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.

    Science.gov (United States)

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

    2016-01-01

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

  9. Anti-cancer effect of Annona Muricata Linn Leaves Crude Extract (AMCE) on breast cancer cell line.

    Science.gov (United States)

    Syed Najmuddin, Syed Umar Faruq; Romli, Muhammad Firdaus; Hamid, Muhajir; Alitheen, Noorjahan Banu; Nik Abd Rahman, Nik Mohd Afizan

    2016-08-24

    Annona muricata Linn which comes from Annonaceae family possesses many therapeutic benefits as reported in previous studies and to no surprise, it has been used in many cultures to treat various ailments including headaches, insomnia, and rheumatism to even treating cancer. However, Annona muricata Linn obtained from different cultivation area does not necessarily offer the same therapeutic effects towards breast cancer (in regards to its bioactive compound production). In this study, anti-proliferative and anti-cancer effects of Annona muricata crude extract (AMCE) on breast cancer cell lines were evaluated. A screening of nineteen samples of Annona muricata from different location was determined by MTT assay on breast cancer cell lines (MCF-7, MDA-MB-231, and 4 T1) which revealed a varied potency (IC50) amongst them. Then, based on the IC50 profile from the anti-proliferative assay, further downward assays such as cell cycle analysis, Annexin V/FITC, AO/PI, migration, invasion, and wound healing assay were performed only with the most potent leaf aqueous extract (B1 AMCE) on 4 T1 breast cancer cell line to investigate its anti-cancer effect. Then, the in vivo anti-cancer study was conducted where mice were fed with extract after inducing the tumor. At the end of the experiment, histopathology of tumor section, tumor nitric oxide level, tumor malondialdehyde level, clonogenic assay, T cell immunophenotyping, and proteome profiler analysis were performed. Annona muricata crude extract samples exhibited different level of cytotoxicity toward breast cancer cell lines. The selected B1 AMCE reduced the tumor's size and weight, showed anti-metastatic features, and induced apoptosis in vitro and in vivo of the 4 T1 cells. Furthermore, it decreased the level of nitric oxide and malondialdehyde in tumor while also increased the level of white blood cell, T-cell, and natural killer cell population. The results suggest that, B1 AMCE is a promising candidate for cancer

  10. Anticancer Effect of Ginger Extract against Pancreatic Cancer Cells Mainly through Reactive Oxygen Species-Mediated Autotic Cell Death.

    Directory of Open Access Journals (Sweden)

    Miho Akimoto

    Full Text Available The extract of ginger (Zingiber officinale Roscoe and its major pungent components, [6]-shogaol and [6]-gingerol, have been shown to have an anti-proliferative effect on several tumor cell lines. However, the anticancer activity of the ginger extract in pancreatic cancer is poorly understood. Here, we demonstrate that the ethanol-extracted materials of ginger suppressed cell cycle progression and consequently induced the death of human pancreatic cancer cell lines, including Panc-1 cells. The underlying mechanism entailed autosis, a recently characterized form of cell death, but not apoptosis or necroptosis. The extract markedly increased the LC3-II/LC3-I ratio, decreased SQSTM1/p62 protein, and enhanced vacuolization of the cytoplasm in Panc-1 cells. It activated AMPK, a positive regulator of autophagy, and inhibited mTOR, a negative autophagic regulator. The autophagy inhibitors 3-methyladenine and chloroquine partially prevented cell death. Morphologically, however, focal membrane rupture, nuclear shrinkage, focal swelling of the perinuclear space and electron dense mitochondria, which are unique morphological features of autosis, were observed. The extract enhanced reactive oxygen species (ROS generation, and the antioxidant N-acetylcystein attenuated cell death. Our study revealed that daily intraperitoneal administration of the extract significantly prolonged survival (P = 0.0069 in a peritoneal dissemination model and suppressed tumor growth in an orthotopic model of pancreatic cancer (P < 0.01 without serious adverse effects. Although [6]-shogaol but not [6]-gingerol showed similar effects, chromatographic analyses suggested the presence of other constituent(s as active substances. Together, these results show that ginger extract has potent anticancer activity against pancreatic cancer cells by inducing ROS-mediated autosis and warrants further investigation in order to develop an efficacious candidate drug.

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

    Directory of Open Access Journals (Sweden)

    McDougall Gordon

    2007-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ki-Rok, Kwon

    2003-06-01

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

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

    Science.gov (United States)

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

    2016-04-01

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

  14. 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

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

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    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.

  17. 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.

  18. (Carboxydiamine)Pt(II) complexes of a combretastatin A-4 analogous chalcone: the influence of the diamine ligand on DNA binding and anticancer effects

    Czech Academy of Sciences Publication Activity Database

    Zoldakova, M.; Biersack, B.; Kostrhunová, Hana; Ahmad, A.; Padhye, S.; Sarkar, F.H.; Schobert, R.; Brabec, Viktor

    2011-01-01

    Roč. 2, č. 6 (2011), s. 493-499 ISSN 2040-2503 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : platinum * DNA binding * anticancer effects Subject RIV: BO - Biophysics Impact factor: 2.800, year: 2011

  19. 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

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

    Science.gov (United States)

    Szarc vel Szic, Katarzyna; Op de Beeck, Ken; Ratman, Dariusz; Wouters, An; Beck, Ilse M; Declerck, Ken; Heyninck, Karen; Fransen, Erik; Bracke, Marc; De Bosscher, Karolien; Lardon, Filip; Van Camp, Guy; Vanden Berghe, Wim

    2014-01-01

    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 in therapy

  1. 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. Copyright 2005 John Wiley & Sons, Ltd.

  2. The impact of quality-of-life data in relative effectiveness assessments of new anti-cancer drugs in European countries.

    Science.gov (United States)

    Kleijnen, Sarah; Leonardo Alves, Teresa; Meijboom, Kim; Lipska, Iga; De Boer, Anthonius; Leufkens, Hubertus G; Goettsch, Wim G

    2017-09-01

    The aim of this study is to investigate the role of health-related quality-of-life (QoL) data in relative effectiveness assessments (REAs) of new anti-cancer drugs across European jurisdictions, during health technology assessment procedures. Comparative analysis of guidelines and publicly available REAs in six European jurisdictions of anti-cancer drugs approved by EMA between 2011 and 2013. Fourteen anti-cancer drugs were included, adding up to 79 REAs. Whilst all guidelines state that QoL is a relevant endpoint to determine the relative effectiveness of new cancer drugs, QoL data were included in only 54% of the 79 reports and their impact on the recommendations was limited. Whilst national guidelines recognize the relevance of QoL to determine the relative effectiveness of new anti-cancer drugs, this is not well-reflected in current assessments. Developing and implementing into REAs specific evidence requirements for QoL data would improve the use of this patient-centred outcome in future reimbursement and pricing decisions.

  3. A marginal anticancer effect of regorafenib on pancreatic carcinoma cells in vitro, ex vivo, and in vivo.

    Science.gov (United States)

    Mayer, Barbara; Karakhanova, Svetlana; Bauer, Nathalie; Liu, Li; Zhu, Yifan; Philippov, Pavel P; Werner, Jens; Bazhin, Alexandr V

    2017-11-01

    Activation of receptor tyrosine kinases is recognized as a hallmark of cancer. Vascular endothelial growth factor (VEGF) and its receptor VEGFR are the prominent players in the induction of tumor neoangiogenesis. Strategies to inhibit VEGF and VEGFR are under intensive investigation in preclinical and clinical settings. Regorafenib is a multikinase inhibitor targeting some VEGFR and other receptor kinases. Preclinical results led to the FDA approval of regorafenib for treatment of metastatic colorectal cancer patients. Effects of this drug in pancreatic ductal adenocarcinoma (PDAC) have not been investigated yet. Gene expression was assessed with real-time PCR analysis. In vitro cell viability, proliferation, apoptosis, necrosis, migration, and invasion of the PDAC cells were assessed after regorafenib treatment. Ex vivo anti-tumor effects of regorafenib were investigated in a spheroid model of PDAC. In vivo anti-tumor effects of the drug were evaluated in a fertilized chicken egg model. In this work, we have demonstrated only a marginal anticancer effect of regorafenib in PDAC in vitro and ex vivo. However, in the egg model of PDAC, this drug reduced tumor volume. Besides, regorafenib is capable of modulating the expression of cancer stem cell (CSC) markers and epithelial-to-mesenchymal transition (EMT) markers on PDAC cells. We found out that effects of regorafenib on the expression of CSC and EMT markers are very heterogeneous and depend obviously on original expression of these markers. We concluded that regorafenib might be a potential drug for PDAC and it should be investigated in future clinical trials.

  4. Chemical composition, antioxidant, antitumor, anticancer and cytotoxic effects of Psidium guajava leaf extracts.

    Science.gov (United States)

    Ashraf, Aisha; Sarfraz, Raja Adil; Rashid, Muhammad Abid; Mahmood, Adeel; Shahid, Muhammad; Noor, Nadia

    2016-10-01

    Context Psidium guajava L. (Myrtaceae) leaves are used in traditional medicines for the treatment of cancer, inflammation and other ailments. Objective The current study explores scientific validation for this traditional medication. Materials and methods We used ferric-reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picryl hydrazil (DPPH) assays to estimate antioxidant activity of P. guajava leaf extracts (methanol, hexane and chloroform). Antitumour and in vivo cytotoxic activities were determined using potato disc assay (PDA) and brine shrimp lethality assay, respectively. Three human carcinoma cell lines (KBM5, SCC4 and U266) were incubated with different doses (10-100 μg/mL) of extracts and the anticancer activity was estimated by MTT assay. NF-κB suppressing activity was determined using electrophoretic mobility shift assay (EMSA). Chemical composition of the three extracts was identified by GC-MS. Total phenolic and flavonoid contents were measured by colorimetric assays. Results and discussions The order of antioxidant activity of three extracts was methanol > chloroform > hexane. The IC50 values ranged from 22.73 to 51.65 μg/mL for KBM5; 22.82 to 70.25 μg/mL for SCC4 and 20.97 to 89.55 μg/mL for U266 cells. The hexane extract exhibited potent antitumour (IC50  value = 65.02 μg/mL) and cytotoxic (LC50  value = 32.18 μg/mL) activities. This extract also completely inhibited the TNF-α induced NF-κB activation in KBM5 cells. GC-MS results showed that pyrogallol, palmitic acid and vitamin E were the major components of methanol, chloroform and hexane extracts. We observed significant (p guajava leaf extracts play a substantial role against cancer and down-modulate inflammatory nuclear factor kB.

  5. 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)

  6. Oxidative Stress Mediates through Apoptosis the Anticancer Effect of Phospho-Nonsteroidal Anti-Inflammatory Drugs: Implications for the Role of Oxidative Stress in the Action of Anticancer AgentsS⃞

    Science.gov (United States)

    Sun, Yu; Huang, Liqun; Mackenzie, Gerardo G.

    2011-01-01

    We assessed the relationship between oxidative stress, cytokinetic parameters, and tumor growth in response to novel phospho-nonsteroidal anti-inflammatory drugs (NSAIDs), agents with significant anticancer effects in preclinical models. Compared with controls, in SW480 colon and MCF-7 breast cancer cells, phospho-sulindac, phospho-aspirin, phospho-flurbiprofen, and phospho-ibuprofen (P-I) increased the levels of reactive oxygen and nitrogen species (RONS) and decreased GSH levels and thioredoxin reductase activity, whereas the conventional chemotherapeutic drugs (CCDs), 5-fluorouracil (5-FU), irinotecan, oxaliplatin, chlorambucil, paclitaxel, and vincristine, did not. In both cell lines, phospho-NSAIDs induced apoptosis and inhibited cell proliferation much more potently than CCDs. We then treated nude mice bearing SW480 xenografts with P-I or 5-FU that had an opposite effect on RONS in vitro. Compared with controls, P-I markedly suppressed xenograft growth, induced apoptosis in the xenografts (8.9 ± 2.7 versus 19.5 ± 3.0), inhibited cell proliferation (52.6 ± 5.58 versus 25.8 ± 7.71), and increased urinary F2-isoprostane levels (10.7 ± 3.3 versus 17.9 ± 2.2 ng/mg creatinine, a marker of oxidative stress); all differences were statistically significant. 5-FU's effects on tumor growth, apoptosis, proliferation, and F2-isoprostane were not statistically significant. F2-isoprostane levels correlated with the induction of apoptosis and the inhibition of cell growth. P-I induced oxidative stress only in the tumors, and its apoptotic effect was restricted to xenografts. Our data show that phospho-NSAIDs act against cancer through a mechanism distinct from that of various CCDs, underscore the critical role of oxidative stress in their effect, and indicate that pathways leading to oxidative stress may be useful targets for anticancer strategies. PMID:21646387

  7. HSP32 (HO-1) inhibitor, copoly(styrene-maleic acid)-zinc protoporphyrin IX, a water-soluble micelle as anticancer agent: In vitro and in vivo anticancer effect.

    Science.gov (United States)

    Fang, Jun; Greish, Khaled; Qin, Haibo; Liao, Long; Nakamura, Hideaki; Takeya, Motohiro; Maeda, Hiroshi

    2012-08-01

    We reported previously the antitumor effect of heme oxygenase-1 (HO-1) inhibition by zinc protoporphyrin IX (ZnPP). ZnPP per se is poorly water soluble and thus cannot be used as anticancer chemotherapeutic. Subsequently, we developed water-soluble micelles of ZnPP using styrene-maleic acid copolymer (SMA), which encapsulated ZnPP (SMA-ZnPP). In this report, the in vitro and in vivo therapeutic effects of SMA-ZnPP are described. In vitro experiments using 11 cultured tumor cell lines and six normal cell lines revealed a remarkable cytotoxicity of SMA-ZnPP against various tumor cells; average IC(50) is about 11.1 μM, whereas the IC(50) to various normal cells is significantly higher, that is, more than 50 μM. In the pharmacokinetic study, we found that SMA-ZnPP predominantly accumulated in the liver tissue after i.v. injection, suggesting its applicability for liver cancer. As expected, a remarkable antitumor effect was achieved in the VX-2 tumor model in the liver of rabbit that is known as one the most difficult tumor models to cure. Antitumor effect was also observed in murine tumor xenograft, that is, B16 melanoma and Meth A fibrosarcoma. Meanwhile, no apparent side effects were found even at the dose of ∼7 times higher concentration of therapeutics dose. These findings suggest a potential of SMA-ZnPP as a tool for anticancer therapy toward clinical development, whereas further investigations are warranted. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Improving the bioavailability and anticancer effect of the PCA-1/ALKBH3 inhibitor HUHS015 using sodium salt.

    Science.gov (United States)

    Mabuchi, Miyuki; Shimizu, Tadashi; Ueda, Masahiro; Sasakawa, Yuka; Nakao, Syuhei; Ueda, Yuko; Kawamura, Akio; Tsujikawa, Kazutake; Tanaka, Akito

    2015-01-01

    Prostate cancer antigen (PCA)-1/AlkB homologue 3 (ALKBH3) has been identified as a clinically significant factor and siRNA of PCA-1 inhibits DU145 proliferation both in vitro and in vivo. HUHS015 ( 1: ), a previous reported PCA-1 small-molecule inhibitor, was also effective without any obvious side-effects or toxicity. The potency of HUHS015, however, is not satisfying. We thought the reason is poor solubility of HUHS015 because insoluble material remained at the injection site after subcutaneous administration. To improve this inhibitor's solubility, we prepared various salts of HUHS015 and examined their solubility, which resulted in the selection of HUHS015 sodium salt ( 2: ) for further studies in vivo. Next, we compared the pharmacokinetics of 1: and 2: via several administration routes. We observed significant improvements in the pharmacokinetic parameters. For example, subcutaneous administration of 2: increased the area under the curve (AUC)0-24 by 8-fold compared to 1 and increased the suppressive effect on the proliferation of DU145 cells in a xenograft model. Copyright © 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

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

    Science.gov (United States)

    Ohta, Shinichi; Nitta, Norihisa; Sonoda, Akinaga; Seko, Ayumi; Tanaka, Toyohiko; Takahashi, Masashi; Takemura, Shizuki; Tabata, Yasuhiko; Murata, Kiyoshi

    2009-12-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Ohta, Shinichi [Department of Radiology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu City, Shiga 520-2192 (Japan)], E-mail: junryuhei@yahoo.co.jp; Nitta, Norihisa; Sonoda, Akinaga; Seko, Ayumi; Tanaka, Toyohiko; Takahashi, Masashi [Department of Radiology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu City, Shiga 520-2192 (Japan); Takemura, Shizuki [Department of Pathology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu City, Shiga (Japan); Tabata, Yasuhiko [Institute for Frontier Medical Sciences, Kyoto University, 53 Kawara-cho Shogoin, Sakyo-ku, Kyoto (Japan); Murata, Kiyoshi [Department of Radiology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu City, Shiga 520-2192 (Japan)

    2009-12-15

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

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

    International Nuclear Information System (INIS)

    Ohta, Shinichi; Nitta, Norihisa; Sonoda, Akinaga; Seko, Ayumi; Tanaka, Toyohiko; Takahashi, Masashi; Takemura, Shizuki; Tabata, Yasuhiko; Murata, Kiyoshi

    2009-01-01

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

  12. Folate Receptor-targeted Bioflavonoid Genistein-loaded Chitosan Nanoparticles for Enhanced Anticancer Effect in Cervical Cancers

    Science.gov (United States)

    Cai, Limei; Yu, Rufen; Hao, Xi; Ding, Xiangcui

    2017-08-01

    In this study, novel folic acid-conjugated chitosan nanoparticle was formulated for specific delivery of bioflavonoid, Genistein (GEN), to the cervical cancer cells. The prepared GEN-loaded chitosan nanoparticles (GCN) and folic acid-conjugated GCN (FGCN) showed smaller size with a controlled drug release profile. FGCN exhibited enhanced internalization potential in HeLa cells than that of GCN. The specific internalization of FGCN was mainly due to the affinity of folic acid (FA) with FRs-α which is present in large numbers in HeLa cells. The results revealed that FGCN has a specific affinity towards HeLa cells that will contribute to the better treatment. Folic acid-tagged nanoformulations exhibited a superior cytotoxic effect compared to that of non-targeted formulations. Consistently, IC50 value of GEN decreased from 33.8 to 14.6 μg/ml when treated with FGCN after 24 h incubation. The apoptosis studies indicated that the FGCN nanoparticles were then either GCN or free GEN in terms of anticancer activity. Overall, results revealed that folate conjugation to the delivery system might have great effect on the survival of cervical cancers that will be beneficial for overall cancer treatment.

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

    Science.gov (United States)

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

    2015-11-01

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

  14. Chlorogenic acid complex (CGA7), standardized extract from green coffee beans exerts anticancer effects against cultured human colon cancer HCT-116 cells

    OpenAIRE

    K. Gouthamchandra; H.V. Sudeep; B.J. Venkatesh; K. Shyam Prasad

    2017-01-01

    Coffee is commonly consumed beverage in the world and it has been suggested to have beneficial effect. Chlorogenic acids (CGAs) are main ingredient of coffee beans which has been extensively used in nutraceuticals and medicine. Recently, various therapeutic effects of chlorogenic acids have been investigated. However, there are limited studies to investigate its anticancer properties. In the present study, we have used chlorogenic acid complex (CGA7) a decaffeinated water soluble green coffee...

  15. Cassia tora L. (Jue-ming-zi) has anticancer activity in TCA8113 cells in vitro and exerts anti-metastatic effects in vivo.

    Science.gov (United States)

    Zhao, Xin; Wang, Qiang; Qian, Yu; Pang, Liang

    2013-03-01

    Cassia tora L. (Jue-ming-zi) is a traditional Chinese medicine widely used in East Asia. The in vitro anticancer effects of Jue-ming-zi were evaluated in TCA8113 human tongue carcinoma cells using a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay. At a concentration of 1.0 mg/ml, Cassia tora L. inhibited the growth of TCA8113 cells by 72%; this inhibiton was greater than that by 0.5 and 0.25 mg/ml Cassia tora L. (43 and 16%, respectively). To elucidate the inhibitory mechanisms underlying the anticancer effect of Cassia tora L. in cancer cells, the expression of genes associated with apoptosis, inflammation and metastasis were measured using RT-PCR and western blot analysis. Cassia tora L. significantly induced apoptosis in cancer cells (PCassia tora L., demonstrating its anti-inflammatory properties. Cassia tora L. also exerted a significant anti-metastatic effect on cancer cells as demonstrated by decreased mRNA expression of matrix metalloprotease (MMP) genes and increased expression of tissue inhibitors of metalloproteinases (TIMPs), and as confirmed by the inhibition of induced tumor metastasis induced in 26-M3.1 colon cells in BALB/c mice. Our results demonstrated that Cassia tora L. exhibited the most potent in vitro anticancer effects, induced apoptosis, had anti-inflammatory activities and exerted in vivo anti-metastatic effects. Additionally, the anticancer, anti-inflammatory and anti-metastatic effects of the higher Cassia tora L. concentrations were stronger compared with those of the lower Cassia tora L. concentrations tested.

  16. Common Peak Approach Using Mass Spectrometry Data Sets for Predicting the Effects of Anticancer Drugs on Breast Cancer

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    Masaru Ushijima

    2007-01-01

    Full Text Available We propose a method for biomarker discovery from mass spectrometry data, improving the common peak approach developed by Fushiki et al. (BMC Bioinformatics, 7:358, 2006. The common peak method is a simple way to select the sensible peaks that are shared with many subjects among all detected peaks by combining a standard spectrum alignment and kernel density estimates. The key idea of our proposed method is to apply the common peak approach to each class label separately. Hence, the proposed method gains more informative peaks for predicting class labels, while minor peaks associated with specifi c subjects are deleted correctly. We used a SELDI-TOF MS data set from laser microdissected cancer tissues for predicting the treatment effects of neoadjuvant therapy using an anticancer drug on breast cancer patients. The AdaBoost algorithm is adopted for pattern recognition, based on the set of candidate peaks selected by the proposed method. The analysis gives good performance in the sense of test errors for classifying the class labels for a given feature vector of selected peak values.

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

    Science.gov (United States)

    Tandon, Pramod Kumar; Khatoon, Sayyada

    2014-01-01

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

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

    Science.gov (United States)

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

    2015-07-04

    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. RKO cells were treated with various concentrations of nucleosides-enriched ethanol extract of Cordyceps militaris for 48 h and cytotoxicity was measured using a CCK-8 assay. Then, xenograft Balb/c nude mice were injected with RKO cells and subsequently orally administered with ethanol extract of Cordyceps militaris every day for 3 weeks to examine the inhibitory effect on tumor growth. Lastly, the effect of Cordyceps militaris on cell cycle as well as apoptosis was measured using flow cytometry. Also, the expression of p53, caspase 9, cleaved caspase-3, cleaved PARP, Bim, Bax, Bak, and Bad were detected using western blot assay. RKO cells were highly susceptible to the ethanol extract of Cordyceps militaris (CME) and the growth of RKO cells-derived tumor was significantly delayed by the treatment of Cordyceps militaris. Cordyceps militaris induced cell cycle arrest in G2/M phase (untreated; 20.5 %, CME 100 μg/ml; 61.67 %, CME 300 μg/ml; 66.33 %) and increased early apoptosis (untreated; 1.01 %, CME 100 μg/ml; 8.48 %, CME 300 μg/ml; 18.07 %). The expression of p53, cleaved caspase 9, cleaved caspase-3, cleaved PARP, Bim, Bak, and Bad were upregulated by the treatment of Cordyceps militaris. Ethanol extract of Cordyceps militaris was highly cytotoxic to human colorectal carcinoma RKO cells and inhibited the growth of tumor in xenograft model. The anti-tumor effect of Cordyceps militaris was associated with an induction of cell cycle arrest and mitochondrial-mediated apoptosis.

  19. Determination of the Relative Efficacy of Eicosapentaenoic Acid and Docosahexaenoic Acid for Anti-Cancer Effects in Human Breast Cancer Models

    Science.gov (United States)

    Mazurak, Vera C.; Damaraju, Sambasivarao

    2017-01-01

    Epidemiological studies have associated high fish oil consumption with decreased risk of breast cancer (BC). n-3 long chain polyunsaturated fatty acids (n-3 LCPUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found in fish and fish oils exert anti-cancer effects. However, few studies have examined the relative efficacy of EPA and DHA alone and in mixtures on BC subtypes. This was the objective of the present review, as this research is a necessity for the translation of findings to human health and disease. The literature suggests that DHA has a greater anti-cancer effect in triple negative BC (TNBC). In estrogen positive (ER+) BC, DHA has a greater effect on cell viability, while both fatty acids have similar effects on apoptosis and proliferation. These effects are associated with preferential uptake of DHA into TNBC lipid rafts and EPA in ER+ BC. EPA:DHA mixtures have anti-cancer activity; however, the ratio of EPA:DHA does not predict the relative incorporation of these two fatty acids into membrane lipids as EPA appears to be preferentially incorporated. In summary, DHA and EPA should be considered separately in the context of BC prevention. The elucidation of optimal EPA:DHA ratios will be important for designing targeted n-3 LCPUFA treatments. PMID:29207553

  20. Teng-Long-Bu-Zhong-Tang, a Chinese herbal formula, enhances anticancer effects of 5--Fluorouracil in CT26 colon carcinoma.

    Science.gov (United States)

    Deng, Shan; Hu, Bing; An, Hong-Mei; Du, Qin; Xu, Ling; Shen, Ke-Ping; Shi, Xiu-Feng; Wei, Meng-Meng; Wu, Yang

    2013-06-08

    Colorectal cancer remains one of the leading causes of cancer death worldwide. Traditional Chinese Medicine (TCM) has played a positive role in colorectal cancer treatment. There is a great need to establish effective herbal formula for colorectal cancer treatment. Based on TCM principles and clinical practices, we have established an eight herbs composed formula for colorectal cancer treatment, which is Teng-Long-Bu-Zhong-Tang (TLBZT). We have demonstrated the anticancer effects of TLBZT against colorectal carcinoma in vitro. In present study, we evaluated the anticancer potential of TLBZT, used alone or in combination with low dose of 5-Fluorouracil (5-Fu), in CT26 colon carcinoma in vivo. CT26 colon carcinoma was established in BALB/c mice and treated with TLBZT, 5-Fu, or TLBZT plus 5-Fu. The tumor volumes were observed. Apoptosis was detected by TUNEL assay. Caspases activities were detected by colorimetric assay. Cell senescence was indentified by senescence β-galactosidase staining. Gene expression and angiogenesis was observed by immunohistochemistry or western blot. TLBZT significantly inhibited CT26 colon carcinoma growth. TLBZT elicited apoptosis in CT26 colon carcinoma, accompanied by Caspase-3, 8, and 9 activation and PARP cleavage, and downregulation of XIAP and Survivin. TLBZT also induced cell senescence in CT26 colon carcinoma, with concomitant upregulation of p16 and p21 and downregulation of RB phosphorylation. In addition, angiogenesis and VEGF expression in CT26 colon carcinoma was significantly inhibited by TLBZT treatment. Furthermore, TLBZT significantly enhanced anticancer effects of 5-Fu in CT26 colon carcinoma. TLBZT exhibited significantly anticancer effect, and enhanced the effects of 5-Fu in CT26 colon carcinoma, which may correlate with induction of apoptosis and cell senescence, and angiogenesis inhibition. The present study provides new insight into TCM approaches for colon cancer treatment that are worth of further study.

  1. 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], p<0.05). The anti-proliferative effects of S. platensis were also shown in vivo, where inhibition of pancreatic cancer growth was evidenced since the third day of treatment (p < 0.05). All tested compounds decreased generation of mitochondrial ROS and glutathione redox status (p = 0.0006; 0.016; and 0.006 for S. platensis, PCB, and chlorophyllin, respectively). In conclusion, S. platensis and its tetrapyrrolic components substantially decreased the proliferation of experimental pancreatic cancer. These data support a chemopreventive role of this edible alga. Furthermore, it seems that dietary supplementation with this alga might enhance systemic pool of tetrapyrroles, known to be higher in subjects with Gilbert syndrome.

  2. Differences in transcription levels among wild, domesticated, and hybrid Atlantic salmon (Salmo salar) from two environments.

    Science.gov (United States)

    Debes, Paul V; Normandeau, Eric; Fraser, Dylan J; Bernatchez, Louis; Hutchings, Jeffrey A

    2012-06-01

    Escaped domesticated individuals can introduce disadvantageous traits into wild populations due to both adaptive differences between population ancestors and human-induced changes during domestication. In contrast to their domesticated counterparts, some endangered wild Atlantic salmon populations encounter during their marine stage large amounts of suspended sediments, which may act as a selective agent. We used microarrays to elucidate quantitative transcriptional differences between a domesticated salmon strain, a wild population and their first-generation hybrids during their marine life stage, to describe transcriptional responses to natural suspended sediments, and to test for adaptive genetic variation in plasticity relating to a history of natural exposure or nonexposure to suspended sediments. We identified 67 genes differing in transcription level among salmon groups. Among these genes, processes related to energy metabolism and ion homoeostasis were over-represented, while genes contributing to immunity and actin-/myosin-related processes were also involved in strain differentiation. Domestic-wild hybrids exhibited intermediate transcription patterns relative to their parents for two-thirds of all genes that differed between their parents; however, genes deviating from additivity tended to have similar levels to those expressed by the wild parent. Sediments induced increases in transcription levels of eight genes, some of which are known to contribute to external or intracellular damage mitigation. Although genetic variation in plasticity did not differ significantly between groups after correcting for multiple comparisons, two genes (metallothionein and glutathione reductase) tended to be more plastic in response to suspended sediments in wild and hybrid salmon, and merit further examination as candidate genes under natural selection. © 2012 Blackwell Publishing Ltd.

  3. The effects of adrenocortical hormone (Dexa-Scheroson) on the side effects of radiotherapy and anti-cancer chemotherapy for cancer of the uterus

    International Nuclear Information System (INIS)

    Saito, Yoshiharu; Tamura, Koreroku; Ohashi, Kazuo; Sakurada, Nobuyoshi

    1975-01-01

    In order to relieve and treat hematopoietic hypofunction and radiation sickness which appear on radiotherapy and anticancer chemotherapy of cancer of the uterus, the effects of the drip intravenous injection of the rapidacting adrenocortical hormone (Dexa-Scheroson) were examined in 37 cases. The drip intravenous injection of 10 mg Dexa-Scheroson was administered for 7-14 days in 32 patients who showed severe leukocytopenia with the white cell count of less than 3,000/mm 3 . In most of the patients (20 among 32 patients) the white (cell) count recovered to above 3,000/mm 3 within 5 days after the injection and within 15 days it occurred in 29 among 32 patients. Dexa-Scheroson was effective in 15 among 19 patients with severe thrombocytopenia (the platelet count was below 10 x 10 4 /mm 3 ). The inhibitory effects of Dexa-Scheroson on thrombocytopenia was smaller than its inhibitory effects on leukocytopenia with delayed appearance. Among 37 patients who received adrenocortical hormones because of the severe hematopoietic hypofunction, 27 patients complained of various symptoms. The effects of Dexa-Scheroson on radiation sickness were examined. In 85% of the patients, Dexa-Scheroson was effective on nausea, vomiting, diarrhea, headache, dizziness, etc. while it was effective on general lassitude and anorexia in only 54% of the patients. It was considered that the combined use of the drip intravenous injection of Dexa-Scheroson during radiotherapy or anticancer chemotherapy for cancer of the uterus is effective because of its great effects on the hematopoietic hypofunction and leukocytopenia. (Saito, K.)

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

    Directory of Open Access Journals (Sweden)

    S Bastani

    2016-03-01

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

  5. Anticancer activity of Amauroderma rude.

    Directory of Open Access Journals (Sweden)

    Chunwei Jiao

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

  6. Anticancer Activity of Amauroderma rude

    Science.gov (United States)

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

    2013-01-01

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

  7. Anticancer Synergy Between Polyphenols

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    Urszula Lewandowska

    2014-01-01

    Full Text Available Chemoprevention has recently gained a new dimension due to the possibility of studying the mechanisms of action of chemopreventive agents at the molecular level. Many compounds have been proved to inhibit early stages of carcinogenesis in experimental models. These compounds include both recognized drugs (such as tamoxifen and nonsteroidal anti-inflammatory drugs and natural constituents of edible and therapeutic plants, particularly polyphenols. Phenolics are characterized by high structural diversity and, consequently, a very broad spectrum of biological activities. They are increasingly looked upon as a valuable alternative or a support for synthetic drugs, as evidenced by a growing number of clinical trials regarding the use of phenolic compounds and polyphenol-rich extracts in chemoprevention and therapy. In the present work, we discuss the effectiveness of natural polyphenols as cancer preventive and therapeutic agents resulting from their synergy with synthetic or semisynthetic anticancer drugs as well as with other phenolic compounds of plant origin.

  8. Adenosine Deaminase Inhibitor EHNA Exhibits a Potent Anticancer Effect Against Malignant Pleural Mesothelioma

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    Yasuhiro Nakajima

    2015-01-01

    Full Text Available Background/Aims: Malignant pleural mesothelioma (MPM is an aggressive malignant tumor and an effective therapy has been little provided as yet. The present study investigated the possibility for the adenosine deaminase (ADA inhibitor EHNA as a target of MPM treatment. Methods: MTT assay, TUNEL staining, monitoring of intracellular adenosine concentrations, and Western blotting were carried out in cultured human MPM cell lines without and with knocking-down ADA. The in vivo effect of EHNA was assessed in mice inoculated with NCI-H2052 MPM cells. Results: EHNA induced apoptosis of human MPM cell lines in a concentration (0.01-1 mM- and treatment time (24-48 h-dependent manner, but such effect was not obtained with another ADA inhibitor pentostatin. EHNA increased intracellular adenosine concentrations in a treatment time (3-9 h-dependent manner. EHNA-induced apoptosis of MPM cells was mimicked by knocking-down ADA, and the effect was neutralized by the adenosine kinase inhibitor ABT-702. EHNA clearly suppressed tumor growth in mice inoculated with NCI-H2052 MPM cells. Conclusion: The results of the present study show that EHNA induces apoptosis of MPM cells by increasing intracellular adenosine concentrations, to convert to AMP, and effectively prevents MPM cell proliferation. This suggests that EHNA may be useful for treatment of the tragic neoplasm MPM.

  9. Anti-cancer effect and the underlying mechanisms of gypenosides on human colorectal cancer SW-480 cells.

    Directory of Open Access Journals (Sweden)

    Han Yan

    Full Text Available BACKGROUND: Gypenosides (Gyp, the main components from Gynostemma pentaphyllum Makino, are widely used in traditional Chinese medicine. The present study aimed to investigate the anti-cancer effect and the underlying mechanisms of Gyp on human colorectal cancer cells SW-480. MATERIALS AND METHODS: The inhibitory effect of Gyp on SW-480 cells was evaluated by MTT assay. Apoptotic cell death was detected by nuclear Hoechst 33342 staining and DNA fragmentation analysis. Apoptosis was analyzed using Annexin V-PE/7-amino-actinomycin D staining. Cell membrane integrity was evaluated with flow cytometry following PI staining. Changes of mitochondrial membrane potential (Δψm were detected through flow cytometry analysis of rhodamine 123 (Rh123. The role of reactive oxygen species (ROS in Gyp induced cell death was investigated by intracellular ROS generation and general ROS scavenger. Wound-healing assay was carried out to investigate Gyp-inhibited migration of SW-480 cells in vitro. Additionally, the alterations in F-actin microfilaments were analyzed by FITC-labeled phalloidin toxin staining and the morphological changes were evaluated under scanning electron microscope (SEM. RESULTS: After the Gyp treatment, the plasma membrane permeability of SW-480 cell was increased, Δψm was decreased significantly, the level of intracellular ROS level was increased, DNA fragmentation and apoptotic morphology were observed. Cells treated with Gyp exert serious microfilament network collapse as well as the significant decrease in the number of microvilli. Gyp induced the changes of cell viability, cell migration, intracellular ROS generation and nuclear morphology were alleviated obviously by NAC. CONCLUSION: The results in this study implied that ROS play an important role in Gyp induced cell toxicity and apoptosis, and the mitochondria damage may be upstream of ROS generation post Gyp treatment. The findings of the present study provide new evidences for anti

  10. Analysis of the antiproliferative effects of 3-deazaneoplanocin A in combination with standard anticancer agents in rhabdoid tumor cell lines.

    Science.gov (United States)

    Unland, Rebekka; Borchardt, Christiane; Clemens, Dagmar; Kool, Marcel; Dirksen, Uta; Frühwald, Michael C

    2015-03-01

    Rhabdoid tumors (RTs) are highly aggressive pediatric malignancies with a rather poor prognosis. New therapeutic approaches and optimization of already established treatment protocols are urgently needed. The histone methyltransferase enhancer of zeste homolog 2 (EZH2) is highly overexpressed in RTs and associated strongly with epigenetic silencing in cancer. EZH2 is involved in aggressive cell growth and stem cell maintenance. Thus, EZH2 is an attractive therapeutic target in RTs. The aim of the study presented here was to analyze the effects of a pharmacological inhibition of EZH2 alone and in combination with other anticancer drugs on RTs cells in vitro. The antitumor activity of the S-adenosyl-homocysteine-hydrolase inhibitor 3-deazaneplanocin A (DZNep) alone and in combination with conventional cytostatic drugs (doxorubicin, etoposide) or epigenetic active compounds [5-Aza-CdR, suberoylanilide hydroxamic acid (SAHA)] was assessed by MTT cell proliferation assays on three RT cell lines (A204, BT16, G401). Combinatorial treatment with DZNep synergistically and significantly enhanced the antiproliferative activity of etoposide, 5-Aza-CdR, and SAHA. In functional analyses, pretreatment with DZNep significantly increased the effects of 5-Aza-CdR and SAHA on apoptosis, cell cycle progression, and clonogenicity. Microarray analyses following sequential treatment with DZNep and 5-Aza-CdR or SAHA showed changes in global gene expression affecting apoptosis, neuronal development, and metabolic processes. In-vitro analyses presented here show that pharmacological inhibition of EZH2 synergistically affects the antitumor activity of the epigenetic active compounds 5-Aza-CdR and SAHA. Sequential treatment with these drugs combined with DZNep may represent a new therapeutic approach in RTs.

  11. The anti-cancer effect of octagon and spherical silver nanoparticles on MCF-7 breast cancer cell line

    Directory of Open Access Journals (Sweden)

    Mehrdad Khatami

    2017-04-01

    Full Text Available Background: The modern science of nanotechnology is an interdisciplinary science that has contributed to advances in cancer treatment. This study was performed to evaluate the therapeutic effects of biosynthesized silver nanoparticles on breast cancer cell of line MCF-7 in vitro. Methods: This analytical study was performed in Kerman and Bam University of Medical Sciences, Bam City, Kerman Province, Iran from March 2015 to March 2016. Silver nanoparticles suspension was synthesized using palm kernel extract. The resulting silver nanoparticles were studied and characterized. The ultraviolet-visible spectroscopy and transmission electron microscopy used for screening of physicochemical properties. The average particle size of the biosynthesized silver nanoparticles was determined by transmission electron microscopy. The properties of different concentrations of synthesized silver nanoparticles (1 to 3 μg/ml and palm kernel extract (containing the same concentration of the extract was used for the synthesis of silver nanoparticles against MCF-7 human breast cancer cells were determined by MTT assay. MTT is used to assess cell viability as a function of redox potential. Actively respiring cells convert the water-soluble MTT to an insoluble purple formazan. Results: The ultraviolet-visible spectroscopy showed strong absorption peak at 429 nm. The X-ray diffraction (XRD and transmission electron microscopy (TEM images revealed the formation of silver nanoparticles with spherical and octagon shape and sizes in the range between 1-40 nm, with an average size approximately 17 nm. The anti-cancer effect of silver nanoparticles on cell viability was strongly depends on the concentration of silver nanoparticles and greatly decrease with increasing the concentration of silver nanoparticles. The IC50 amount of silver nanoparticle was 2 μg/ml. Conclusion: The biosynthesized silver nanoparticles showed a dose-dependent toxicity against MCF-7 human breast

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

    Directory of Open Access Journals (Sweden)

    Junji Itou

    2015-12-01

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

  13. 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

  14. Glucocorticoids decrease the production of glucagon-like peptide-1 at the transcriptional level in intestinal L-cells.

    Science.gov (United States)

    Sato, Taiki; Hayashi, Hiroto; Hiratsuka, Masahiro; Hirasawa, Noriyasu

    2015-05-05

    Glucocorticoids are widely used as anti-inflammatory or immunosuppressive drugs, but often induce hyperglycemia as a side effect. Glucagon-like peptide-1 (GLP-1) is secreted from intestinal L cells and plays crucial roles in maintaining glucose homeostasis. However, the direct effects of glucocorticoids on the GLP-1 production pathway in L cells remain unclear. We investigated the effects of glucocorticoids on GLP-1 production in vitro and in vivo. In L cell lines, glucocorticoids decreased GLP-1 release and expression of the precursor, proglucagon, at protein and mRNA levels, which were inhibited by mifepristone. The administration of dexamethasone or budesonide to mice significantly decreased the mRNA expression of proglucagon in the ileum and partially decreased glucose-stimulated GLP-1 secretion. Compound A, a dissociated glucocorticoid receptor modulator, did not affect the expression of proglucagon in vitro. These results suggested that glucocorticoids directly reduced GLP-1 production at the transcriptional level in L cells through a glucocorticoid receptor dimerization-dependent mechanism. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. In vitro and in vivo anticancer effects of singly protonated dehydronorcantharidin silver coordination polymer in CT-26 murine colon carcinoma model.

    Science.gov (United States)

    Jin, Xing; Tan, Xuejie; Zhang, Xiumei; Han, Mingyong; Zhao, Yunxue

    2015-10-15

    Silver complexes are active constituents of the metal-based compounds; several studies suggest that silver complexes possess antimicrobial and anticancer properties. We have recently reported that Ag-SP-DNC, a novel silver and singly protonated dehydronorcantharidin complex, triggers oxidative stress-mediated apoptosis of lung cancer cells. In this study, we investigated the anticancer effects of Ag-SP-DNC in CT-26 murine colon carcinoma model. Ag-SP-DNC induced apoptosis of CT-26 cells, together with inhibition of cell proliferation; treatment of CT-26 tumor-bearing mice with Ag-SP-DNC delayed tumor growth. We also explored the mechanism of action of Ag-SP-DNC and found that Ag-SP-DNC treatment of CT-26 cells was associated with high levels of intracellular reactive oxygen species. The further experiments revealed that Ag-SP-DNC-treated cells underwent loss of mitochondrial membrane potential concomitant with intracellular calcium overload and caspase-3 activation. Taken together, our study demonstrates the potent anticancer effects of Ag-SP-DNC to colorectal cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. γ-Tocotrienol upregulates aryl hydrocarbon receptor expression and enhances the anticancer effect of baicalein

    Energy Technology Data Exchange (ETDEWEB)

    Yamashita, Shuya; Baba, Kiwako; Makio, Akiko; Kumazoe, Motofumi; Huang, Yuhui; Lin, I-Chian; Bae, Jaehoon; Murata, Motoki; Yamada, Shuhei; Tachibana, Hirofumi, E-mail: tatibana@agr.kyushu-u.ac.jp

    2016-05-13

    Previous studies have identified biomolecules that mediate the physiological actions of food factors, such as amino acids, vitamins, fatty acids, minerals, plant polyphenols, and lactobacilli, suggesting that our bodies are equipped with an innate system that senses which food factors are required to maintain our health. However, the effects of environmental factors on food factor sensing (FFS) remains largely unknown. Tocotorienols (T3s), which belongs to the vitamin E family, possess several physiological functions, including cholesterol lowering and neuroprotective effects. Here, we investigated the effects of naturally abundant γ-T3 on FFS-related gene expressions in melanoma using a DNA chip. Our results showed that γ-T3 increased the expression level of aryl hydrocarbon receptor (AhR), a sensing molecule to plant polyphenol baicalein. The co-treatment with γ-T3 and baicalein enhanced the anti-proliferative activity of baicalein, accompanied by the downstream events of AhR-activation induced by baicalein. These data suggest that γ-T3 upregulates AhR expression and enhances its sensitivity to baicalein. - Highlights: • γ-T3 upregulated the expression of AhR in mouse melanoma. • Promotion of the binding activity of Sp1 is associated with the increasing effect of γ-T3 on AhR expression. • γ-T3 enhanced the anti-proliferative activity of baicalein that has an AhR ligand activity. • γ-T3 enhanced the inducing activity of baicalein on the expression of AhR target genes.

  17. Synergistic anticancer effects of the 9.2.27PE immunotoxin and ABT-737 in melanoma.

    Directory of Open Access Journals (Sweden)

    Karianne Risberg

    Full Text Available In cancer, combinations of drugs targeting different cellular functions is well accepted to improve tumor control. We studied the effects of a Pseudomonas exotoxin A (PE-based immunotoxin, the 9.2.27PE, and the BH-3 mimetic compound ABT-737 in a panel of melanoma cell lines. The drug combination resulted in synergistic cytotoxicity, and the cell death observed was associated with apoptosis, as activation of caspase-3, inactivation of Poly (ADP-ribose polymerase (PARP and increased DNA fragmentation could be prevented by pre-treatment with caspase and cathepsin inhibitors. We further show that ABT-737 caused endoplasmic reticulum (ER stress with increased GRP78 and phosphorylated eIF2α protein levels. Moreover, treatment with ABT-737 increased the intracellular calcium levels, an effect which was enhanced by 9.2.27PE, which as a single entity drug had minimal effect on calcium release from the ER. In addition, silencing of Mcl-1 by short hairpin RNA (shRNA enhanced the intracellular calcium levels and cytotoxicity caused by ABT-737. Notably, the combination of 9.2.27PE and ABT-737 caused growth delay in a human melanoma xenograft mice model, supporting further investigations of this particular drug combination.

  18. 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.

  19. Access to the substituted benzyl-1,2,3-triazolyl hesperetin derivatives expressing antioxidant and anticancer effects

    Czech Academy of Sciences Publication Activity Database

    Mistry, B.; Patel, Rahul V.; Keum, Y.S.

    2017-01-01

    Roč. 10, č. 2 (2017), s. 157-166 ISSN 1878-5352 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : free-radical method * oxidative stress * hesperidin * prevention * diseases * Hesperidin * Hesperetin * Cycloaddition * Click chemistry * Anticancer * Antioxidant Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Oncology Impact factor: 4.553, year: 2016

  20. Synergistic Anticancer Effects of Silibinin and Chrysin in T47D Breast Cancer Cells

    Science.gov (United States)

    Javan Maasomi, Zahra; Pilehvar Soltanahmadi, Younes; Dadashpour, Mehdi; Alipour, Shahriar; Abolhasani, Somayeh; Zarghami, Nosratollah

    2017-05-01

    Objective: Breast cancer is one of the most significant causes of female cancer death worldwide. Although several chemotherapeutics have been developed to treat this type of cancer, issues remain such as low survival rates and high reoccurrence after chemotherapy and radiotherapy. To explore a chemopreventive approach to enhancing breast cancer treatment efficacy, the antiproliferative effects of a combination of chrysin and silibinin, two herbal substances, in T47D breast cancer cells were assessed. Materials and Methods: Cytotoxicity of the agents singly and in combination was evaluated by MTT assay. Also, qRT-PCR was used to measure the expression levels of hTERT and cyclin D1 genes after 48 h treatment. Results: Cell viability assays revealed that chrysin or silibinin alone inhibited proliferation in a dose and time-dependent manner, and combining the drugs synergistically induced growth inhibition in the breast cancer cell line. The precise nature of this interaction was further analyzed by the median-effect method, where the combination indices (CI) were T47D cell proliferation. qPCR results showed that the drug combination also synergistically down-regulated the mRNA levels of hTERT and cyclin D1 at all used concentrations compared with the drugs used alone after 48 h treatment (P ≤ 0.05). Conclusion: The data provide evidence that synergistic antiproliferative effects of Chrysin and Silibinin are linked to the down-regulation of cyclin D1 and hTERT genes, and suggest that their combination may have therapeutic value in treatment of breast cancer. Creative Commons Attribution License

  1. Anticancer Activity of Tetrahydrocorysamine against Pancreatic ...

    African Journals Online (AJOL)

    MTT) and flow cytometry assays. The effect of TCSM on the expressions of mitochondria-mediated apoptotic proteins were investigated by Western blot assay. Xenograft assay was used to evaluate the anticancer activity of TCSM in vivo.

  2. Preparation, properties and anticancer effects of mixed As4S4/ZnS nanoparticles capped by Poloxamer 407.

    Science.gov (United States)

    Bujňáková, Z; Baláž, M; Zdurienčíková, M; Sedlák, J; Čaplovičová, M; Čaplovič, Ľ; Dutková, E; Zorkovská, A; Turianicová, E; Baláž, P; Shpotyuk, O; Andrejko, S

    2017-02-01

    Arsenic sulfide compounds have a long history of application in a traditional medicine. In recent years, realgar has been studied as a promising drug in cancer treatment. In this study, the arsenic sulfide (As 4 S 4 ) nanoparticles combined with zinc sulfide (ZnS) ones in different molar ratio have been prepared by a simple mechanochemical route in a planetary mill. The successful synthesis and structural properties were confirmed and followed via X-ray diffraction and high-resolution transmission electron microscopy measurements. The morphology of the particles was studied via scanning electron microscopy and transmission electron microscopy methods and the presence of nanocrystallites was verified. For biological tests, the prepared As 4 S 4 /ZnS nanoparticles were further milled in a circulation mill in a water solution of Poloxamer 407 (0.5wt%), in order to cover the particles with this biocompatible copolymer and to obtain stable nanosuspensions with unimodal distribution. The average size of the particles in the nanosuspensions (~120nm) was determined by photon cross-correlation spectroscopy method. Stability of the nanosuspensions was determined via particle size distribution and zeta potential measurements, confirming no physico-chemical changes for several months. Interestingly, with the increasing amount of ZnS in the sample, the stability was improved. The anti-cancer effects were tested on two melanoma cell lines, A375 and Bowes, with promising results, confirming increased efficiency of the samples containing both As 4 S 4 and ZnS nanocrystals. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Anticancer effects of sweet potato protein on human colorectal cancer cells.

    Science.gov (United States)

    Li, Peng-Gao; Mu, Tai-Hua; Deng, Le

    2013-06-07

    To investigate the effects of proteins purified from sweet potato storage roots on human colorectal cancer cell lines. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Hoechst 33258 nuclear staining and Boyden transwell chamber methods were used to determine whether purified sweet potato protein (SPP) from fresh sweet potato roots affected proliferation, migration and invasion, respectively, of human colorectal cancer SW480 cells in vitro. The inhibitory effects of SPP on growth of human colorectal cancer HCT-8 cells intraperitoneally xenografted in nude mice and spontaneous lung metastasis of murine Lewis lung carcinoma 3LL cells subcutaneously transplanted in C57 BL/6 mice were also investigated in vivo. SPP inhibited the proliferation of SW480 cells in a dose-dependent manner, with an IC50 value of 38.732 μmol/L (r (2) = 0.980, P = 0.003) in the MTT assay. Hoechst 33258 nuclear staining further revealed inhibition of cell viability and induction of apoptosis by SPP. The transwell assay disclosed significant reduction in migrated cells/field by 8 μmol/L SPP (8.4 ± 2.6 vs 23.3 ± 5.4, P = 0.031) and invaded cells/field through the ECMatrix by 0.8 μmol/L SPP, compared with the control (25.2 ± 5.2 vs 34.8 ± 6.1, P = 0.038). Both intraperitoneal (ip) and intragastric (ig) administration of SPP led to significant suppression of growth of intraperitoneally inoculated HCT-8 cells in nude mice to 58.0% ± 5.9% (P = 0.037) and 43.5% ± 7.1% (P = 0.004) of the controls, respectively, after 9 d treatment. Bloody ascites additionally disappeared after ip injection of trypsin inhibitor. Notably, ig and ip administration of SPP induced a significant decrease in spontaneous pulmonary metastatic nodule formation in C57 BL/6 mice (21.0 ± 12.3 and 27.3 ± 12.7 nodules/lung vs 42.5 ± 4.5 nodules/lung in controls, respectively, P < 0.05) after 25 d treatment. Moreover, the average weight of primary tumor nodules in the hind leg of mice decreased from

  4. Biological effects of PEMF (Pulsing Electromagnetic Field): An attempt to modify cell resistance to anticancer agents

    Energy Technology Data Exchange (ETDEWEB)

    Pasquinelli, P. (C.R.E.S.A.M., Pisa (Italy)); Petrini, M.; Mattii, L.; Saviozzi, M.; Malvaldi, G. (Univ. of Pisa (Italy)); Galimberti, S. (Scuola di Perfezionamento S. Anna, Pisa (Italy))

    Pulsing Electromagnetic Field (PEMF) effects lead to a modification of the multidrug resistance (MDR) of cells in vitro and in vivo. The murine leukemic doxorubicin-resistant cell line, P388/Dx, subjected to PEMF irradiation in vitro, showed a significant difference in thymidine incorporation when the concentration of doxorubicin reached a level of 1 [mu]g/mL, which corresponds to the inhibition dose 50 (ID[sub 50]). The human lymphoblastic leukemia vinblastine-resistant cell line, CEM/VLB[sub 100], also showed a significant modification under the same experimental conditions at the in vitro ID[sub 50] corresponding to a vinblastine concentration of 100 ng/mL. BDF1 mice transplanted with P388/Dx cells also had an increase in their life span when Doxorubicin was injected intraperitoneally in fractionated doses, while being subjected to PEMF irradiation. 7 refs., 5 figs., 1 tab.

  5. Anti-cancer effects of oncolytic viral therapy combined with photodynamic therapy in human pancreatic cancer cell lines.

    Science.gov (United States)

    Khaled, Yazan S; Wright, Kathleen; Melcher, Alan; Jayne, David

    2015-02-26

    Oncolytic viral therapy and photodynamic therapy are potential therapies for inoperable or advanced pancreatic cancer. Our aim was to investigate the anti-cancer killing effects of reovirus therapy combined with protoporphyrin IX (PpIX)-mediated photodynamic therapy on a variety of human pancreatic cancer cell lines. Pancreatic cancer cell lines (PsPC-1 and BXPC-3) and a non-cancer control cell line (HEK293) were infected with reovirus serotype 3 strain Dearing (T3D) at 0, 0·1, 1, and 10 plaque-forming units (PFU) per cell for 48 h. Cells were incubated with PpIX pro-drug 5-aminolevulinic acid (5-ALA) at 0, 1, 2, 3, and 4 mM for 4 h. Then, cells were photo-irradiated for 15 min with visible red light-emitting diodes with a light-fluence of 0·54 J/cm(2) of 653 nm (PpIX optimal excitation wavelength). The killing effects of reovirus combined with PpIX-mediated photodynamic therapy were analysed in methylthiazoltetrazolium (MTT) and trypan blue assays. The effect of adding reovirus after photodynamic therapy was also assessed. The statistical significance of the difference between groups was assessed with the two-tailed Student's t test. pphotodynamic therapy resulted in a significantly increased cytotoxic effect compared with reovirus monotherapy and photodynamic therapy (p=0·042) with 100% cell death observed across pancreatic cell lines with 10 PFU per cell combined with 1 and 2 mM 5-ALA. There was no difference in cytotoxicity observed between added reovirus before or after photodynamic therapy. To our knowledge, this is the first in-vitro study to combine reovirus oncolytic viral therapy with PpIX-mediated photodynamic therapy to treat pancreatic cancer. These results show a significant additive effect in cell killing and they provide initial evidence for a novel combined therapeutic intervention. National Institute for Health Research. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. 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.

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

    Science.gov (United States)

    Kazłowska, Katarzyna; Lin, Hong-Ting Victor; Chang, Shun-Hsien

    2013-01-01

    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. PMID:24062783

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Andrographolide enhances cisplatin-mediated anticancer effects in lung cancer cells through blockade of autophagy.

    Science.gov (United States)

    Yuwen, Daolu; Mi, Shanwei; Ma, Yuzhu; Guo, Wenjie; Xu, Qiang; Shen, Yan; Shu, Yongqian

    2017-10-01

    Lung cancer is the most common cause of cancer-related death worldwide and the platinum-based drugs such as cisplatin have been used as the first line of the treatment. However, the clinical effectiveness of such chemotherapy is limited by intrinsic or acquired resistance. In this study, we found that cisplatin induced autophagy that attenuated the sensitivity of both A549 and Lewis lung cancer (LLC) cells to cisplatin. In contrast, the clinical drug andrographolide (Andro) suppressed autophagy and enhanced cisplatin-mediated apoptosis in these cells. Using two murine lung cancer models, including a subcutaneously inoculated LLC model and an orthotopic LLC implantation model, we investigated the therapeutic efficacy of the combined treatment of cisplatin and Andro. Compared with the sole cisplatin treatment, combining cisplatin with Andro potentially inhibited tumor growth, reduced the incidence of lung metastases, and relieved renal tubular damage. Moreover, the combined treatment prolonged the life span of tumor-bearing mice. TUNEL and immunohistochemistry assays showed the increase in apoptotic cells and the decrease in both conversion of LC3B-I to LC3B-II and Atg5 protein expression in the tumor tissues from mice with the combined treatment. These results suggest that Andro offers an ideal candidate of autophagy inhibitors in clinical application, and combination of cisplatin with Andro could be a promising strategy for the treatment of lung cancer.

  10. Anticancer effect and feasibility study of hyperthermia treatment of pancreatic cancer using magnetic nanoparticles.

    Science.gov (United States)

    Wang, Lufang; Dong, Jian; Ouyang, Weiwei; Wang, Xiaowen; Tang, Jintian

    2012-03-01

    We investigated the effect and feasibility of hyperthermia treatment on subcutaneous pancreatic cancer in female Kunming mice, using a murine pancreatic cancer cell line (MPC-83) established by us and found in this study to originate from epithelial pancreatic acinus. Magnetic fluid (MF) with ferromagnetic particles of about 20 nm in size was used as a heating mediator. MF was injected into the subcutaneous nodules with subaxillary regions of mice 10 days after tumor transplantation; homogeneous distribution of magnetic nanoparticles in nodules was easily detected by X-ray 24 h later. Mice were allocated to four groups as follows: no treatment (control); MF injection alone; alternating magnetic field (AMF) irradiation alone; and MF injection and hyperthermia generated by applying AMF (300 kHz, 110 Gs). The two hyperthermia-treated subgroup tumors reached central temperatures of 47 and 51˚C, respectively, for 30 min; while rectal temperature in both subgroups remained below 36˚C. Tumor growth was inhibited and survival significantly prolonged in the hyperthermia group compared with other groups (Phyperthermia group apoptosed or necrosed immediately after hyperthermia. By day 14, there were no subcutaneous nodules; and residual magnetic nanoparticles were ingested by phagocytes. Nuclear proliferating cell nuclear antigen (PCNA) decreased in hyperthermia group tumor cells compared to the other groups; cytoplasmic heat shock protein 70 (HSP 70) was conspicuously higher immediately after hyperthermia (P<0.05). This technique had therapeutic potential and provided a new idea in the treatment of pancreatic cancer.

  11. A high quality Arabidopsis transcriptome for accurate transcript-level analysis of alternative splicing

    KAUST Repository

    Zhang, Runxuan

    2017-04-05

    Alternative splicing generates multiple transcript and protein isoforms from the same gene and thus is important in gene expression regulation. To date, RNA-sequencing (RNA-seq) is the standard method for quantifying changes in alternative splicing on a genome-wide scale. Understanding the current limitations of RNA-seq is crucial for reliable analysis and the lack of high quality, comprehensive transcriptomes for most species, including model organisms such as Arabidopsis, is a major constraint in accurate quantification of transcript isoforms. To address this, we designed a novel pipeline with stringent filters and assembled a comprehensive Reference Transcript Dataset for Arabidopsis (AtRTD2) containing 82,190 non-redundant transcripts from 34 212 genes. Extensive experimental validation showed that AtRTD2 and its modified version, AtRTD2-QUASI, for use in Quantification of Alternatively Spliced Isoforms, outperform other available transcriptomes in RNA-seq analysis. This strategy can be implemented in other species to build a pipeline for transcript-level expression and alternative splicing analyses.

  12. [Early monitoring of BCR-ABL transcript levels and cytogenetic in assessing the prognosis of chronic myeloid leukemia].

    Science.gov (United States)

    Huang, Qin; Zhang, Xiao-yan; Li, Yan; Wang, Xiao-min

    2013-10-15

    To explore the prognostic significance of early monitoring of BCR-ABL transcript levels and cytogenetic evaluations for chronic myeloid leukemia in chronic phase (CML-CP). From July 2007 to May 2012, 56 CML-CP patients received oral imatinib 400 mg/d. The BCR-ABL transcript levels were monitored and cytogenetic examinations performed after 3 and 6 months respectively. The median follow-up time was 48 months. The 3-month BCR-ABL transcript levels ≤ 10% of patients 5-year overall survival (OS) and progression-free survival (PFS) were better than BCR-ABL transcript levels >10% of patients (OS: 100% vs 84.6%, P = 0.011; PFS: 94.6% vs 67.7%, P = 0.045); cytogenetics: Ph(+) ≤ 35 % of patients 5-year OS and PFS better than Ph(+) > 35% of patients (OS: 100% vs 76.2%, P = 0.001; PFS: 95.2% vs 38.1%, P = 0.001); the 6-month BCR-ABL transcripts level ≤ 1% of patients 5-year OS and PFS also better than BCR-ABL transcript levels> 1% of patients (OS: 100% vs 71.4%, P = 0.000; PFS: 95.2% vs 47.6%, P = 0.001); Ph(+) = 0% and Ph(+)> 0% patients, 5-year OS and PFS were significantly different (OS: 100% vs 68.6%, P = 0.000; PFS: 95.3% vs 45.7%, P = 0.000). Early molecular biology and cytogenetics monitoring have some significance in the prognostic assessment of CML-CP. And individualized treatment strategies should be based upon the monitoring results in conjunctions with comprehensive judgments.

  13. Anticancer effect of ethanol Lycium barbarum (Goji berry) extract on human breast cancer T47D cell line.

    Science.gov (United States)

    Wawruszak, Anna; Czerwonka, Arkadiusz; Okła, Karolina; Rzeski, Wojciech

    2016-09-01

    The anticancer activity of ethanol extract isolated from Goji berry (EEGB) on T47D human breast cancer cell line has been reported. Cell viability and cell proliferation were examined with the use of BrdU, MTT and NR methods. Induction of apoptosis was assessed by propidium iodide and Hoechst 33342 staining. Expression of genes involved in cell proliferation, apoptosis, cell cycle control and regulation of transcription was estimated using Western blotting analysis. EEGB inhibited the proliferation of breast cancer cells in a time-, and dose-dependent manner. The study confirmed the lack of EEGB cytotoxic activity to normal human skin fibroblasts. Western blot analysis demonstrated an increase in pro-apoptotic and a decrease in anti-apoptotic proteins' expression in cells treated with the extract. Anticancer activity and lack of toxicity against normal cells indicate a chemopreventive potential of Goji berries in breast cancer treatment.

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

    Directory of Open Access Journals (Sweden)

    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

  15. Acupuncture as anticancer treatment?

    Directory of Open Access Journals (Sweden)

    Paulina Frączek

    2017-01-01

    Full Text Available 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.

  16. CAR gene cluster and transcript levels of carotenogenic genes in Rhodotorula mucilaginosa.

    Science.gov (United States)

    Landolfo, Sara; Ianiri, Giuseppe; Camiolo, Salvatore; Porceddu, Andrea; Mulas, Giuliana; Chessa, Rossella; Zara, Giacomo; Mannazzu, Ilaria

    2018-01-01

    A molecular approach was applied to the study of the carotenoid biosynthetic pathway of Rhodotorula mucilaginosa. At first, functional annotation of the genome of R. mucilaginosa C2.5t1 was carried out and gene ontology categories were assigned to 4033 predicted proteins. Then, a set of genes involved in different steps of carotenogenesis was identified and those coding for phytoene desaturase, phytoene synthase/lycopene cyclase and carotenoid dioxygenase (CAR genes) proved to be clustered within a region of ~10 kb. Quantitative PCR of the genes involved in carotenoid biosynthesis showed that genes coding for 3-hydroxy-3-methylglutharyl-CoA reductase and mevalonate kinase are induced during exponential phase while no clear trend of induction was observed for phytoene synthase/lycopene cyclase and phytoene dehydrogenase encoding genes. Thus, in R. mucilaginosa the induction of genes involved in the early steps of carotenoid biosynthesis is transient and accompanies the onset of carotenoid production, while that of CAR genes does not correlate with the amount of carotenoids produced. The transcript levels of genes coding for carotenoid dioxygenase, superoxide dismutase and catalase A increased during the accumulation of carotenoids, thus suggesting the activation of a mechanism aimed at the protection of cell structures from oxidative stress during carotenoid biosynthesis. The data presented herein, besides being suitable for the elucidation of the mechanisms that underlie carotenoid biosynthesis, will contribute to boosting the biotechnological potential of this yeast by improving the outcome of further research efforts aimed at also exploring other features of interest.

  17. Lichen Secondary Metabolites in Flavocetraria cucullata Exhibit Anti-Cancer Effects on Human Cancer Cells through the Induction of Apoptosis and Suppression of Tumorigenic Potentials

    Science.gov (United States)

    Nguyen, Thanh Thi; Yoon, Somy; Yang, Yi; Lee, Ho-Bin; Oh, Soonok; Jeong, Min-Hye; Kim, Jong-Jin; Yee, Sung-Tae; Crişan, Florin; Moon, Cheol; Lee, Kwang Youl; Kim, Kyung Keun; Hur, Jae-Seoun; Kim, Hangun

    2014-01-01

    Lichens are symbiotic organisms which produce distinct secondary metabolic products. In the present study, we tested the cytotoxic activity of 17 lichen species against several human cancer cells and further investigated the molecular mechanisms underlying their anti-cancer activity. We found that among 17 lichens species, F. cucullata exhibited the most potent cytotoxicity in several human cancer cells. High performance liquid chromatography analysis revealed that the acetone extract of F. cucullata contains usnic acid, salazinic acid, Squamatic acid, Baeomycesic acid, d-protolichesterinic acid, and lichesterinic acid as subcomponents. MTT assay showed that cancer cell lines were more vulnerable to the cytotoxic effects of the extract than non-cancer cell lines. Furthermore, among the identified subcomponents, usnic acid treatment had a similar cytotoxic effect on cancer cell lines but with lower potency than the extract. At a lethal dose, treatment with the extract or with usnic acid greatly increased the apoptotic cell population and specifically activated the apoptotic signaling pathway; however, using sub-lethal doses, extract and usnic acid treatment decreased cancer cell motility and inhibited in vitro and in vivo tumorigenic potentials. In these cells, we observed significantly reduced levels of epithelial-mesenchymal transition (EMT) markers and phosphor-Akt, while phosphor-c-Jun and phosphor-ERK1/2 levels were only marginally affected. Overall, the anti-cancer activity of the extract is more potent than that of usnic acid alone. Taken together, F. cucullata and its subcomponent, usnic acid together with additional component, exert anti-cancer effects on human cancer cells through the induction of apoptosis and the inhibition of EMT. PMID:25360754

  18. Cassia tora L. (Jue-ming-zi) has anticancer activity in TCA8113 cells in vitro and exerts anti-metastatic effects in vivo

    OpenAIRE

    ZHAO, XIN; WANG, QIANG; QIAN, YU; PANG, LIANG

    2012-01-01

    Cassia tora L. (Jue-ming-zi) is a traditional Chinese medicine widely used in East Asia. The in vitro anticancer effects of Jue-ming-zi were evaluated in TCA8113 human tongue carcinoma cells using a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay. At a concentration of 1.0 mg/ml, Cassia tora L. inhibited the growth of TCA8113 cells by 72%; this inhibiton was greater than that by 0.5 and 0.25 mg/ml Cassia tora L. (43 and 16%, respectively). To elucidate the inhibitory ...

  19. 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. ©2015 American Association for Cancer Research.

  20. The effectiveness of therapeutic patient education on adherence to oral anti-cancer medicines in adult cancer patients in ambulatory care settings: a systematic review.

    Science.gov (United States)

    Arthurs, Gilly; Simpson, Janice; Brown, Andrea; Kyaw, Ohnma; Shyrier, Sharon; Concert, Catherine M

    2015-06-12

    Adherence to oral cancer medicines is a challenge for adult patients with cancer. Education specifically tailored for an individual patient with cancer may improve adherence. Therapeutic patient education when utilized effectively may maximize health outcomes and positively affect the quality of life of adult patients with cancer. Currently, there are no published systematic reviews specific to the effectiveness of therapeutic patient education on improvement of oral anti-cancer medicines adherence in patients with cancer. To synthesize the best available evidence on the effectiveness of therapeutic patient education on adherence to oral anti-cancer medicines in adult cancer patients 18 years and older in an ambulatory care setting. Types of participants: This review considered studies involving adults of any ethnicity, race or gender, aged 18 years or older who were diagnosed with any form of cancer, receiving oral anti-cancer medicines in an ambulatory care setting. Types of intervention(s): This review considered studies on the use of therapeutic patient education as the additional intervention to routine patient education for promoting oral anti-cancer medicine adherence in adult patients with cancer in an ambulatory care setting. Routine patient education was considered as a comparator. Types of outcomes: The outcome considered was adherence to prescribed oral anti-cancer medicines. Types of studies: This review considered experimental and observational studies. The literature search included published and unpublished studies in the English Language from 1953 through August 2014. A search of PubMed, CINAHL, Excerpta Medica Database, Academic Search Premier, Cochrane Library, PsycINFO, and Health Source: Nursing/Academic Edition was conducted using identified keywords and indexed terms across all included databases. A search for grey literature and electronic hand searching of relevant journals was also performed. Two reviewers independently evaluated the

  1. 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 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 embryos. It was concluded from the study that L-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. © 2016 Blackwell Verlag GmbH.

  2. Chlorogenic acid complex (CGA7, standardized extract from green coffee beans exerts anticancer effects against cultured human colon cancer HCT-116 cells

    Directory of Open Access Journals (Sweden)

    K. Gouthamchandra

    2017-09-01

    Full Text Available Coffee is commonly consumed beverage in the world and it has been suggested to have beneficial effect. Chlorogenic acids (CGAs are main ingredient of coffee beans which has been extensively used in nutraceuticals and medicine. Recently, various therapeutic effects of chlorogenic acids have been investigated. However, there are limited studies to investigate its anticancer properties. In the present study, we have used chlorogenic acid complex (CGA7 a decaffeinated water soluble green coffee bean extract to evaluate its cytotoxic effect on human and mouse cancer cell lines by using different approaches. From our results we found CGA7 treatment induces cell death in a dose and time dependent manner in different cancer cell lines. Further, CGA7 induced apoptosis was characterized by DNA fragmentation, PARP-1 cleavage, caspase-9 activation, and down regulation of Bcl-2, an anti-apoptotic protein and up regulation of pro-apoptotic protein BAX. Overall findings indicated that CGA7 complex a potent anticancer molecule found in green coffee beans could be a safe bioactive ingredient for prevention of cancer.

  3. Di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT), an anticancer agent, exerts an anti-inflammatory effect in activated human mast cells.

    Science.gov (United States)

    Nam, Sun-Young; Han, Na-Ra; Yoon, Kyoung Wan; Kim, Hyung-Min; Jeong, Hyun-Ja

    2017-10-01

    Inflammation has been closely associated with the development and progression of cancer. Previously, we reported that mast cells play a critical role in tumor growth. The purpose of this study is to investigate the anti-inflammatory effect of an anticancer agent, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT), on an activated human mast cell line, in this case HMC-1 cells. We evaluated the effect and specific molecular mechanism of Dp44mT on phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI) using HMC-1 cells. Here, we demonstrated that Dp44mT significantly decreased the protein levels of hypoxia-inducible factor-1α and vascular endothelial growth factor without exposing activated HMC-1 cells to any cytotoxicity. In activated mast cells, Dp44mT mitigated the strong production and mRNA expression of inflammatory cytokines, in this case, interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and thymic stromal lymphopoietin, through a blockade of caspase-1 and nuclear factor-κB activities. Furthermore, phosphorylations of the mitogen-activated protein kinase family included in inflammatory signaling cascades were significantly inhibited by a Dp44mT treatment. Overall, our results indicate that the anticancer agent Dp44mT has an anti-inflammatory effect and may be of therapeutic importance for the treatment of mast cell-mediated inflammatory diseases.

  4. Assessment of complex water pollution with heavy metals and Pyrethroid pesticides on transcript levels of metallothionein and immune related genes.

    Science.gov (United States)

    Ghazy, Haneen A; Abdel-Razek, Mohamed A S; El Nahas, Abeer F; Mahmoud, Shawky

    2017-09-01

    Alteration of immunological function of an aquatic organism can be used as an indicator for evaluating the direct effect of exposure to pollutants. The aim of this work is to assess the impact of complex water pollution with special reference to Pyrethroid pesticides and heavy metals on mRNA transcript levels of Metallothionine and some immune related genes of Nile tilapia (Oreochromas Niloticus). Residues of six heavy metals and six Pyrethroid were assessed in water as well as fish tissues at three different sites of Lake Burullus, located at Northern Egypt. Variations of water physicochemical properties associated with different levels of heavy metals at the three different sections were recorded. Tissue residues of Fe, Mn and Zn, Cu, Ni exceed water levels in contrast to elevated water level of Pb. All assessed Pyrethroids are detected in fish tissue samples with higher concentration (3-42 folds) than that found in water samples especially Cypermethrin. Significant down-regulation of expression levels of metallothionein (MT) at the three sections of the lake was observed. The expression of immune related genes (IgM) and inflammatory cytokines (TNF, IL.8 and IL.1) were affected. IgM and TNF were significantly down-regulated at eastern and western section of the lake; meanwhile the expression of IL8 is down regulated at the three sections of the lack. IL1 was significantly up-regulated at eastern and middle sections. We conclude that, variable gene expression of MT and immune-related genes at the three sections of the lack impose different response to complex water pollution in relation to variable aquatic environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Hair Growth Promoting and Anticancer Effects of p21-activated kinase 1 (PAK1 Inhibitors Isolated from Different Parts of Alpinia zerumbet

    Directory of Open Access Journals (Sweden)

    Nozomi Taira

    2017-01-01

    Full Text Available PAK1 (p21-activated kinase 1 is an emerging target for the treatment of hair loss (alopecia and cancer; therefore, the search for PAK1 blockers to treat these PAK1-dependent disorders has received much attention. In this study, we evaluated the anti-alopecia and anticancer effects of PAK1 inhibitors isolated from Alpinia zerumbet (alpinia in cell culture. The bioactive compounds isolated from alpinia were found to markedly promote hair cell growth. Kaempferol-3-O-β-d-glucuronide (KOG and labdadiene, two of the isolated compounds, increased the proliferation of human follicle dermal papilla cells by approximately 117%–180% and 132%–226%, respectively, at 10–100 μM. MTD (2,5-bis(1E,3E,5E-6-methoxyhexa-1,3,5-trien-1-yl-2,5-dihydrofuran and TMOQ ((E-2,2,3,3-tetramethyl-8-methylene-7-(oct-6-en-1-yloctahydro-1H-quinolizine showed growth-promoting activity around 164% and 139% at 10 μM, respectively. The hair cell proliferation induced by these compounds was significantly higher than that of minoxidil, a commercially available treatment for hair loss. Furthermore, the isolated compounds from alpinia exhibited anticancer activity against A549 lung cancer cells with IC50 in the range of 67–99 μM. Regarding the mechanism underlying their action, we hypothesized that the anti-alopecia and anticancer activities of these compounds could be attributed to the inhibition of the oncogenic/aging kinase PAK1.

  6. Fascaplysin Exerts Anti-Cancer Effects through the Downregulation of Survivin and HIF-1α and Inhibition of VEGFR2 and TRKA

    Directory of Open Access Journals (Sweden)

    Taek-In Oh

    2017-09-01

    Full Text Available Fascaplysin has been reported to exert anti-cancer effects by inhibiting cyclin-dependent kinase 4 (CDK4; however, the precise mode of action by which fascaplysin suppresses tumor growth is not clear. Here, we found that fascaplysin has stronger anti-cancer effects than other CDK4 inhibitors, including PD0332991 and LY2835219, on lung cancer cells that are wild-type or null for retinoblastoma (RB, indicating that unknown target molecules might be involved in the inhibition of tumor growth by fascaplysin. Fascaplysin treatment significantly decreased tumor angiogenesis and increased cleaved-caspase-3 in xenografted tumor tissues. In addition, survivin and HIF-1α were downregulated in vitro and in vivo by suppressing 4EBP1-p70S6K1 axis-mediated de novo protein synthesis. Kinase screening assays and drug-protein docking simulation studies demonstrated that fascaplysin strongly inhibited vascular endothelial growth factor receptor 2 (VEGFR2 and tropomyosin-related kinase A (TRKA via DFG-out non-competitive inhibition. Overall, these results suggest that fascaplysin inhibits TRKA and VEGFR2 and downregulates survivin and HIF-1α, resulting in suppression of tumor growth. Fascaplysin, therefore, represents a potential therapeutic approach for the treatment of multiple types of solid cancer.

  7. Inhibitory effects of sizofiran on anticancer agent- or X-ray-induced sister chromatid exchanges and mitotic block in murine bone marrow cells

    International Nuclear Information System (INIS)

    Yang, Zhi-Bo; Tsuchiya, Yoshinori; Arika, Tadashi; Hosokawa, Masuo.

    1993-01-01

    The inhibitory effects of a biological response modifier (RRM), sizofiran, on sister chromatid exchanges (SCEs) in the bone marrow cells of mice treated with various anticancer agents or irradiation were investigated. Sizofiran (10 mg/kg i.m.) inhibited SCEs induced by mitomycin C (2 mg/kg i.v.), adriamycin (20 mg/kg i.v.) and cyclophosphamide (20 mg/kg i.v.) by about 20%, respectively. Analysis of the SCEs in vivo after irradiation plus sizofiran indicated that SCE levels were significantly lower than those observed in mice exposed to irradiation without sizofiran. Moreover, the effects of sizofiran were dependent on the timing of administration. Our results indicated that sizofiran should be administered simultaneously or soon after irradiation in order to minimize damage. Sizofiran also markedly restored the bone marrow cell mitosis which had been suppressed by anticancer agents, and this action was closely correlated with the prevention of increase in SCEs. These results indicate that in addition to immunopotentiating activity, sizofiran may play a role in preventing chromosomal damage induced by cancer chemotherapy and radiotherapy. (author)

  8. Effects of polyamines on the DNA-reactive properties of dimeric mithramycin complexed with cobalt(II): implications for anticancer therapy.

    Science.gov (United States)

    Hou, Ming-Hon; Lu, Wen-Je; Huang, Chun-Yu; Fan, Ruey-Jane; Yuann, Jeu-Ming P

    2009-06-09

    Few studies have examined the effects of polyamines on the action of DNA-binding anticancer drugs. Here, a Co(II)-mediated dimeric mithramycin (Mith) complex, (Mith)(2)-Co(II), was shown to be resistant to polyamine competition toward the divalent metal ion when compared to the Fe(II)-mediated drug complexes. Surface plasmon resonance experiments demonstrated that polyamines interfered with the binding capacity and association rates of (Mith)(2)-Co(II) binding to DNA duplexes, while the dissociation rates were not affected. Although (Mith)(2)-Co(II) exhibited the highest oxidative activity under physiological conditions (pH 7.3 and 37 degrees C), polyamines (spermine in particular) inhibited the DNA cleavage activity of the (Mith)(2)-Co(II) in a concentration-dependent manner. Depletion of intracellular polyamines by methylglyoxal bis(guanylhydrazone) (MGBG) enhanced the sensitivity of A549 lung cancer cells to (Mith)(2)-Co(II), most likely due to the decreased intracellular effect of polyamines on the action of (Mith)(2)-Co(II). Our study suggests a novel method for enhancing the anticancer activity of DNA-binding metalloantibiotics through polyamine depletion.

  9. 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

  10. 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.

  11. 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.

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

    Science.gov (United States)

    Yao, Hong; Chen, Bing; Zhang, Yanyan; Ou, Huigen; Li, Yuxiang; Li, Shaoguang; Shi, Peiying; Lin, Xinhua

    2017-02-20

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Egawa, H.; Maki, A.; Mori, K.; Yamamoto, Y.; Mitsuhashi, S.; Bannai, K.; Asano, K.; Ozawa, K. (Kyoto Univ. (Japan))

    1990-06-01

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

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

    International Nuclear Information System (INIS)

    Feng, Xue; Li, Ling; Jiang, Hong; Jiang, Keping; Jin, Ye; Zheng, Jianhua

    2014-01-01

    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

  15. Metformin inhibited esophageal squamous cell carcinoma proliferation in vitro and in vivo and enhanced the anti-cancer effect of cisplatin.

    Science.gov (United States)

    Wang, Feng; Ding, Xianfei; Wang, Tao; Shan, Zhengzheng; Wang, Jun; Wu, Shaoxuan; Chi, Yanyan; Zhang, Yana; Lv, Zhuan; Wang, Liuxing; Fan, Qingxia

    2017-01-01

    Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with poor prognosis in China. Chemotherapy now is one of the most frequently used treatments for patients with ESCC in middle or late stage, however the effects were often limited by increased chemoresistance or treatment toxicity. So it is urgent to find new drugs to treat ESCC patients. Metformin with low cost and toxicity has proved to have anti-cancer effects in a numerous cancers, while its role and mechanism in ESCC has seldom been studied. In the present study, we found that metformin exhibited not only an anti-proliferation ability in a dose and time dependent manner but also a proapoptosis effect in a dose dependent manner in ESCC cell line KYSE450. Our in vivo experiment also showed that metformin markedly inhibited KYSE450 xenograft tumors growth compared to those treated with normal saline. What's more, no obvious toxic reactions were observed. To further explore the underlying mechanism, we found that metformin treatment could significantly damp the expression of 4EBP1 and S6K1 in KYSE 450 cells in vitro and in vivo, furthermore, the p-4EBP1 and p-S6K1 expression in KYSE 450 cells were also inhibited greatly in vitro and in vivo. During the therapy of cancer, in order to overcome side effects, combination therapy was often used. In this paper, we demonstrated that metformin potentiated the effects of cisplatin via inhibiting cell proliferation and promoting cell apoptosis. Taken together, metformin owned the potential anti-cancer effect on ESCC in monotherapy or was combined with cisplatin and these results laid solid basis for the use of metformin in ESCC.

  16. Metformin inhibited esophageal squamous cell carcinoma proliferation in vitro and in vivo and enhanced the anti-cancer effect of cisplatin.

    Directory of Open Access Journals (Sweden)

    Feng Wang

    Full Text Available Esophageal squamous cell carcinoma (ESCC is an aggressive malignancy with poor prognosis in China. Chemotherapy now is one of the most frequently used treatments for patients with ESCC in middle or late stage, however the effects were often limited by increased chemoresistance or treatment toxicity. So it is urgent to find new drugs to treat ESCC patients. Metformin with low cost and toxicity has proved to have anti-cancer effects in a numerous cancers, while its role and mechanism in ESCC has seldom been studied. In the present study, we found that metformin exhibited not only an anti-proliferation ability in a dose and time dependent manner but also a proapoptosis effect in a dose dependent manner in ESCC cell line KYSE450. Our in vivo experiment also showed that metformin markedly inhibited KYSE450 xenograft tumors growth compared to those treated with normal saline. What's more, no obvious toxic reactions were observed. To further explore the underlying mechanism, we found that metformin treatment could significantly damp the expression of 4EBP1 and S6K1 in KYSE 450 cells in vitro and in vivo, furthermore, the p-4EBP1 and p-S6K1 expression in KYSE 450 cells were also inhibited greatly in vitro and in vivo. During the therapy of cancer, in order to overcome side effects, combination therapy was often used. In this paper, we demonstrated that metformin potentiated the effects of cisplatin via inhibiting cell proliferation and promoting cell apoptosis. Taken together, metformin owned the potential anti-cancer effect on ESCC in monotherapy or was combined with cisplatin and these results laid solid basis for the use of metformin in ESCC.

  17. Development and validation of quantitative PCR assays to measure cytokine transcript levels in the Florida manatee (Trichechus manatus latirostris)

    Science.gov (United States)

    Ferrante, Jason; Hunter, Margaret; Wellehan, James F.X.

    2018-01-01

    Cytokines have important roles in the mammalian response to viral and bacterial infections, trauma, and wound healing. Because of early cytokine production after physiologic stresses, the regulation of messenger RNA (mRNA) transcripts can be used to assess immunologic responses before changes in protein production. To detect and assess early immune changes in endangered Florida manatees (Trichechus manatus latirostris), we developed and validated a panel of quantitative PCR assays to measure mRNA transcription levels for the cytokines interferon (IFN)-γ; interleukin (IL)-2, -6, and -10; tumor necrosis factor-α, and the housekeeping genes glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and β-actin (reference genes). Assays were successfully validated using blood samples from free-ranging, apparently healthy manatees from the east and west coasts of central Florida. No cytokine or housekeeping gene transcription levels were significantly different among age classes or sexes. However, the transcription levels for GAPDH, IL-2, IL-6, and IFN-γ were significantly higher (Pin manatees from the east coast of Florida than they were from those from the west coast. We found IL-10 and β-actin to be consistent between sites and identified β-actin as a good candidate for use as a reference gene in future studies. Our assays can aid in the investigation of manatee immune response to physical trauma and novel or ongoing environmental stressors.

  18. Angiogenic and anti-angiogenic factor gene transcript level quantitation by quantitative real time PCR in patients with hepatocellular carcinoma.

    Science.gov (United States)

    Sharma, Bal Krishan; Srinivasan, Radhika; Kapil, Shweta; Singla, Bhupesh; Chawla, Yogesh Kumar; Chakraborti, Anuradha; Saini, Nitin; Duseja, Ajay; Das, Ashim; Kalra, Naveen; Dhiman, Radha Krishan

    2013-10-01

    Tumor angiogenesis, a major requirement for tumor growth and metastasis, is regulated by pro- and anti-angiogenic factors. The aim of this study was to quantify the expression of angiogenic (VEGF, HIF-1α, Angiopiotein-2) and anti-angiogenic (endostatin, angiostatin and Thrombospondin-1) factors and to discern their clinical relevance. A total 90 patients (67 HCC, 9 cirrhosis and 14 chronic hepatitis) were enrolled in the study. Tissue transcript levels of angiogenic (VEGF, HIF-1α, Ang-2) and anti-angiogenic (endostatin, angiostatin and TSP-1) factors were analyzed by quantitative real time-polymerase chain reaction (qRT-PCR) in the tissue samples. The tissue transcript levels of VEGF, HIF-1α and endostatin were found to be significantly higher in HCC in comparison to cirrhosis and chronic hepatitis. Although Ang-2, angiostatin and TSP-1 tissue transcript levels were higher in HCC group than the others groups but the difference was not statistically significant. In univariate analysis both VEGF and HIF-1α were found to be associated with poor survival of HCC patients. Multivariate analysis by the cox proportional hazard model revealed only VEGF as an independent factor predicting poor survival of the HCC patients. Angiogenic and anti-angiogenic factors are all highly expressed in HCC patients. Upregulation of tissue anti-angiogenic factors indicates the urgency for the alternative of anti-angiogenic therapies.

  19. Development and validation of quantitative PCR assays to measure cytokine transcript levels in the Florida manatee (Trichechus manatus latirostris)

    Science.gov (United States)

    Ferrante, Jason; Hunter, Margaret; Wellehan, James F.X.

    2018-01-01

    Cytokines have important roles in the mammalian response to viral and bacterial infections, trauma, and wound healing. Because of early cytokine production after physiologic stresses, the regulation of messenger RNA (mRNA) transcripts can be used to assess immunologic responses before changes in protein production. To detect and assess early immune changes in endangered Florida manatees (Trichechus manatus latirostris), we developed and validated a panel of quantitative PCR assays to measure mRNA transcription levels for the cytokines interferon (IFN)-γ; interleukin (IL)-2, -6, and -10; tumor necrosis factor-α, and the housekeeping genes glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and β-actin (reference genes). Assays were successfully validated using blood samples from free-ranging, apparently healthy manatees from the east and west coasts of central Florida. No cytokine or housekeeping gene transcription levels were significantly different among age classes or sexes. However, the transcription levels for GAPDH, IL-2, IL-6, and IFN-γ were significantly higher (P<0.05) in manatees from the east coast of Florida than they were from those from the west coast. We found IL-10 and β-actin to be consistent between sites and identified β-actin as a good candidate for use as a reference gene in future studies. Our assays can aid in the investigation of manatee immune response to physical trauma and novel or ongoing environmental stressors.

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

    Directory of Open Access Journals (Sweden)

    Charlotte Soneson

    2016-02-01

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

  1. The potential association of the transcription levels of the ABO gene with the disease phases in AML patients.

    Science.gov (United States)

    Zhang, Wenjing; Liu, Jinling; Zhang, Wei; Zhuang, Yunlong

    2017-10-01

    Patients with AML may show ABO blood typing discrepancy, and the expression levels of the ABO antigens may show some alterations with the disease progression. To better understand this phenomenon, the blood samples of 25 AML patients and 25 healthy blood donors were examined. The serological ABO blood types of the patients were determined in different AML stages, and gene sequencing was performed to identify the precise ABO genotypes. Reverse transcription-polymerase chain reaction (RT-PCR) was carried out to detect the transcription levels of the antigens. The genotyping result showed that there were 4 patients with genotype A 1 O, 5 patients with B 1 O, and 16 patients with A 1 B 1 . RT-PCR results indicated that the transcription levels of the ABO gene in 76% (19/25) of the patients were significantly lower compared with those in controls (p ABO gene from those of controls. The data indicated that the transcription levels of the ABO gene changed with the disease progression, suggesting its potential role in the progression of AML disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Suberoylanilide hydroxamic acid increases anti-cancer effect of tumor necrosis factor-α through up-regulation of TNF receptor 1 in lung cancer cells.

    Science.gov (United States)

    You, Bo Ra; Han, Bo Ram; Park, Woo Hyun

    2017-03-14

    Suberoylanilide hydroxamic acid (SAHA) as a histone deacetylase (HDAC) inhibitor has anti-cancer effect. Here, we evaluated the effect of SAHA on HDAC activity and cell growth in many normal lung and cancer cells. We observed that the HDAC activities of lung cancer cells were higher than that of normal lung cells. SAHA inhibited the growth of lung cancer cells regardless of the inhibitory effect on HDAC. This agent induced a G2/M phase arrest and apoptosis, which was accompanied by mitochondrial membrane potential (MMP: ΔΨm) loss in lung cancer cells. However, SAHA did not induce cell death in normal lung cells. All tested caspase inhibitors prevented apoptotic cell death in SAHA-treated A549 and Calu-6 lung cancer cells. Treatment with tumor necrosis factor-alpha (TNF-α) enhanced apoptosis in SAHA-treated lung cancer cells through caspase-8 and caspase-9 activations. Especially, SAHA increased the expression level of TNF-α receptor 1 (TNFR1), especially acetylation of the region of TNFR1 promoter -223/-29 in lung cancer cells. The down-regulation of TNFR1 suppressed apoptosis in TNF-α and SAHA-treated lung cancer cells. In conclusion, SAHA inhibited the growth of lung cancer cells via a G2/M phase arrest and caspase-dependent apoptosis. SAHA also enhanced apoptotic effect of TNF-α in human lung cancer cells through up-regulation of TNFR1. TNF-α may be a key to improve anti-cancer effect of HDAC inhibitors.

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

    Directory of Open Access Journals (Sweden)

    Yun-Lan Li

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

  4. A novel submicron emulsion system loaded with vincristine–oleic acid ion-pair complex with improved anticancer effect: in vitro and in vivo studies

    Directory of Open Access Journals (Sweden)

    Zhang T

    2013-03-01

    Full Text Available Ting Zhang,1 Yong Zheng,2 iang Peng,3 Xi Cao,1 Tao Gong,1 Zhirong Zhang11Key Laboratory of Drug Targeting and Drug Delivery Systems, Sichuan University, Chengdu, People’s Republic of China; 2Second Affiliated Hospital, Chongqing Medical University, Chongqing, People’s Republic of China; 3State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, People’s Republic of ChinaBackground: Vincristine (VCR, which is a widely used antineoplastic drug, was integrated with a submicron-emulsion drug-delivery system to enhance the anticancer effect.Methods: After the formation of a VCR–oleic acid ion-pair complex (VCR-OA, the VCR-OA-loaded submicron emulsion (VCR-OA-SME, prepared by classical high-pressure homogenization, was characterized and its in vitro anticancer effects were evaluated.Results: The submicron-emulsion formulation exhibited a homogeneous round shape. The mean particle size, zeta potential, and encapsulation efficiency were 157.6 ± 12.6 nm, −26.5 ± 5.0 mV and 78.64% ± 3.44%, respectively. An in vitro release study of the VCR-OA-SME revealed that 12.4% of the VCR was released within the first 2 hours (initial burst-release phase and the rest of the drug was detected in the subsequent sustained-release phase. Compared with VCR solution, the pharmacokinetic study of VCR-OA-SME showed relatively longer mean residence time (mean residence time [0–∞] increased from 187.19 to 227.56 minutes, higher maximum concentration (from 252.13 ng/mL to 533.34 ng/mL, and greater area under the curve (area under the curve [0–∞] from 11,417.77 µg/L/minute to 17,164.34 µg/L/minute. Moreover, the VCR-OA-SME exhibited higher cytotoxicity (P < 0.05 on tumor cells by inducing cell arrest in the G2/M phase or even apoptosis (P < 0.05.Conclusion: The VCR-OA-SME formulation in our study displayed great potential for an anticancer effect for VCR.Keywords: ion-pair complex, submicron emulsion, cytotoxicity, apoptosis, cell uptake

  5. 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.

  6. Combination treatment with dendrosomal nanocurcumin and doxorubicin improves anticancer effects on breast cancer cells through modulating CXCR4/NF-κB/Smo regulatory network.

    Science.gov (United States)

    Mahjoub, Mohammad Amin; Bakhshinejad, Babak; Sadeghizadeh, Majid; Babashah, Sadegh

    2017-08-01

    Despite advantageous antitumor properties of doxorubicin, the considerable cytotoxicity of this chemotherapeutic agent has made it necessary to develop combination treatment strategies. The aim of the current study was to investigate the possible synergism between dendrosomal nanocurcumin (DNC) and doxorubicin in eliciting anticancer effects on MDA-MB-231 metastatic breast cancer cells. The expression levels of CXCL12/CXCR4 axis and Hedgehog pathway genes were evaluated in patient-derived breast carcinoma tissues by qRT-PCR. MTT assay, Annexin V-FITC staining followed by flowcytomety and wound healing assay were used to measure the effects caused by DNC and doxorubicin, alone and in combination, on the viability, apoptosis induction, and migration of MDA-MB-231 cells, respectively. Also, qRT-PCR was exploited to analyze the expression of Smo, NF-κB and CXCR4 in cancer cells. Our results revealed that combination treatment with DNC and doxorubicin leads to significantly decreased viability, increased apoptosis, and reduced migration of breast cancer cells compared with using each drug alone. Also, combination treatment is more efficient that single treatment in reducing the expression levels of NF-κB and Smo transcripts. Our findings provide convincing support for the notion that DNC could synergistically enhance the anticancer effects of doxorubicin on metastatic breast cancer cells by improving its anti-proliferative, pro-apoptotic, and anti-migratory activities. This may be mediated, in part, by downregulating CXCR4, NF-κB, and Smo genes. Overall, the findings of the current study suggest that DNC might be used as a synergistic agent for enhancing therapeutic efficiency and reducing toxic effects of doxorubicin on breast cancer cells.

  7. CancerHSP: anticancer herbs database of systems pharmacology

    Science.gov (United States)

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

    2015-06-01

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

  8. Enhancement of the photo-electric effect with pharmacological agents in synchrotron radiation based anti-cancer radiotherapy: a methodological study

    International Nuclear Information System (INIS)

    Corde, Stephanie

    2002-01-01

    Anti-cancer therapy rests on three main principles: 1) anatomic confinement of irradiation; 2) temporal fractioning of treatment; 3) treatment of tissues that are more sensitive to radiation than surrounding healthy tissue. Under those principles hides the goal of radiotherapy: to deposit more of the X-ray energy in the tumor while preserving the surrounding healthy tissues. This goal is hard to reach since one of the causes of the failures in radiotherapy is the continuing evolution of the tumor. Could synchrotron radiation be more effective as an X-ray source for radiotherapy? The variation of the radiation-matter interaction cross-sections as a function of X-ray energy and atomic number of the medium show that certain energies and certain elements are more suitable to obtain the largest number of interactions and the largest amount of deposited energy. Synchrotron radiation allows to select precisely those energies because of its high spectral intensity. Its spectral characteristics (energy of the photons between 10 and 100 keV) allow to trigger the photoelectric effect with a maximum of probability on heavy elements introduced close to cancerous cells. It has been shown that: 1) synchrotron radiation based tomodensitometry is a quantitative imaging technique, potentially powerful for radiotherapy since it insures in-vivo the measurement of intra-tumoral concentration of contrast agent (I or Gd); 2) in the presence of iodinated contrast agent the lethal effect of X-rays on cell survival is increased and the gain in radio sensitivity depends on X-ray energy; 3) at the cellular scale the lethality of irradiation can be optimised again by transporting heavy atoms (I, Pt) inside the DNA, which is the biological target of the irradiation. This reinforcement of the killing efficiency of low energy X-rays using a physical mechanism aimed at a pharmacological agent is an original concept in anti-cancer radiotherapy. (author) [fr

  9. Quantitative proteomic analysis reveals that anti-cancer effects of selenium-binding protein 1 in vivo are associated with metabolic pathways.

    Science.gov (United States)

    Ying, Qi; Ansong, Emmanuel; Diamond, Alan M; Lu, Zhaoxin; Yang, Wancai; Bie, Xiaomei

    2015-01-01

    Previous studies have shown the tumor-suppressive role of selenium-binding protein 1 (SBP1), but the underlying mechanisms are unclear. In this study, we found that induction of SBP1 showed significant inhibition of colorectal cancer cell growth and metastasis in mice. We further employed isobaric tags for relative and absolute quantitation (iTRAQ) to identify proteins that were involved in SBP1-mediated anti-cancer effects in tumor tissues. We identified 132 differentially expressed proteins, among them, 53 proteins were upregulated and 79 proteins were downregulated. Importantly, many of the differentially altered proteins were associated with lipid/glucose metabolism, which were also linked to Glycolysis, MAPK, Wnt, NF-kB, NOTCH and epithelial-mesenchymal transition (EMT) signaling pathways. These results have revealed a novel mechanism that SBP1-mediated cancer inhibition is through altering lipid/glucose metabolic signaling pathways.

  10. Effectiveness of anticancer drugs determined in nude mice inoculated with [125I]5-iodo-2'-deoxyuridine-prelabeled human melanoma cells

    International Nuclear Information System (INIS)

    Lockshin, A.; Giovanella, B.C.; Vardeman, D.M.; Mendoza, J.T.; Quian, C.; Kozielski, T.; Stehlin, J.S. Jr.

    1985-01-01

    Anticancer drugs were tested on NIH-2 nude mice inoculated ip with BRO human melanoma cells, which are rapidly lethal for these hosts. Criteria for drug activity were a) increased host survival and b) an increased rate of radioactivity loss from mice bearing BRO cells prelabeled with [ 125 I]5-iodo-2'-deoxyuridine. Diphtheria toxin, which is selectively toxic to human cells compared to mouse cells, prolonged host survival and accelerated 125 I elimination in a dose-dependent manner. Drugs that increased the rate of 125 I loss compared to the rate of untreated mice also prolonged the lives of treated mice. With one exception, drugs that did not accelerate 125 I elimination had little or no effect on the length of survival

  11. 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.

  12. Study of small-cell lung cancer cell-based sensor and its applications in chemotherapy effects rapid evaluation for anticancer drugs.

    Science.gov (United States)

    Guohua, Hui; Hongyang, Lu; Zhiming, Jiang; Danhua, Zhu; Haifang, Wan

    2017-11-15

    Small cell lung cancer (SCLC) is a smoking-related cancer disease. Despite improvement in clinical survival, SCLC outcome remains extremely poor. Cisplatin (DDP) is the first-line chemotherapy drug for SCLC, but the choice of second-line chemotherapy drugs is not clear. In this paper, a SCLC cell-based sensor was proposed, and its applications in chemotherapy effects rapid evaluation for anticancer drugs were investigated. SCLC cell lines lung adenocarcinoma cell (LTEP-P) and DDP-resistant lung adenocarcinoma cell (LTEP-P/DDP-1.0) are cultured on carbon screen-printed electrode (CSPE) to fabricate integrated cell-based sensor. Several chemotherapy anticancer drugs, including cisplatin, ifosmamide, gemcitabine, paclitaxel, docetaxel, vinorelbine, etoposide, camptothecin, and topotecan, are selected as experimental chemicals. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) tests are conducted to evaluate chemotherapy drug effects on LTEP-P and LTEP-P/DDP-1.0 cell lines. Electrical cell-substrate impedance sensing (ECIS) responses to anti-tumor chemicals are measured and processed by double-layered cascaded stochastic resonance (DCSR). Cisplatin solutions in different concentrations measurement results demonstrate that LTEP-P cell-based sensor presents quantitative analysis abilities for cisplatin and topotecan. Cisplatin and its mixtures can also be discriminated. Results demonstrate that LTEP-P cell-based sensor sensitively evaluates chemotherapy drugs' apoptosis function to SCLC cells. LTEP-P/DDP-1.0 cell-based sensor responses demonstrate that gemcitabine, vinorelbine, and camptothecin are ideal second-line drugs for clinical post-cisplatin therapy than other drugs according to MTT test results. This work provides a novel way for SCLC second-line clinical chemotherapy drug screening. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    International Nuclear Information System (INIS)

    El shershaby, H.M.M.

    2013-01-01

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

  14. Co-culture with NK-92MI cells enhanced the anti-cancer effect of bee venom on NSCLC cells by inactivation of NF-κB.

    Science.gov (United States)

    Kollipara, Pushpa Saranya; Kim, Jung Hyun; Won, Dohee; Lee, Sang Min; Sung, Ha Chang; Chang, Hyun Sok; Lee, Kang Tae; Lee, Kang Sik; Park, Mi Hee; Song, Min Jong; Song, Ho Sueb; Hong, Jin Tae

    2014-03-01

    In the present study we experimented on a multimodal therapeutic approach, such as combining chemotherapy agent (Bee venom) with cellular (NK-92MI) immunotherapy. Previously bee venom has been found to show anti-cancer effect in various cancer cell lines. In lung cancer cells bee venom showed an IC(50) value of 3 μg/ml in both cell lines. The co-culture of NK-92MI cell lines with lung cancer cells also show a decrease in viability upto 50 % at 48 h time point. Hence we used bee venom treated NK-92MI cells to co-culture with NSCLC cells and found that there is a further decrease in cell viability upto 70 and 75 % in A549 and NCI-H460 cell lines respectively. We further investigated the expression of various apoptotic and anti-apoptotic proteins and found that Bax, cleaved caspase-3 and -8 were increasing where as Bcl-2 and cIAP-2 was decreasing. The expression of various death receptor proteins like DR3, DR6 and Fas was also increasing. Concomitantly the expression of various death receptor ligands (TNFalpha, Apo3L and FasL) was also increasing of NK-92MI cells after co-culture. Further the DNA binding activity and luciferase activity of NF-κB was also inhibited after co-culture with bee venom treated NK-92MI cell lines. The knock down of death receptors with si-RNA has reversed the decrease in cell viability and NF-κB activity after co-culture with bee venom treated NK-92MI cells. Thus this new approach can enhance the anti-cancer effect of bee venom at a much lower concentration.

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

    Science.gov (United States)

    Barbieri, Antonio; Quagliariello, Vincenzo; Del Vecchio, Vitale; Falco, Michela; Luciano, Antonio; Amruthraj, Nagoth Joseph; Nasti, Guglielmo; Ottaiano, Alessandro; Berretta, Massimiliano; Iaffaioli, Rosario Vincenzo; Arra, Claudio

    2017-02-28

    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.

  16. Potent Bivalent Smac Mimetics: Effect of the Linker on Binding to Inhibitor of Apoptosis Proteins (IAPs) and Anticancer Activity

    Science.gov (United States)

    Sun, Haiying; Liu, Liu; Lu, Jianfeng; Bai, Longchuan; Li, Xiaoqin; Nikolovska-Coleska, Zaneta; McEachern, Donna; Yang, Chao-Yie; Qiu, Su; Yi, Han; Sun, Duxin; Wang, Shaomeng

    2011-01-01

    We have synthesized and evaluated a series of non-peptidic, bivalent Smac mimetics as antagonists of the inhibitor of apoptosis proteins and new anticancer agents. All these bivalent Smac mimetics bind to full-length XIAP with low nanomolar affinities and function as ultra-potent antagonists of XIAP. While these Smac mimetics bind to cIAP1/2 with similar low nanomolar affinities, their potencies to induce degradation of cIAP1/2 proteins in cells differ by more than 100-fold. The most potent bivalent Smac mimetics inhibit cell growth with IC50 values from 1–3 nM in the MDA-MB-231 breast cancer cell line and are 100-times more potent than the least potent compounds. Determination of intracellular concentrations for several representative compounds showed that the linkers in these bivalent Smac mimetics significantly affect their intracellular concentrations, hence the overall cellular activity. Compound 27 completely inhibits tumor growth in the MDA-MB-231 xenografts, while causing no signs of toxicity in the animals. PMID:21462933

  17. 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

    2017-03-29

    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.

  18. Toosendanin Exerts an Anti-Cancer Effect in Glioblastoma by Inducing Estrogen Receptor β- and p53-Mediated Apoptosis

    Directory of Open Access Journals (Sweden)

    Liang Cao

    2016-11-01

    Full Text Available Glioblastoma (GBM is the most common primary brain tumor with median survival of approximately one year. This dismal poor prognosis is due to resistance to currently available chemotherapeutics; therefore, new cytotoxic agents are urgently needed. In the present study, we reported the cytotoxicity of toosendanin (TSN in the GBM U87 and C6 cell lines in vitro and in vivo. By using the MTT (3-(4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2-H-tetrazolium bromide assay, flow cytometry analysis, and Western blot, we found that TSN inhibited U87 and C6 cell proliferation and induced apoptosis at a concentration as low as 10 nM. Administration of TSN also reduced tumor burden in a xenograft model of athymic nude mice. Pharmacological and molecular studies suggested that estrogen receptor β (ERβ and p53 were prominent targets for TSN. GBM cell apoptosis induced by TSN was a stepwise biological event involving the upregulation of ERβ and contextual activation of functional p53. Collectively, our study indicates, for the first time, that TSN is a candidate of novel anti-cancer drugs for GBM. Furthermore, ERβ and p53 could act as predictive biomarkers for the sensitivity of cancer to TSN.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. 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.

  1. Sp1 inhibition-mediated upregulation of VEGF 165 b induced by rh-endostatin enhances antiangiogenic and anticancer effect of rh-endostatin in A549.

    Science.gov (United States)

    Li, Zhen-yu; Zhu, Fang; Hu, Jian-li; Peng, Gang; Chen, Jing; Zhang, Sheng; Chen, Xu; Zhang, Rui-guang; Chen, Ling-juan; Liu, Pian; Luo, Ming; Sun, Zhi-hua; Ren, Jing-hua; Huang, Li-li; Wu, Gang

    2011-08-01

    Recombinant human endostatin (rh-endostatin), a potential antiangiogenic agent, is used in non-small cell lung carcinoma treatment and represses vascular endothelial cell growth factor (VEGF) levels in tumor cell. However, precise affection of rh-endostatin on the proangiogenic VEGF isoforms (VEGF(165)) or antiangiogenic VEGF isoforms (VEGF(165)b) is not clear. We therefore tested the hypothesis that rh-endostatin could alter expression of these isoforms to regulate tumor growth. A549 cells were exposed to rh-endostatin, and the expression of VEGF(165) and VEGF(165)b was detected. The role of SP1 as a regulator of isoform expression was investigated. We then examined the anticancer and antiangiogenic efficacy of rh-endostatin in combination with exogenous VEGF(165)b against A549 cells, EA.HY 926 cells and xenograft model of human lung cancer. rh-Endostatin reduced VEGF(165) and induced VEGF(165)b as well as inhibited SP1 in A549 cells. SP1 inhibitor (betulinic acid) also developed those changes. VEGF(165)b-rh-endostatin combination was highly synergistic and inhibited growth, survival, and migration of A549 cells, VEGF-mediated VEGFR2 phosphorylation in EA.HY 926 cells, and tumor growth in xenograft model of human lung cancer. rh-Endostatin downregulates proangiogenic vascular endothelial growth factor A (VEGFA) isoform and upregulates antiangiogenic VEGFA isoform, possibly through inhibition of SP1. Furthermore, VEGF(165)b sensitizes A549 to rh-endostatin treatment and enhances the anticancer effect of rh-endostatin.

  2. Novel ciprofloxacin hybrids using biology oriented drug synthesis (BIODS) approach: Anticancer activity, effects on cell cycle profile, caspase-3 mediated apoptosis, topoisomerase II inhibition, and antibacterial activity.

    Science.gov (United States)

    Kassab, Asmaa E; Gedawy, Ehab M

    2018-03-09

    As we are interested in synthetizing biologically active leads with dual anticancer and antibacterial activity, we adopted biology oriented drug synthesis (BIODS) strategy to synthesize a series of novel ciprofloxacin (CP) hybrids. The National Cancer Institute (USA) selected seventeen newly synthesized compounds for anticancer evaluation against 59 different human tumor cell lines. Five compounds 3e, 3f, 3h, 3o and 3p were further studied through determination of IC 50 values against the most sensitive cancer cell lines. In vitro results showed that the five compounds exhibited potent anticancer activity against test cell lines in nanomolar to micromolar range, with IC 50 values between 0.72 and 4.92 μM, which was 9 to1.5 folds more potent than doxorubicin. In this study, two promising potent anticancer CP hybrids, 3f and 3o, were identified. The anti-proliferative activity of these compounds appears to correlate well with their ability to inhibit Topo II (IC 50  = 0.58 and 0.86 μM). It is worth mentioning that compound 3f was 6 folds more potent than doxorubicin, 5 folds more potent than amsacrine and 1.5 folds more potent than etoposide. At the same time, compound 3o showed 4 folds more inhibitory activity against Topo II than doxorubicin, 3 folds more potent than amsacrine and almost equipotent activity to etoposide. Activation of damage response pathway of the DNA leads to cell cycle arrest at G2/M phase, accumulation of cells in pre-G1 phase and annexin-V and propidium iodide staining, indicating that cell death proceeds through an apoptotic mechanism. Moreover, compounds 3f and 3o showed potent pro-apoptotic effect through induction of the intrinsic mitochondrial pathway of apoptosis. This mechanistic pathway was confirmed by a significant increase in the level of active caspase-3 compared to control. This observation may indicate that both CP hybrids can chelate with zinc, a powerful inhibitor of procaspase-3 enzymatic activity, so procaspase-3

  3. Anticancer and antibacterial secondary metabolites from the ...

    African Journals Online (AJOL)

    Background: The emergence of multiple-drug resistance bacteria has become a major threat and thus calls for an urgent need to search for new effective and safe anti-bacterial agents. Objectives: This study aims to evaluate the anticancer and antibacterial activities of secondary metabolites from Penicillium sp., ...

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

    Directory of Open Access Journals (Sweden)

    Xinbing Sui

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

  5. FLO11 gene length and transcriptional level affect biofilm-forming ability of wild flor strains of Saccharomyces cerevisiae.

    Science.gov (United States)

    Zara, Giacomo; Zara, Severino; Pinna, Claudia; Marceddu, Salvatore; Budroni, Marilena

    2009-12-01

    In Saccharomyces cerevisiae, FLO11 encodes an adhesin that is associated with different phenotypes, such as adherence to solid surfaces, hydrophobicity, mat and air-liquid biofilm formation. In the present study, we analysed FLO11 allelic polymorphisms and FLO11-associated phenotypes of 20 flor strains. We identified 13 alleles of different lengths, varying from 3.0 to 6.1 kb, thus demonstrating that FLO11 is highly polymorphic. Two alleles of 3.1 and 5.0 kb were cloned into strain BY4742 to compare the FLO11-associated phenotypes in the same genetic background. We show that there is a significant correlation between biofilm-forming ability and FLO11 length both in different and in the same genetic backgrounds. Moreover, we propose a multiple regression model that allows prediction of air-liquid biofilm-forming ability on the basis of transcription levels and lengths of FLO11 alleles in a population of S. cerevisiae flor strains. Considering that transcriptional differences are only partially explained by the differences in the promoter sequences, our results are consistent with the hypothesis that FLO11 transcription levels are strongly influenced by genetic background and affect biofilm-forming ability.

  6. Anticancer effects of brominated indole alkaloid Eudistomin H from marine ascidian Eudistoma viride against cervical cancer cells (HeLa).

    Science.gov (United States)

    Rajesh, Rajaian Pushpabai; Annappan, Murugan

    2015-01-01

    Marine invertebrates called ascidians are prolific producers of bioactive substances. The ascidian Eudistoma viride, distributed along the Southeast coast of India, was investigated for its in vitro cytotoxic activity against human cervical carcinoma (HeLa) cells by the MTT assay. The crude methanolic extract of E. viride, with an IC50 of 53 μg/ml, was dose-dependently cytotoxic. It was more potent at 100 μg/ml than cyclohexamide (1 μg/ml), reducing cell viability to 9.2%. Among nine fractions separated by chromatography, ECF-8 exhibited prominent cytoxic activity at 10 μg/ml. The HPLC fraction EHF-21 of ECF-8 was remarkably dose- and time-dependently cytotoxic, with 39.8% viable cells at 1 μg/ml compared to 51% in cyclohexamide-treated cells at the same concentration; the IC50 was 0.49 μg/ml. Hoechst staining of HeLa cells treated with EHF-21 at 0.5 μg/ml revealed apoptotic events such an cell shrinkage, membrane blebbing, chromatin condensation and formation of apoptotic bodies. Cell size and granularity study showed changes in light scatter, indicating the characteristic feature of cells dying by apoptosis. The cell-cycle analysis of HeLa cells treated with fraction EHF-21 at 1 μg/ml showed the marked arrest of cells in G0/G1, S and G2/M phases and an increase in the sub G0/G1 population indicated an increase in the apoptotic cell population. The statistical analysis of the sub-G1 region showed a dose-dependent induction of apoptosis. DNA fragmentation was also observed in HeLa cells treated with EHF-21. The active EHF-21 fraction, a brominated indole alkaloid Eudistomin H, led to apoptotic death of HeLa cells. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Chi Zhang

    2015-01-01

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

  8. Bacteriophages displaying anticancer peptides in combined antibacterial and anticancer treatment.

    Science.gov (United States)

    Dąbrowska, Krystyna; Kaźmierczak, Zuzanna; Majewska, Joanna; Miernikiewicz, Paulina; Piotrowicz, Agnieszka; Wietrzyk, Joanna; Lecion, Dorota; Hodyra, Katarzyna; Nasulewicz-Goldeman, Anna; Owczarek, Barbara; Górski, Andrzej

    2014-01-01

    Novel anticancer strategies have employed bacteriophages as drug carriers and display platforms for anticancer agents; however, bacteriophage-based platforms maintain their natural antibacterial activity. This study provides the assessment of combined anticancer (engineered) and antibacterial (natural) phage activity in therapies. An in vivo BALB/c mouse model of 4T1 tumor growth accompanied by surgical wound infection was applied. The wounds were located in the areas of tumors. Bacteriophages (T4) were modified with anticancer Tyr-Ile-Gly-Ser-Arg (YIGSR) peptides by phage display and injected intraperitoneally. Tumor growth was decreased in mice treated with YIGSR-displaying phages. The acuteness of wounds, bacterial load and inflammatory markers in phages-treated mice were markedly decreased. Thus, engineered bacteriophages combine antibacterial and anticancer activity.

  9. The cre-inducer doxycycline lowers cytokine and chemokine transcript levels in the gut of mice

    DEFF Research Database (Denmark)

    Hansen, Axel Kornerup; Malm, Sara Astrup; Metzdorff, Stine B.

    2017-01-01

    The antibiotic doxycycline is used as an inducer of recombinase (cre)-based conditional gene knockout in mice, which is a common tool to show the effect of disrupted gene functions only in one period of a research animal’s life. However, other types of such antibiotics have been shown to have...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-08-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Synergistic Cytotoxicity Effect by Combination Treatment of Polyketide Derivatives from Annona muricata Linn Leaves and Doxorubicin as Potential Anticancer Material on Raji Cell Line

    Science.gov (United States)

    Artanti, A. N.; Astirin, O. P.; Prayito, A.; Fisma, R.; Prihapsara, F.

    2018-03-01

    Nasopharynx cancer is one of the most deadly cancer. The main priority of nasopharynx cancer treatment is the use of chemotherapeutic agents, especially doxorubicin. However, doxorubicin might also lead to diverse side effect. An approach recently develop to overcome side effect of doxorubicin is to used of combined chemotherapeutic agent. One of the compounds found effication as an anticancer agent on nasopharynx cancer is acetogenin, a polyketide compound that is abundant in Annona muricata L. leaves. This study has been done to examine polyketide derivatives was isolated from Annona muricata L. which has potency to induce apoptosis by p53 expression on raji cell line. The determination of cytotoxic combination activity from polyketide derivative and doxorubicin was evaluated using MTT assay to obtain the value of CI (combination index). Data analysis showed that combination of polyketide derivative from Annona muricata L. (14,4 µg/ml) and doxorubicin with all of concentration performed synergistic effect on raji cell line with CI value from 0.13 – 0.65.

  13. [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.

  14. The anticancer activity of propolis

    Directory of Open Access Journals (Sweden)

    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.

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-04-03

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

  17. Anticancer effects of kaempferol in A375 human malignant melanoma cells are mediated via induction of apoptosis, cell cycle arrest, inhibition of cell migration and downregulation of m-TOR/PI3K/AKT pathway.

    Science.gov (United States)

    Yang, Jia; Xiao, Peng; Sun, Jiaming; Guo, Liang

    2018-01-01

    Melanoma is an aggressive form of human cancer with limited treatment options currently available. The present study was aimed to evaluate the anticancer activity of kaempferol (KAM) against the human malignant melanoma A375 cell line along with evaluation of its effects on apoptosis, cell cycle, cell migration and m-TOR/PI3K/AKT pathway. Effects on cell viability were assessed by MTT assay while clonogenic assay measured the effects of KAM on colony formation. Annexin V assay evaluated the apoptotic effects of KAM in these cells using flow cytometry. Effects on cell cycle were determined by using flow cytometry with propidium iodide (PI) as probe. The effects of KAM on m-TOR/ PI3K/AKT signalling pathway were evaluated by western blot assay. MTT assay indicated that KAM exhibits a significant anticancer activity against A375 cells with an IC50 of 20 μM. These antiproliferative effects of KAM were also supported by the colony formation assay wherein KAM reduced the colony formation in a dose-dependent manner. The anticancer effect of KAM was found to be due to the initiation of apoptosis in human malignant melanoma A375 cells. Additionally, KAM also exhibited the capacity to trigger G2/M cell cycle arrest and to inhibit the cell migratory potential of A375 cells. KAM caused significant downregulation of m-TOR, phosphorylated (p) m-TOR, PI3K, p-PI3K and Akt protein levels in A375 malignantmelanoma cells. KAM exerts potent anticancer effects via induction of apoptosis, G2/M cell cycle arrest, cell migration inhibition and downregulation of m-TOR, pm-TOR, PI3K, p-PI3K and Akt protein levels.

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

    Directory of Open Access Journals (Sweden)

    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

  19. An Atomic Force Microscope Study Revealed Two Mechanisms in the Effect of Anticancer Drugs on Rate-Dependent Young's Modulus of Human Prostate Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Juan Ren

    Full Text Available Mechanical properties of cells have been recognized as a biomarker for cellular cytoskeletal organization. As chemical treatments lead to cell cytoskeletal rearrangements, thereby, modifications of cellular mechanical properties, investigating cellular mechanical property variations provides insightful knowledge to effects of chemical treatments on cancer cells. In this study, the effects of eight different anticancer drugs on the mechanical properties of human prostate cancer cell (PC-3 are investigated using a recently developed control-based nanoindentation measurement (CNM protocol on atomic force microscope (AFM. The CNM protocol overcomes the limits of other existing methods to in-liquid nanoindentation measurement of live cells on AFM, particularly for measuring mechanical properties of live cells. The Young's modulus of PC-3 cells treated by the eight drugs was measured by varying force loading rates over three orders of magnitude, and compared to the values of the control. The results showed that the Young's modulus of the PC-3 cells increased substantially by the eight drugs tested, and became much more pronounced as the force load rate increased. Moreover, two distinct trends were clearly expressed, where under the treatment of Disulfiram, paclitaxel, and MK-2206, the exponent coefficient of the frequency- modulus function remained almost unchanged, while with Celebrex, BAY, Totamine, TPA, and Vaproic acid, the exponential rate was significantly increased.

  20. Combination Treatment of Polo-Like Kinase 1 and Tankyrase-1 Inhibitors Enhances Anticancer Effect in Triple-negative Breast Cancer Cells.

    Science.gov (United States)

    Ha, Geun-Hyoung; Kim, Dong-Young; Breuer, Eun-Kyoung; Kim, Chung Kwon

    2018-03-01

    Breast cancer is the most common malignant cancer type in women, and triple-negative breast cancer (TNBC) is an extremely aggressive subtype of breast cancer with poor prognosis rates. The present study investigated the antitumor effect of polo-like kinase 1 (PLK1) inhibitor in combination with the tankyrase-1 (TNKS1) inhibitor on TNBC cells. We evaluated the antitumor effects of combination therapy with PLK1 and TNKS1 inhibitor using cell viability analysis, apoptosis assay and transwell assay for cell invasion and migration in TNBC cells. Combination treatment with PLK1 and TNKS1 inhibitors not only inhibited the invasion and migration capacity of TNBC cells, but also increased the apoptosis and cell death of TNBC cells. The viability of TNBC cells with low expression of β-catenin and high expression of PLK1 was not affected by treatment with PLK1 inhibitor. However, the combination treatment with the TNKS1 inhibitor significantly decreased cell invasion and migration and increased apoptosis. Combination therapy of PLK1 and TNKS1 inhibitors may improve the therapeutic efficacy of the current treatment for TNBC. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  1. 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...... lines (BT4C, BT4Cn, U87MG, N2a, PC12-E2, CSML0, CSML100, HeLa, L929, Swiss 3T3). Results: VPA induced significant histone deacetylase (HDAC) inhibition in most of the cell lines, but the degree of inhibition was highly cell type-specific. Moreover, cell growth, motility and the degree of Erk1....../2 phosphorylation were inhibited, activated, or unaffected by VPA in a cell type-specific manner. Importantly, no relationship was found between the effects of VPA on HDAC inhibition and changes in the degree of Erk1/2 phosphorylation, cell growth, or motility. In contrast, VPA-induced modulation of the MAPK...

  2. 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

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

    Science.gov (United States)

    Darbani, Behrooz; Noeparvar, Shahin; Borg, Søren

    2015-01-01

    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 the treatments

  4. Transcript level characterization of a cDNA encoding stress regulated NAC transcription factor in the mangrove plant Avicennia marina.

    Science.gov (United States)

    Ganesan, G; Sankararamasubramanian, H M; Narayanan, Jithesh M; Sivaprakash, K R; Parida, Ajay

    2008-10-01

    NAC transcription factors are a family of functionally diverse proteins responsive to biotic and abiotic stresses. A full-length cDNA isolated from the salt stressed mangrove plant Avicennia marina showed high sequence identity to NAC proteins induced upon biotic stress in tomato and potato. The predicted protein sequence had all the highly conserved sub domains characteristic of NAC domain containing proteins. Northern analysis for AmNAC1 expression under tolerable (250 mM) concentration of NaCl revealed up regulation of the transcript after 48 h and higher transcript level after 10 days of treatment. Induction of AmNAC1 after 12h of ABA treatment was similar to the treatment with stressful (500 mM) concentration of NaCl. The results suggest the involvement of AmNAC1 in early salt stress response and long-term adjustment to salt, besides a role for ABA in its expression under salt stress conditions.

  5. DYRK1A Controls HIV-1 Replication at a Transcriptional Level in an NFAT Dependent Manner.

    Directory of Open Access Journals (Sweden)

    Thijs Booiman

    Full Text Available Transcription of the HIV-1 provirus is regulated by both viral and host proteins and is very important in the context of viral latency. In latently infected cells, viral gene expression is inhibited as a result of the sequestration of host transcription factors and epigenetic modifications.In our present study we analyzed the effect of host factor dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A on HIV-1 replication. We show that DYRK1A controls HIV-1 replication by regulating provirus transcription. Downregulation or inhibition of DYRK1A increased LTR-driven transcription and viral replication in cell lines and primary PBMC. Furthermore, inhibition of DYRK1A resulted in reactivation of latent HIV-1 provirus to a similar extent as two commonly used broad-spectrum HDAC inhibitors. We observed that DYRK1A regulates HIV-1 transcription via the Nuclear Factor of Activated T-cells (NFAT by promoting its translocation from the nucleus to the cytoplasm. Therefore, inhibition of DYRK1A results in increased nuclear levels of NFAT and increased NFAT binding to the viral LTR and thus increasing viral transcription.Our data indicate that host factor DYRK1A plays a role in the regulation of viral transcription and latency. Therefore, DYRK1A might be an attractive candidate for therapeutic strategies targeting the viral reservoir.

  6. 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.

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

    Science.gov (United States)

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

    2016-04-01

    Much interest has been piqued regarding the quality of one's environment at early ages in modulating the susceptibility to drug addiction in adulthood. However, the molecular mechanisms that are engaged during early trauma and mediate the risk for drug addiction are poorly understood. In rodents, exposure to early-life stress alters the rewarding effects of cocaine, amphetamine, and morphine in adulthood. Recently, we demonstrated that the exposure of juvenile mice to social threat (Social Stress, S-S) promoted cocaine-seeking behavior and relapse of cocaine-seeking after periods of withdrawal, compared with unhandled controls (UN) and with juvenile mice that experienced only daily isolation in a novel environment (no social stress, NS-S). Interestingly, while the exposure to NS-S slightly increased cocaine-seeking behavior compared with UN, the same was not sufficient to promote cocaine reinstatement. In this study, we examined the long-term transcriptional changes that are induced by S-S compared to NS-S and linked the increased susceptibility of S-S mice to cocaine reinstatement. To this end, we performed genome-wide RNA sequencing analysis in the nucleus accumbens (NAC), which revealed that 89 transcripts were differentially expressed between S-S and NS-S mice. By Gene Ontology classification, these hits were enriched in genes that mediate cell proliferation, neuronal differentiation, and neuron/forebrain development. Eleven of these genes have been reported to be involved in substance use disorders, and the remaining genes are novel candidates in this area. We characterized 4 candidates with regard to their significant neurobiological relevance (ZIC1, ZIC2, FABP7, and PRDM12) and measured their expression in the NAC by immunohistochemistry. These findings provide insights into novel molecular mechanisms in NAC that might be associated with the risk of relapse in cocaine-dependent individuals. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2010-01-15

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

  9. Mutation of Gly717Phe in human topoisomerase 1B has an effect on enzymatic function, reactivity to the camptothecin anticancer drug and on the linker domain orientation.

    Science.gov (United States)

    Wang, Zhenxing; D'Annessa, Ilda; Tesauro, Cinzia; Croce, Stefano; Ottaviani, Alessio; Fiorani, Paola; Desideri, Alessandro

    2015-08-01

    Human topoisomerase 1B controls the topological state of supercoiled DNA allowing the progression of fundamental cellular processes. The enzyme, which is the unique molecular target of the natural anticancer compound camptothecin, acts by cleaving one DNA strand and forming a transient protein-DNA covalent adduct. In this work the role of the Gly717 residue, located in a α-helix structure bridging the active site and the linker domain, has been investigated mutating it in Phe. The mutation gives rise to drug resistance in vivo as observed through a viability assay of yeast cells. In vitro activity assays show that the mutant is characterized by a fast religation rate, only partially reduced by the presence of the drug. Comparative molecular dynamics simulations of the native and mutant proteins indicate that the mutation of Gly717 affects the motion orientation of the linker domain, changing its interaction with the DNA substrate, likely affecting the strand rotation and religation rate. The mutation also causes a slight rearrangement of the active site and of the drug binding site, providing an additional explanation for the lowered effect of camptothecin toward the mutant. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Synthesis and biological evaluation of isomeric methoxy substitutions on anti-cancer indolyl-pyridinyl-propenones: Effects on potency and mode of activity.

    Science.gov (United States)

    Trabbic, Christopher J; George, Sage M; Alexander, Evan M; Du, Shengnan; Offenbacher, Jennifer M; Crissman, Emily J; Overmeyer, Jean H; Maltese, William A; Erhardt, Paul W

    2016-10-21

    Certain indolyl-pyridinyl-propenone analogues kill glioblastoma cells that have become resistant to conventional therapeutic drugs. Some of these analogues induce a novel form of non-apoptotic cell death called methuosis, while others primarily cause microtubule disruption. Ready access to 5-indole substitution has allowed characterization of this position to be important for both types of mechanisms when a simple methoxy group is present. We now report the syntheses and biological effects of isomeric methoxy substitutions on the indole ring. Additionally, analogues containing a trimethoxyphenyl group in place of the pyridinyl moiety were evaluated for anticancer activity. The results demonstrate that the location of the methoxy group can alter both the potency and the mechanism of cell death. Remarkably, changing the methoxy from the 5-position to the 6-position switched the biological activity from induction of methuosis to disruption of microtubules. The latter may represent a prototype for a new class of mitotic inhibitors with potential therapeutic utility. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  11. TGI-Simulator: a visual tool to support the preclinical phase of the drug discovery process by assessing in silico the effect of an anticancer drug.

    Science.gov (United States)

    Terranova, Nadia; Magni, Paolo

    2012-02-01

    This paper presents TGI-Simulator, a software tool designed to show, through a 2-D graphical animation, the simulated time effect of an anticancer drug on a tumor mass by exploiting the well-known Tumor Growth Inhibition (TGI) model published by Simeoni et al. [1]. Simeoni TGI model is a mathematical model routinely used by pharma companies and researchers during the drug development process. The application is based on a Java graphical user interface (GUI) including a self installing differential equation solver implemented in Matlab together with an optimization algorithm that performs model identification via Weighted Least Squares (WLS). However, it can graphically show also the simulation results obtained within other scientific software tools, if they are preventively stored into a suitable ASCII file. The tool would be a valid support also for researchers with no specific skills in scientific calculations and in pharmacokinetic and pharmacodynamic modeling but daily involved in pharma companies drug development processes at different levels. The availability of a movie with a temporal varying 2-D iconographic representation is an original instrument to communicate results and learn Simeoni TGI model and its potential application in preclinical studies. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  12. Comparative effect of two pan-class I PI3K inhibitors used as anticancer drugs on human T cell function.

    Science.gov (United States)

    Blanco, Belén; Herrero-Sánchez, Carmen; Rodríguez-Serrano, Concepción; Sánchez-Barba, Mercedes; Del Cañizo, María Consuelo

    2015-09-01

    The phosphatidylinositol 3-kinase (PI3K) pathway is commonly deregulated in cancer and, thus, PI3K has been recognized as an attractive molecular target for novel anti-cancer therapies. However, the effect of PI3K inhibitors on T-cell function, a key component of antitumor immunity, has been scantly explored. The objective of this study was to investigate the effect on human T-cell activation of two PI3K inhibitors currently being tested in clinical trials: PX-866 and BKM120. Their activity against a leukemic T cell line was also assessed. For that purpose, Jurkat cells or anti-CD3/anti-CD28 stimulated human peripheral blood mononuclear cells were cultured in the presence of different concentrations of PX-866 or BKM120 and their effect on T-cell proliferation, apoptosis, expression of activation markers and cytokine secretion was analyzed by flow cytometry. In addition, Akt and Erk phosphorylation was analyzed by Western blotting. Both PX-866 and BKM120 decreased viability of Jurkat cells and blocked cell cycle progression. Regarding primary T cells, both compounds similarly inhibited expression of activation markers and cytokine secretion, although they did not induce apoptosis of stimulated T cells. Interestingly, we found differences in their ability to block T-cell proliferation and IL-2 secretion, exerting BKM120 a more potent inhibition. These disparate effects could be related to differences observed in PI3K/Akt and RAS/MEK/ERK signaling between PX-866 and BKM120 treated cells. Our results suggest that, when selecting a PI3K inhibitor for cancer therapy, immunosuppressive characteristics should be taken into account in order to minimize detrimental effects on immune function. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    NARCIS (Netherlands)

    Fliedner, S.M.; Engel, T.G.P.; Lendvai, N.K.; Shankavaram, U.; Nolting, S.; Wesley, R.; Elkahloun, A.G.; Ungefroren, H.; Oldoerp, A.; Lampert, G.; Lehnert, H.; Timmers, H.J.; Pacak, K.

    2014-01-01

    To date, malignant pheochromocytomas and paragangliomas (PHEOs/PGLs) cannot be effectively cured and thus novel treatment strategies are urgently needed. Lovastatin has been shown to effectively induce apoptosis in mouse PHEO cells (MPC) and the more aggressive mouse tumor tissue-derived cells

  14. Inhibition of microRNA-500 has anti-cancer effect through its conditional downstream target of TFPI in human prostate cancer.

    Science.gov (United States)

    Cai, Bing; Chen, Wei; Pan, Yue; Chen, Hongde; Zhang, Yirong; Weng, Zhiliang; Li, Yeping

    2017-07-01

    We investigated the prognostic potential and regulatory mechanism of microRNA-500 (miR-500), and human gene of tissue factor pathway inhibitor (TFPI) in prostate cancer. MiR-500 expression was assessed by qRT-PCR in prostate cancer cell lines and primary tumors. Cancer patients' clinicopathological factors and overall survival were analyzed according to endogenous miR-500 level. MiR-500 was downregulated in DU145 and VCaP cells. Its effect on prostate cancer proliferation, invasion in vitro, and tumorigenicity in vivo, were probed. Possible downstream target of miR-500, TFPI was assessed by luciferase assay and qRT-PCR in prostate cancer cells. In miR-500-downregulated DU145 and VCaP cells, TFPI was silenced to see whether it was directly involved in the regulation of miR-500 in prostate cancer. TFPI alone was either upregulated or downregulated in DU145 and VCaP cells. Their effect on prostate cancer development was further evaluated. MiR-500 is upregulated in both prostate cancer cells and primary tumors. In prostate cancer patients, high miR-500 expression is associated with poor prognosis and overall survival. In DU145 and VCaP cells, miR-500 downregulation inhibited cancer proliferation, invasion in vitro, and explant growth in vivo. TFPI was verified to be associated with miR-500 in prostate cancer. Downregulation of TFPI reversed anti-cancer effects of miR-500 downregulation in prostate cancer cells. However, neither TFPI upregulation nor downregulation alone had any functional impact on prostate cancer development. MiR-500 may be a potential biomarker and molecular target in prostate cancer. TFPI may conditionally regulate prostate cancer in miR-500-downregualted prostate cancer cells. © 2017 Wiley Periodicals, Inc.

  15. Cold-induced changes in stress hormone and steroidogenic transcript levels in cunner (Tautogolabrus adspersus), a fish capable of metabolic depression.

    Science.gov (United States)

    Alzaid, Abdullah; Hori, Tiago S; Hall, Jennifer R; Rise, Matthew L; Gamperl, A Kurt

    2015-12-01

    The cunner (Tautogolabrus adspersus) is a fish with a wide latitudinal distribution that is capable of going into metabolic depression during the winter months, and thus, represents a unique model to investigate the impacts of cold temperatures on the stress response. In this study, we measured resting (pre-stress) plasma cortisol levels in 10 °C and 0 °C acclimated cunner from Newfoundland, and both catecholamine and cortisol levels after they were given a standardized handling stress (i.e. 1 min air exposure). In addition, we cloned and characterized cDNAs for several key genes of the cortisol-axis [cytochrome P450scc, steroidogenic acute regulatory protein (StAR) and a glucocorticoid receptor (GR) most likely to be an ortholog of the teleost GR2], determined the tissue distribution of their transcripts, and measured their constitutive (i.e. pre-stress) transcript levels in individuals acclimated to both temperatures. In cunner acclimated to 0 °C, post-stress epinephrine and norepinephrine levels were much lower (by approximately 9- and 5-fold, respectively) compared to 10 °C acclimated fish, and these fish had relatively low resting cortisol levels (~15 ngml(-1)) and showed a typical post-stress response. In contrast, those acclimated to 10 °C had quite high resting cortisol levels (~75 ngml(-1)) that actually decreased (to ~20 ngml(-1)) post-stress before returning to pre-stress levels. Finally, fish acclimated to 10 °C had higher P450scc transcript levels in the head kidney and lower levels of GR transcript in both the head kidney and liver. Taken together, these results suggest that: (1) temperature has a profound effect on the stress response of this species; and (2) although the ancestors of this species inhabited warm waters (i.e. they are members of the family Labridae), populations of cunner from colder regions may show signs of stress at temperatures as low as 10 °C. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Protective effect of ginsenoside Rh3 against anticancer drug-induced apoptosis in LLC-PK1 kidney cells

    Directory of Open Access Journals (Sweden)

    Hye Lim Lee

    2017-04-01

    Conclusion: These results demonstrate that inhibition of the JNK and ERK mitogen-activated protein kinase signaling cascade plays a critical role in mediating the renoprotective effect of ginsenoside Rh3.

  17. Oral delivery of anticancer drugs

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  18. Abiotic stress-induced oscillations in steady-state transcript levels of Group 3 LEA protein genes in the moss, Physcomitrella patens.

    Science.gov (United States)

    Shinde, Suhas; Shinde, Rupali; Downey, Frances; Ng, Carl K-Y

    2013-01-01

    The moss, Physcomitrella patens is a non-seed land plant belonging to early diverging lineages of land plants following colonization of land in the Ordovician period in Earth's history. Evidence suggests that mosses can be highly tolerant of abiotic stress. We showed previously that dehydration stress and abscisic acid treatments induced oscillations in steady-state levels of LEA (Late Embryogenesis Abundant) protein transcripts, and that removal of ABA resulted in rapid attenuation of oscillatory increases in transcript levels. Here, we show that other abiotic stresses like salt and osmotic stresses also induced oscillations in steady-state transcript levels and that the amplitudes of the oscillatory increases in steady-state transcript levels are reflective of the severity of the abiotic stress treatment. Together, our results suggest that oscillatory increases in transcript levels in response to abiotic stresses may be a general phenomenon in P. patens and that temporally dynamic increases in steady-state transcript levels may be important for adaptation to life in constantly fluctuating environmental conditions.

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

    International Nuclear Information System (INIS)

    Jo, Miran; Park, Mi Hee; Kollipara, Pushpa Saranya; An, Byeong Jun; Song, Ho Sueb; Han, Sang Bae; Kim, Jang Heub; Song, Min Jong; Hong, Jin Tae

    2012-01-01

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

  20. The potentized homeopathic drug, Lycopodium clavatum (5C and 15C) has anti-cancer effect on hela cells in vitro.

    Science.gov (United States)

    Samadder, Asmita; Das, Sreemanti; Das, Jayeeta; Paul, Avijit; Boujedaini, Naoual; Khuda-Bukhsh, Anisur Rahman

    2013-08-01

    Cancer is a disease that needs a multi-faceted approach from different systems of medicine. The purpose of this study was to evaluate whether homeopathically-potentized ultra-high dilutions of Lycopodium Clavatum (LC-5C and LC-15C, respectively) have any anti-cancer effects on HeLa cells. Cells were exposed to either LC-5C (diluted below Avogadro's limit, i.e., 10(-10)) or LC-15C (diluted beyond Avogadro's limit, i.e., 10(-30)) (drug-treated) or to 30% succussed ethanol ("vehicle" of the drug). The drug-induced modulation in the percent cell viability, the onset of apoptosis, and changes in the expressions of Bax, Bcl2, caspase 3, and Apaf proteins in inter-nucleosomal DNA, in mitochondrial membrane potentials and in the release of cytochrome-c were analyzed by utilizing different experimental protocols. Results revealed that administration of LC-5C and LC-15C had little or no cytotoxic effect in normal peripheral blood mononuclear cells, but caused considerable cell death through apoptosis in cancer (HeLa) cells, which was evident from the induction of DNA fragmentation, the increases in the expressions of protein and mRNA of caspase 3 and Bax, and the decreases in the expressions of Bcl2 and Apaf and in the release of cytochrome-c. Thus, the highly-diluted, dynamized homeopathic remedies LC-5C and LC-15C demonstrated their capabilities to induce apoptosis in cancer cells, signifying their possible use as supportive medicines in cancer therapy. Copyright © 2013. Published by Elsevier B.V.

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

    Science.gov (United States)

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

    2016-01-01

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

  2. Production and evaluation of cytotoxic effects of DT386-BR2 fusion protein as a novel anti-cancer agent.

    Science.gov (United States)

    Shafiee, Fatemeh; Rabbani, Mohammad; Jahanian-Najafabadi, Ali

    2016-11-01

    The aim of this study was to produce a fusion protein consisting of the catalytic and translocation domains of diphtheria toxin fused to BR2, a cancer specific cell penetrating peptide, and evaluation of its cytotoxic effects for targeted eradication of cancer cells. For this purpose, The DT386-BR2 structure was predicted using Modeller 9.14 and the best predicted model was selected based on the minimum DOPE score. A synthetic gene encoding DT386-BR2 was cloned in pET28a expression vector, expressed and purified by affinity chromatography. SDS-PAGE and Western blotting confirmed the expression of the DT386-BR2 fusion protein by revealing a band of about 47kDa after the induction of the expression. Finally, the purified protein was subjected to MTT assay for evaluation of its cyto-lethal effects on cancer and normal cell lines. Statistical analysis showed significant reduction in survival percent of HeLa and MCF-7 cancer cells in comparison to negative control (PBS), while the cytotoxic effect was not significant on the normal cells, i.e. HUVEC and HEK 293. The IC50 of DT386-BR2 for HeLa and MCF-7 was about 0.55 and 2.08μg/ml, respectively. In conclusion, the production and purification of DT386-BR2 fusion protein was successfully achieved and its cytotoxic effects on the studied cancer cell lines was established. The promising cytotoxic effects of this newly constructed fusion protein made it a suitable candidate for targeted therapy of cancer, and further in vitro and in vivo studies on this fusion protein is underway. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Andreia A. Borges

    2011-01-01

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

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

    OpenAIRE

    Choi, Kiheon; Lim, Hyun Kyung; Oh, Sung Ryong; Chung, Woo-Hyun; Jung, Joohee

    2017-01-01

    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...

  5. In vitro anticancer effect of venom from Cuban scorpion Rhopalurus junceus against a panel of human cancer cell lines.

    Science.gov (United States)

    Díaz-García, Alexis; Morier-Díaz, Luis; Frión-Herrera, Yahima; Rodríguez-Sánchez, Hermis; Caballero-Lorenzo, Yamira; Mendoza-Llanes, Dianeya; Riquenes-Garlobo, Yanelis; Fraga-Castro, José A

    2013-01-01

    In Cuba the endemic species of scorpion Rhopalurus junceus has been used in traditional medicine for cancer treatment. However, there is little scientific evidence about its potential in cancer therapy. The effect of a range of scorpion venom concentrations (0.1, 0.25, 0.5, 0.75 and 1mg/ml) against a panel of human tumor cell lines from epithelial (Hela, SiHa, Hep-2, NCI-H292, A549, MDA-MB-231, MDA-MB-468, HT-29), hematopoietic origins (U937, K562, Raji) and normal cells (MRC-5, MDCK, Vero) was determined by the MTT assay. Additionally, the effect of venom on tumor cell death was assayed by Fluorescence microscopy, RT-PCR and western blot. Only the epithelial cancer cells showed significant cell viability reduction, with medium cytotoxic concentration (IC50) ranging from 0.6-1mg/ml, in a concentration-dependent manner. There was no effect on either normal or hematopoietic tumor cells. Scorpion venom demonstrated to induce apoptosis in less sensitive tumor cells (Hela) as evidenced by chromatin condensation, over expression of p53 and bax mRNA, down expression of bcl-2 mRNA and increase of activated caspases 3, 8, 9. In most sensitive tumor cells (A549), scorpion venom induced necrosis evidenced by acridine orange/ethidium bromide fluorescent dyes and down-expression of apoptosis-related genes. We concluded the scorpion venom from R. junceus possessed a selective and differential toxicity against epithelial cancer cells. This is the first report related to biological effect of R. junceus venom against a panel of tumor cells lines. All these results make R. junceus venom as a promise natural product for cancer treatment.

  6. Anti-cancer effect of Annona Muricata Linn Leaves Crude Extract (AMCE) on breast cancer cell line

    OpenAIRE

    Syed Najmuddin, Syed Umar Faruq; Romli, Muhammad Firdaus; Hamid, Muhajir; Alitheen, Noorjahan Banu; Nik Abd Rahman, Nik Mohd Afizan

    2016-01-01

    Background Annona muricata Linn which comes from Annonaceae family possesses many therapeutic benefits as reported in previous studies and to no surprise, it has been used in many cultures to treat various ailments including headaches, insomnia, and rheumatism to even treating cancer. However, Annona muricata Linn obtained from different cultivation area does not necessarily offer the same therapeutic effects towards breast cancer (in regards to its bioactive compound production). In this stu...

  7. Development of a chimeric recombinant disintegrin as a cost-effective anticancer agent with promising translational potential

    Science.gov (United States)

    Minea, Radu; Helchowski, Corey; Rubino, Barbara; Brodmann, Kyle; Swenson, Stephen; Markland, Francis

    2011-01-01

    Vicrostatin (VCN) is a chimeric recombinant disintegrin generated in Origami B (DE3) E. coli as a genetic fusion between the C-terminal tail of a viperid disintegrin echistatin and crotalid disintegrin contortrostatin (CN). The therapeutic modulation of multiple integrin pathways via soluble disintegrins was previously shown by us and others to elicit potent anti-angiogenic and anti-metastatic effects in several animal cancer models. Despite these favorable attributes, these polypeptides are notoriously difficult to produce recombinantly in significant quantity due to their structure which requires the correct pairing of multiple disulfide bonds for biological activity. In this report, we show that VCN can be reliably produced in large amounts (yields in excess of 200mg of active purified disintegrin per liter of bacterial culture) in Origami B (DE3), an E. coli expression strain engineered to support the folding of disulfide-rich heterologous proteins directly in its oxidative cytoplasmic compartment. VCN retains the integrin binding specificity of both parental molecules it was derived from, but with a different binding affinity profile. While competing for the same integrin receptors that are preferentially upregulated in the tumor microenvironment, VCN exerts a potent inhibitory effect on endothelial cell (EC) migration and tube formation in a dose-dependent manner, by forcing these cells to undergo significant actin cytoskeleton reorganization when exposed to this agent in vitro. Moreover, VCN has a direct effect on breast cancer cells inhibiting their in vitro motility. In an effort to address our main goal of developing a clinically relevant delivery method for recombinant disintegrins, VCN was efficiently packaged in liposomes (LVCN) and evaluated in vivo in an animal breast cancer model. Our data demonstrate that LVCN is well tolerated, its intravenous administration inducing a significant delay in tumor growth and an increase in animal survival, results

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Mutation of Gly717Phe in human topoisomerase 1B has an effect on enzymatic function, reactivity to the camptothecin anticancer drug and on the linker domain orientation

    DEFF Research Database (Denmark)

    Wang, Zhenxing; D'Annessa, Ilda; Tesauro, Cinzia

    2015-01-01

    Human topoisomerase 1B controls the topological state of supercoiled DNA allowing the progression of fundamental cellular processes. The enzyme, which is the unique molecular target of the natural anticancer compound camptothecin, acts by cleaving one DNA strand and forming a transient protein–DN...

  10. How to modify 7-azaindole to form cytotoxic Pt(II) complexes: Highly in vitro anticancer effective cisplatin derivatives involving halogeno-substituted 7-azaindole

    Czech Academy of Sciences Publication Activity Database

    Štarha, P.; Trávníček, Z.; Popa, A.; Popa, I.; Muchová, T.; Brabec, Viktor

    2012-01-01

    Roč. 115, SI (2012), s. 57-63 ISSN 0162-0134 R&D Projects: GA ČR(CZ) GAP301/10/0598 Institutional research plan: CEZ:AV0Z50040702 Keywords : platinum * anticancer * DNA Subject RIV: BO - Biophysics Impact factor: 3.197, year: 2012

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

    Directory of Open Access Journals (Sweden)

    Hartmann J

    2011-03-01

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

  12. Expressions of p53 and PUMA in fibroblasts of systemic sclerosis patients are normal at transcription level.

    Science.gov (United States)

    Mahmoudi, Mohammad Bagher; Abed Khojasteh, Majid; Alsahebfosoul, Fereshteh; Gharibdoost, Farhad; Mostafaei, Shayan; Ganjalikhani-Hakemi, Mazdak; Mahmoudi, Mahdi

    2017-09-14

    Systemic sclerosis (SSc) fibroblasts show resistance apoptosis mechanisms, which enhances the fibrosis stage of the disease. Impaired function of p53 upregulated modulator of apoptosis (PUMA) has been related to deficits in p53-dependant apoptosis pathway. This study aimed to evaluate the transcriptional levels of p53 and PUMA mRNAs in fibroblasts from SSc patients and compare it with healthy individuals. In this case-control study, skin biopsy samples were obtained from 19 patients with diffuse cutaneous SSc (DcSSc) and 16 healthy controls. Afterward, dermal fibroblasts were isolated and cultured. After extraction of total RNA from cultured fibroblasts, complementary DNA (cDNA) was synthesized. mRNA quantification was carried out using real-time PCR, SYBR Green PCR master mix, and specific primers for p53 and PUMA. No significant alteration was observed in mRNA expression levels of p53 and PUMA (P = .99 and .23, respectively) in fibroblasts from SSc patients compared with controls. Apoptosis pathways are impaired in fibroblasts from patients with SSc, leading to chronic fibrosis. Nonetheless, PUMA/p53 pathway may not be involved in dysfunction of apoptosis mechanisms in fibroblasts of patients with SSc. © 2017 Wiley Periodicals, Inc.

  13. In vitro anticancer effect of venom from Cuban scorpion Rhopalurus junceus against a panel of human cancer cell lines

    OpenAIRE

    D?az-Garc?a, Alexis; Morier-D?az, Luis; Fri?n-Herrera, Yahima; Rodr?guez-S?nchez, Hermis; Caballero-Lorenzo, Yamira; Mendoza-Llanes, Dianeya; Riquenes-Garlobo, Yanelis; Fraga-Castro, Jos? A

    2013-01-01

    In Cuba the endemic species of scorpion Rhopalurus junceus has been used in traditional medicine for cancer treatment. However, there is little scientific evidence about its potential in cancer therapy. The effect of a range of scorpion venom concentrations (0.1, 0.25, 0.5, 0.75 and 1mg/ml) against a panel of human tumor cell lines from epithelial (Hela, SiHa, Hep-2, NCI-H292, A549, MDA-MB-231, MDA-MB-468, HT-29), hematopoietic origins (U937, K562, Raji) and normal cells (MRC-5, MDCK, Vero) w...

  14. The C8 side chain is one of the key functional group of Garcinol for its anti-cancer effects.

    Science.gov (United States)

    Zhou, Xin-Ying; Cao, Jing; Han, Chao-Ming; Li, Shu-Wen; Zhang, Chen; Du, Yin-Duan; Zhou, Qian-Qian; Zhang, Xin-Yan; Chen, Xin

    2017-04-01

    Garcinol from the fruit rind of Garcinia indica shows anti-carcinogenic and anti-inflammatory properties, but its mechanism and key functional groups were still need to be identified. Our previous computer modeling suggested that the C8 side chain of Garcinol is so large that it may influence the bioactivity of the compound. 8-Me Garcinol, a derivative of Garcinol in which the bulky side chain at the C8 position of Garcinol is replaced with a much smaller methyl group, was synthesized through a 12-step procedure starting from 1,3-cyclohexanedione. The antitumor activity of Garcinol and 8-Me Garcinol was evaluated in vitro by MTT, cell cycle and cell apoptosis assays. The results showed that 8-Me Garcinol had weaker inhibitory activity on cells proliferation, and little effects on cell cycle and apoptosis in oral cancer cell line SCC15 cells when compared with Garcinol. All of the results indicated 8-Me Garcinol exerts weaker antitumor activity than Garcinol, and the C8 side chain might be an important active site in Garcinol. Changing the C8 side chain will affect the inhibitory effect of Garcinol. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Potential Anticancer Effects of Polyphenols from Chestnut Shell Extracts: Modulation of Cell Growth, and Cytokinomic and Metabolomic Profiles

    Directory of Open Access Journals (Sweden)

    Angela Sorice

    2016-10-01

    Full Text Available In this study, a hydroalcoholic chestnut shell extract was characterized and tested on six different human cell lines. Gallic, ellagic, and syringic acids were the most abundant non-condensed compounds in the chestnut extract, as determined by high performance liquid chromatography (HPLC. Tannins were mainly represented by condensed monomeric units of epigallocatechin and catechin/epicatechin. After 48 h of treatment, only the human hepatoblastoma HepG2 cells reached an inhibition corresponding to IC50 with an increase of apoptosis and mitochondrial depolarization. The cytokinome evaluation before and after treatment revealed that the vascular endothelial growth factor (VEGF and the tumor necrosis factor (TNF-α decreased after the treatment, suggesting a potential anti-angiogenic and anti-inflammatory effect of this extract. Moreover, the metabolome evaluation by 1H-NMR evidenced that the polyphenols extracted from chestnut shell (PECS treatment affected the levels of some amino acids and other metabolites. Overall, these data highlight the effects of biomolecules on cell proliferation, apoptosis, cell cycle and mitochondrial depolarization, and on cytokinomics and metabolomics profiles.

  16. Improving antiproliferative effect of the anticancer drug cytarabine on human promyelocytic leukemia cells by coating on Fe3O4@SiO2 nanoparticles.

    Science.gov (United States)

    Shahabadi, Nahid; Falsafi, Monireh; Mansouri, Kamran

    2016-05-01

    In this study, Fe3O4@SiO2-cytarabine magnetic nanoparticles (MNPs) were prepared via chemical coprecipitation reaction and coating silica on the surface of Fe3O4 MNPs by Stöber method via sol-gel process. The surface of Fe3O4@SiO2 MNPs was modified by an anticancer drug, cytarabine. The structural properties of the samples were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Zetasizer analyzer, and transmission electron microscopy (TEM). The results indicated that the crystalline phase of iron oxide NPs was magnetite (Fe3O4) and the average sizes of Fe3O4@SiO2-cytarabine MNPs were about 23 nm. Also, the surface characterization of Fe3O4@SiO2-cytarabine MNPs by FT-IR showed that successful coating of Fe3O4 NPs with SiO2 and binding of cytarabine drug onto the surface of Fe3O4@SiO2 MNPs were through the hydroxyl groups of the drug. The in vitro cytotoxic activity of Fe3O4@SiO2-cytarabine MNPs was investigated against cancer cell line (HL60) in comparison with cytarabine using MTT colorimetric assay. The obtained results showed that the effect of Fe3O4@SiO2-cytarabine magnetic nanoparticles on the cell lines were about two orders of magnitude higher than that of cytarabine. Furthermore, in vitro DNA binding studies were investigated by UV-vis, circular dichroism, and fluorescence spectroscopy. The results for DNA binding illustrated that DNA aggregated on Fe3O4@SiO2-cytarabine MNPs via groove binding. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Elisa Robles-Escajeda

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

  18. Synergistic antiproliferative effect of cis-diammine-dichloroplatinum (II) and a new anticancer agent, plasmanyl-(N-acyl)-ethanolamine, an inhibitor of protein kinase C.

    Science.gov (United States)

    Mikhaevich, I S; Vlasenkova, N K; Gerasimova, G K

    1991-01-01

    The action of a new anticancer agent, the semisynthetic alkyl-phospholipid plasmanyl-(N-acyl)-ethanolamine (sPNAE), namely 1-O-octadecyl-2-oleoyl-sn-glycero-3-phospho-(N-palmitoyl)-ethanolamine, on protein kinase C (PKC) was investigated, and it was found to inhibit in a dose-dependent manner PKC isolated from mouse brain. The inhibition was competitive with respect to phosphatidylserine (K(i) = 20 microM). Lyso-PNAE, a possible cell metabolite of sPNAE, also inhibited PKC. A two-site model was used to calculate the binding affinity and the number of binding sites for phorbol ester in a culture of human melanoma BRO cells. The values of Kd, the dissociation constant, were K'd = 0.5 nM and K"d = 72 nM, whereas the values of Bmax, the number of binding sites, were B'max = 4.6 x 10(4) sites cell-1, and B"max = 2.9 x 10(5) sites cell-1. sPNAE was able to reduce the affinity of BRO cells for phorbol ester with almost no changes in the number of binding sites: K'd = 1.6 nM, K"d = 557 nM, and B'max = 4 x 10(4), B"max = 1.9 x 10(5). These data suggest that sPNAE may inhibit PKC in intact cells. Since various inhibitors of PKC may enhance the antiproliferative activity of cis-diamminedichloroplatinum(II) (cis-DDP), we investigated the effect of the combination of sPNAE and cis-DDP on the proliferation of BRO cells. sPNAE synergistically enhanced the antiproliferative activity of cis-DDP.

  19. [Effect of Erlotinib in 2nd and 3rd Line Anticancer Treatment in Patients with Squamous Cell Lung Cancer - Case Series].

    Science.gov (United States)

    Šatánková, M; Brat, K; Tomíšková, M; Robešová, B; Skřičková, J

    Squamous cell carcinoma of the lung (SCC) represents cca 30-40% of new cases of non-small cell lung cancer (NSCLC) in the Czech Republic. The tyrosine kinase inhibitor erlotinib is indicated as a 1st line treatment for patients with locally advanced and metastatic disease and activating mutations in endothelial growth factor receptor (EGFR), or as a 2nd or 3rd line treatment in EGFR-negative NSCLC patients after chemotherapeutic failure. We present three case reports of patients with SCC treated with erlotinib as a 2nd or 3rd line of treatment. All patients were verified by histological analysis of tumor samples. EGFR mutation status was negative in one patient, while the other samples were not suitable for genetic screening. The therapeutic response to erlotinib lasted for 68, 40, and 13 months, resp. The patient with the longest therapeutic response (patient no. 1) is still continuing erlotinib treatment (as of December 2016). The overall survival of the two patients who died was 50 and 43 months, resp. One patient died of an unknown cause with no signs of progression of the disease on CT scans. The other patient died of terminal progression of the oncological disease. All three patients experienced major therapeutic benefit from erlotinib treatment as shown by the long periods of progression-free survival and prolonged overall survival. The three case reports demonstrate that erlotinib may be effective as a 2nd or 3rd line treatment in patients with SCC, especially in patients with limited alternative anticancer treatment options.Key words: non-small cell lung cancer - squamous cell carcinoma - erlotinib - treatment - tyrosine kinase inhibitor The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 5. 8. 2016Accepted: 14. 12. 2016.

  20. Acute aquatic toxicity assessment of six anti-cancer drugs and one metabolite using biotest battery - Biological effects and stability under test conditions.

    Science.gov (United States)

    Białk-Bielińska, Anna; Mulkiewicz, Ewa; Stokowski, Marcin; Stolte, Stefan; Stepnowski, Piotr

    2017-12-01

    Available ecotoxicological data for anti-cancer drugs and their metabolites are incomplete, and only some studies have been accompanied by chemical analysis. Therefore, the main aim of this study was to evaluate the acute toxicity of the six most commonly used cytostatics, namely cyclophosphamide (CF), ifosfamide (IF), 5-fluorouracil (5-FU), imatinib (IMT), tamoxifen (TAM) and methotrexate (MET) and its metabolite - 7-hydroxymethotrexate (7-OH-MET), towards selected aquatic organisms, namely bacteria Vibrio fischeri, algae Raphidocelis subcapitata, crustaceans Daphnia magna and duckweed Lemna minor. All ecotoxicological tests were accompanied by chemical analysis to determine the differences between nominal and actual concentrations of investigated compounds and their stability under test conditions. For unstable compounds, tests were performed in static and semi-static conditions. It was observed that L. minor was the most sensitive organism. The compounds that were most toxic to aquatic organisms were 5-FU (highly toxic to algae, EC 50  = 0.075 mg L -1 ), MET and TAM (very toxic to highly toxic to duckweed depending on the test conditions; EC 50MET 0.08-0.16 mg L -1 , EC 50TAM 0.18-0.23 mg L -1 ). It is suspected that MET and 5-FU mainly affected algae and plants most probably because the exposure time was long enough for them to cause a specific effect (they inhibit DNA replication and act predominantly on actively dividing cells). Furthermore, the obtained results also suggest that the toxicity of the metabolites/potentially produced degradation products of MET towards duckweed is lower than that of the parent form, whereas the toxicity of TAM degradation products is in the same range as that of TAM. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    International Nuclear Information System (INIS)

    Yasui, Hironobu; Inanami, Osamu; Asanuma, Taketoshi; Iizuka, Daisuke; Nakajima, Takayuki; Kon, Yasuhiro; Matsuda, Akira; Kuwabara, Mikinori

    2007-01-01

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

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

    Science.gov (United States)

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

    2015-07-01

    Although imatinib mesylate (IM) in the treatment of chronic myelogenous leukemia (CML) remains the best example of successful targeted therapy, majority of patients with CML suffer its toxicity profile and develop chemoresistance to existing therapeutic agents. Thus, there is a need to develop novel alternative therapies for the treatment of CML. Here, we investigated whether Korean red ginseng extract (KRGE) could suppress the proliferation and induce chemosensitization in human CML cells. Also, we used a human phospho-antibody array containing 46 antibodies against signaling molecules to examine a subset of phosphorylation events after treatment. Korean red ginseng extract broadly suppressed the proliferation of five different cell lines, but KRGE was found to be the most potent inducer of apoptosis against KBM-5 cells. It also abrogated the expression of Bcl-2 (B-cell lymphoma 2), Bcl-xL (B-cell lymphoma-extra large), survivin, inhibitors of apoptosis protein 1/2, COX-2 (Cyclooxygenase-2), cyclin D1, matrix metalloproteinase-9, and VEGF (Vascular endothelial growth factor), as well as upregulated the expression of pro-apoptotic gene products. Interestingly, KRGE also enhanced the cytotoxic and apoptotic effect of IM in KBM-5 cells. The combination treatment of KRGE and IM caused pronounced suppression of p38 and signal transducer and activator of transcription 5 phosphorylation and induced phosphorylation of p53 compared with the individual treatment. Our results demonstrate that KRGE can enhance the anticancer activity of IM and may have a substantial potential in the treatment of CML. Copyright © 2015 John Wiley & Sons, Ltd.

  3. Anticancer Activity of Papaver Somniferum

    Directory of Open Access Journals (Sweden)

    Döne Aslı Güler

    2016-08-01

    Full Text Available This work describes the pharmacological activity of extracts of Papaver somniferum, a poppy species. P. somniferum products are still considered as a unique source of drug for many diseases. The present study was designed to determine antiproliferative and cytotoxic effects of P. somniferum extracts on HeLa (Human Cervix Carcinoma, HT29 (Human Colorectal Adenocarcinoma, C6 (Rat Brain Tumor Cells, and Vero (African Green Monkey Kidney cell lines. Alkaloids-rich extracts of P. somniferum exhibited antiproliferative effects on various cancer cell lines, especially at high concentrations. We assessed the ability of extracts of P. somniferum to harm the membrane of the cells. Results indicated that P. somniferum extracts destroy cellular membrane in tumor cell lines at high concentrations. Remarkably, the LDH test results disclosed that cytotoxicity of P. somniferum on cells was low at mid concentrations. This may indicate its cytostatic potential. The results of this study support the efficacy of P. somniferum extracts as an anticancer agent.

  4. Oncolytic viruses as anticancer vaccines

    Directory of Open Access Journals (Sweden)

    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.

  5. 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. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Anticancer Efficacy of Polyphenols and Their Combinations

    Directory of Open Access Journals (Sweden)

    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

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

    DEFF Research Database (Denmark)

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

    2003-01-01

    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....../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...... oxidation biomarkers in the blood as well as hepatic quinone reductase activity, and that quercetin may not be the major active principle. The observation that natural carbohydrates are capable of mediating oxidative stress in vivo warrants further studies due to the central role refined and unrefined...

  8. Cationic lipid-based nanoparticles mediate functional delivery of acetate to tumor cells in vivo leading to significant anticancer effects

    Directory of Open Access Journals (Sweden)

    Brody LP

    2017-09-01

    Full Text Available Leigh P Brody,1,* Meliz Sahuri-Arisoylu,1,* James R Parkinson,1 Harry G Parkes,2 Po Wah So,3 Nabil Hajji,4 E Louise Thomas,1 Gary S Frost,5 Andrew D Miller,6,* Jimmy D Bell1,* 1Department of Life Sciences, Faculty of Science and Technology, University of Westminster, 2CR-UK Clinical MR Research Group, Institute of Cancer Research, Sutton, Surrey, 3Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, 4Department of Medicine, Division of Experimental Medicine, Centre for Pharmacology & Therapeutics, Toxicology Unit, Imperial College London, 5Faculty of Medicine, Nutrition and Dietetic Research Group, Division of Diabetes, Endocrinology and Metabolism, Department of Investigative Medicine, Imperial College London, Hammersmith Hospital, 6Institute of Pharmaceutical Science, King’s College London, London, UK *These authors contributed equally to this work Abstract: Metabolic reengineering using nanoparticle delivery represents an innovative therapeutic approach to normalizing the deregulation of cellular metabolism underlying many diseases, including cancer. Here, we demonstrated a unique and novel application to the treatment of malignancy using a short-chain fatty acid (SCFA-encapsulated lipid-based delivery system – liposome-encapsulated acetate nanoparticles for cancer applications (LITA-CAN. We assessed chronic in vivo administration of our nanoparticle in three separate murine models of colorectal cancer. We demonstrated a substantial reduction in tumor growth in the xenograft model of colorectal cancer cell lines HT-29, HCT-116 p53+/+ and HCT-116 p53-/-. Nanoparticle-induced reductions in histone deacetylase gene expression indicated a potential mechanism for these anti-proliferative effects. Together, these results indicated that LITA-CAN could be used as an effective direct or adjunct therapy to treat malignant transformation in vivo. Keywords: lipid-based nanoparticles, liposomes

  9. The combination of cannabidiol and Δ9-tetrahydrocannabinol enhances the anticancer effects of radiation in an orthotopic murine glioma model.

    Science.gov (United States)

    Scott, Katherine A; Dalgleish, Angus G; Liu, Wai M

    2014-12-01

    High-grade glioma is one of the most aggressive cancers in adult humans and long-term survival rates are very low as standard treatments for glioma remain largely unsuccessful. Cannabinoids have been shown to specifically inhibit glioma growth as well as neutralize oncogenic processes such as angiogenesis. In an attempt to improve treatment outcome, we have investigated the effect of Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) both alone and in combination with radiotherapy in a number of glioma cell lines (T98G, U87MG, and GL261). Cannabinoids were used in two forms, pure (P) and as a botanical drug substance (BDS). Results demonstrated a duration- and dose-dependent reduction in cell viability with each cannabinoid and suggested that THC-BDS was more efficacious than THC-P, whereas, conversely, CBD-P was more efficacious than CBD-BDS. Median effect analysis revealed all combinations to be hyperadditive [T98G 48-hour combination index (CI) at FU50, 0.77-1.09]. Similarly, pretreating cells with THC-P and CBD-P together for 4 hours before irradiation increased their radiosensitivity when compared with pretreating with either of the cannabinoids individually. The increase in radiosensitivity was associated with an increase in markers of autophagy and apoptosis. These in vitro results were recapitulated in an orthotopic murine model for glioma, which showed dramatic reductions in tumor volumes when both cannabinoids were used with irradiation (day 21: 5.5 ± 2.2 mm(3) vs. 48.7 ± 24.9 mm(3) in the control group; P < 0.01). Taken together, our data highlight the possibility that these cannabinoids can prime glioma cells to respond better to ionizing radiation, and suggest a potential clinical benefit for glioma patients by using these two treatment modalities. ©2014 American Association for Cancer Research.

  10. Anti-cancer effects of Ajwa dates (Phoenix dactylifera L.) in diethylnitrosamine induced hepatocellular carcinoma in Wistar rats.

    Science.gov (United States)

    Khan, Fazal; Khan, Tariq Jamal; Kalamegam, Gauthaman; Pushparaj, Peter Natesan; Chaudhary, Adeel; Abuzenadah, Adel; Kumosani, Taha; Barbour, Elie; Al-Qahtani, Mohammed

    2017-08-22

    Hepatocellular carcinoma (HCC) accounts for major cancer-related deaths despite current advanced therapies. Treatment and prognosis of HCC is better in patients with preserved liver function. Many natural products including ajwa dates (Phoenix dactylifera L.), are claimed to have hepatoprotective and HCC inhibitory effects, but most lack scientific validation. To prove our hypothesis, we attempted to evaluate the HCC inhibitory effects, and other beneficial properties of the aqueous extract of ajwa dates (ADE) in a rat model of diethylnitrosamine (DEN) induced liver cancer. Thirty-two male rats were divided into four groups of eight each as follows, Group A: untreated control; Group B: DEN control (180 mg/kg bw), Group C: DEN + ADE 0.5 g/kg bw; and Group D: DEN +1.0 g/kg bw. Rats from all groups were assessed for liver cancer progression or inhibition by evaluating histological, biochemical, antioxidant enzyme status, cytokines and gene expression profiles. DEN treatment Groups (B, C, D) showed histological features of HCC and in rats treated with ADE (Groups C, D) partial to complete reversal of normal liver architecture was observed. Antioxidant enzymes such as superoxide dismutase (SOD), glutathione reductase (GR), glutatione peroxidase (GPx) and catalase (CAT) were increased, while the liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels and lipid peroxidation were significantly decreased in Group C and Group D compared to Group B. Pro-inflammatory cytokines such as interleukin (IL)-1α, IL-1β,, GM-CSF) were increased in the serum of rats in Group B while the anti-tumor cytokines (IL-2, IL-12) were increased in ADE treated Groups (C, D). In addition, Alpha-Feto Protein (AFP) and IL-6 gene expression levels were upregulated in Group B, while they were significantly downregulated in ADE treated Groups (C, D). ADE helped in the reversal of DEN damaged liver towards normal. Restoration of anti

  11. Anti-cancer effects of newly developed chemotherapeutic agent, glycoconjugated palladium (II) complex, against cisplatin-resistant gastric cancer cells

    International Nuclear Information System (INIS)

    Tanaka, Mamoru; Kamiya, Takeshi; Joh, Takashi; Kataoka, Hiromi; Yano, Shigenobu; Ohi, Hiromi; Kawamoto, Keisuke; Shibahara, Takashi; Mizoshita, Tsutomu; Mori, Yoshinori; Tanida, Satoshi

    2013-01-01

    Cisplatin (CDDP) is the most frequently used chemotherapeutic agent for various types of advanced cancer, including gastric cancer. However, almost all cancer cells acquire resistance against CDDP, and this phenomenon adversely affects prognosis. Thus, new chemotherapeutic agents that can overcome the CDDP-resistant cancer cells will improve the survival of advanced cancer patients. We synthesized new glycoconjugated platinum (II) and palladium (II) complexes, [PtCl 2 (L)] and [PdCl 2 (L)]. CDDP-resistant gastric cancer cell lines were established by continuous exposure to CDDP, and gene expression in the CDDP-resistant gastric cancer cells was analyzed. The cytotoxicity and apoptosis induced by [PtCl 2 (L)] and [PdCl 2 (L)] in CDDP-sensitive and CDDP-resistant gastric cancer cells were evaluated. DNA double-strand breaks by drugs were assessed by evaluating phosphorylated histone H2AX. Xenograft tumor mouse models were established and antitumor effects were also examined in vivo. CDDP-resistant gastric cancer cells exhibit ABCB1 and CDKN2A gene up-regulation, as compared with CDDP-sensitive gastric cancer cells. In the analyses of CDDP-resistant gastric cancer cells, [PdCl 2 (L)] overcame cross-resistance to CDDP in vitro and in vivo. [PdCl 2 (L)] induced DNA double-strand breaks. These results indicate that [PdCl 2 (L)] is a potent chemotherapeutic agent for CDDP-resistant gastric cancer and may have clinical applications

  12. Effects of particle size and surface coating on cellular uptake of polymeric nanoparticles for oral delivery of anticancer drugs.

    Science.gov (United States)

    Win, Khin Yin; Feng, Si-Shen

    2005-05-01

    This study evaluated cellular uptake of polymeric nanoparticles by using Caco-2 cells, a human colon adenocarcinoma cell line, as an in vitro model with the aim to apply nanoparticles of biodegradable polymers for oral chemotherapy. The feasibility was demonstrated by showing the localization and quantification of the cell uptake of fluorescent polystyrene nanoparticles of standard size and poly(lactic-co-glycolic acid) (PLGA) nanoparticles coated with polyvinyl alcohol (PVA) or vitamin E TPGS. Coumarin-6 loaded PLGA nanoparticles were prepared by a modified solvent extraction/evaporation method and characterized by laser light scattering for size and size distribution, scanning electron microscopy (SEM) for surface morphology, zeta-potential for surface charge, and spectrofluorometry for fluorescent molecule release from the nanoparticles. The effects of particle size and particle surface coating on the cellular uptake of the nanoparticles were quantified by spectrofluorometric measurement. Cellular uptake of vitamin E TPGS-coated PLGA nanoparticles showed 1.4 folds higher than that of PVA-coated PLGA nanoparticles and 4-6 folds higher than that of nude polystyrene nanoparticles. Images of confocal laser scanning microscopy, cryo-SEM and transmission electron microscopy clearly evidenced the internalization of nanoparticles by the Caco-2 cells, showing that surface modification of PLGA nanoparticles with vitamin E TPGS notably improved the cellular uptake. It is highly feasible for nanoparticles of biodegradable polymers to be applied to promote oral chemotherapy.

  13. Anticancer effect of dentatin and dentatin-hydroxypropyl-β-cyclodextrin complex on human colon cancer (HT-29 cell line

    Directory of Open Access Journals (Sweden)

    AL-Abboodi AS

    2017-11-01

    Full Text Available Ashwaq Shakir AL-Abboodi,1,2 Abdullah Rasedee,3 Ahmad Bustamam Abdul,1,4 Yun Hin Taufiq-Yap,5 Wafaa Abd Alwahed Alkaby,6 Mostafa Saddam Ghaji,7 Peter M Waziri,1,8 Mothanna Sadiq Al-Qubaisi1 1MAKNA-UPM, Cancer Research Laboratory, Institute of Bioscience, University Putra Malaysia, Serdang, Malaysia; 2Basic Science Branch, Faculty of Dentistry, University of Al-Qadisiyah, Al Diwaniyah, Iraq; 3Department of Veterinary Laboratory Diagnosis, Faculty of Veterinary Medicine, University Putra Malaysia, Serdang, Malaysia; 4Department of Biomedical Science, Faculty of Medicine and Health Science, University Putra Malaysia, Serdang, Malaysia; 5Department of Chemistry, Faculty of Science, University Putra Malaysia, Serdang, Malaysia; 6Department of Biomedical, Faculty of Biotechnology, University of AL-Qadisiyah, Al Diwaniyah, Iraq; 7Department of Anatomy and Histology, Faculty of Veterinary Medicine, University of Basrah, Basrah, Iraq; 8Department of Biochemistry, Kaduna State University, Main Campus,  Kaduna, Nigeria Introduction: Dentatin (DEN (5-methoxy-2, 2-dimethyl-10-(1, 1-dimethyl-2propenyl dipyran-2-one, a natural compound present in the roots of Clausena excavata Burm f, possesses pro-apoptotic and antiproliferative effects in various cancer cells. Because of its hydrophobicity, it is believed that its complexation with hydroxy-β-cyclodextrin (HPβCD will make it a potent inhibitor of cancer cell growth. In the current work, the molecular mechanisms of apoptosis induced by DEN and DEN-HPβCD complex were demonstrated in human colon HT-29 cancer cells.Materials and methods: After the human colon HT-29 cancer cells were treated with DEN and DEN-HPβCD complex, their effects on the expression of apoptotic-regulated gene markers in mitochondria-mediated apoptotic and death receptor pathways were detected by Western blot analysis and reverse transcription polymerase chain reaction. These markers included caspases-9, 3, and 8, cytochrome c, poly (ADP

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

    Science.gov (United States)

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

    2013-03-01

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

  15. Green tea phytocompounds as anticancer: A review

    Directory of Open Access Journals (Sweden)

    Najeeb Ullah

    2016-04-01

    Full Text Available Green tea is universally considered significant and its benefits have been experimentally explored by researchers and scientists. Anticancer potential of green tea has been completely recognized now. Green tea contains anti-cancerous constituents and nutrients that have powerful remedial effects. By using electronic data base (1998–2015, different compounds in green tea possessing anticancer activity including epigallocatechin-3-gallate, paclitaxel and docetaxel combinations, ascorbic acid, catechins, lysine, synergistic arginine, green tea extract, proline, and green tea polyphenols has been reported. Green tea extracts exhibited remedial potential against cancer of lung, colon, liver, stomach, leukemic cells, prostate, breast, human cervical cells, head, and neck. For centuries, green tea has been utilized as medicine for therapeutic purposes. It originated in China and extensively used in Asian countries for blood pressure depression and as anticancer medicine. Green tea has therapeutic potential against many diseases such as lowering of blood pressure, Parkinson’s disease, weight loss, esophageal disease, skin-care, cholesterol, Alzheimer’s disease and diabetes.

  16. Histone Deacetylase Inhibitors as Anticancer Drugs

    Directory of Open Access Journals (Sweden)

    Tomas Eckschlager

    2017-07-01

    Full Text Available Carcinogenesis cannot be explained only by genetic alterations, but also involves epigenetic processes. Modification of histones by acetylation plays a key role in epigenetic regulation of gene expression and is controlled by the balance between histone deacetylases (HDAC and histone acetyltransferases (HAT. HDAC inhibitors induce cancer cell cycle arrest, differentiation and cell death, reduce angiogenesis and modulate immune response. Mechanisms of anticancer effects of HDAC inhibitors are not uniform; they may be different and depend on the cancer type, HDAC inhibitors, doses, etc. HDAC inhibitors seem to be promising anti-cancer drugs particularly in the combination with other anti-cancer drugs and/or radiotherapy. HDAC inhibitors vorinostat, romidepsin and belinostat have been approved for some T-cell lymphoma and panobinostat for multiple myeloma. Other HDAC inhibitors are in clinical trials for the treatment of hematological and solid malignancies. The results of such studies are promising but further larger studies are needed. Because of the reversibility of epigenetic changes during cancer development, the potency of epigenetic therapies seems to be of great importance. Here, we summarize the data on different classes of HDAC inhibitors, mechanisms of their actions and discuss novel results of preclinical and clinical studies, including the combination with other therapeutic modalities.

  17. Morpholine or methylpiperazine and salicylaldimine based heteroleptic square planner platinum (II) complexes: In vitro anticancer study and growth retardation effect on E. coli.

    Science.gov (United States)

    Rahman, Faiz-Ur; Ali, Amjad; Khan, Inam Ullah; Duong, Hong-Quan; Yu, Shang-Bo; Lin, Yue-Jian; Wang, Hui; Li, Zhan-Ting; Zhang, Dan-Wei

    2017-05-05

    Morpholine and methylpiperazine are among the most important structural parts of different drugs including organic chemotherapeutic agents. In the current study we incorporated these entities as co-ligand and a series of structurally related mono- and di-metallic square planner Pt(II) complexes (Pt(II)(salicylaldimine)(morpholine)Cl C1a-C3a, Pt(II)(salicylaldimine) (methylpiperazine)Cl C1b-C3b, di-metallic Pt(II) 2 (bis-salicylaldimine)(morpholine) 2 Cl 2 C4a and Pt(II) 2 (bis-salicylaldimine)(methylpiperazine) 2 Cl 2 C4b were prepared. These complexes were characterized by 1 H, 13 C, 19 F, 2D NOESY NMR, HR ESI-MS and elemental analyses, while structures of C2a, C3a and C4b were determined by single crystal X-ray analysis. All these complexes were studied for their in vitro cytotoxic effect on breast (MCF-7), liver (HepG2) and lung (A549) cancer cell lines. All these complexes showed considerable cytotoxic effect on these tested cancer cell lines comparable to cisplatin. Moreover three complexes C1a, C4a and C1b were studied in details. Time- and dose-dependent study was performed for C1a, C4a and C1b. These complexes induced the expression of p53 that suppresses cancer cell growth. Induction of PUMA gene and repression of MYC oncogene suggested that these complexes targeted different genes to suppress cancer progression. TUNEL assay showed induction of apoptosis and invasion analysis showed reduction in invasion ability of breast cancer cells treated with C1a, C4a or C1b. Importantly, these novel complexes suppressed the expression of EMT and metastasis promoter genes. Similarly these complexes induced autophagy by enhancing the expression of autophagy related genes such as beclin, atg-5 and atg-7. The E. coli growth retardation study showed stronger growth inhibitory effects and subsequently resulted in filamentous morphology of bacterial cells. Gel electrophoresis study proved the interaction of these complexes with DNA. All these analysis revealed anticancer

  18. 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.

  19. 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

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

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    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.

  1. 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.

  2. Synthesis of Triazole Derivatives of Levoglucosenone As Promising Anticancer Agents: Effective Exploration of the Chemical Space through retro-aza-Michael//aza-Michael Isomerizations.

    Science.gov (United States)

    Tsai, Yi-Hsuan; Borini Etichetti, Carla M; Di Benedetto, Carolina; Girardini, Javier E; Martins, Felipe Terra; Spanevello, Rolando A; Suárez, Alejandra G; Sarotti, Ariel M

    2018-03-08

    The design and synthesis of biomass-derived triazoles and the in vitro evaluation as potential anticancer agents are described. The discovery of base-catalyzed retro-aza-Michael//aza-Michael isomerizations allowed the exploration of the chemical space by affording novel types of triazoles, difficult to obtain otherwise. Following this strategy, 2,4-disubstituted 1,2,3-triazoles could be efficiently obtained from the corresponding 1,4-disubstituted analogues.

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

    OpenAIRE

    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

    2010-01-01

    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...

  4. Nanomedicine-based combination anticancer therapy between nucleic acids and small-molecular drugs.

    Science.gov (United States)

    Huang, Wei; Chen, Liqing; Kang, Lin; Jin, Mingji; Sun, Ping; Xin, Xin; Gao, Zhonggao; Bae, You Han

    2017-06-01

    Anticancer therapy has always been a vital challenge for the development of nanomedicine. Repeated single therapeutic agent may lead to undesirable and severe side effects, unbearable toxicity and multidrug resistance due to complex nature of tumor. Nanomedicine-based combination anticancer therapy can synergistically improve antitumor outcomes through multiple-target therapy, decreasing the dose of each therapeutic agent and reducing side effects. There are versatile combinational anticancer strategies such as chemotherapeutic combination, nucleic acid-based co-delivery, intrinsic sensitive and extrinsic stimulus combinational patterns. Based on these combination strategies, various nanocarriers and drug delivery systems were engineered to carry out the efficient co-delivery of combined therapeutic agents for combination anticancer therapy. This review focused on illustrating nanomedicine-based combination anticancer therapy between nucleic acids and small-molecular drugs for synergistically improving anticancer efficacy. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Anticancer agents from marine sponges.

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

    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 approach for the synthesis of highly water-dispersible functionalized graphene nanosheets, suggesting a possibility of replacing toxic hydrazine by a natural and safe phenolic

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

    Directory of Open Access Journals (Sweden)

    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

  8. Developing Exposure/Response Models for Anticancer Drug Treatment: Special Considerations

    OpenAIRE

    Mould, DR; Walz, A-C; Lave, T; Gibbs, JP; Frame, B

    2015-01-01

    Anticancer agents often have a narrow therapeutic index (TI), requiring precise dosing to ensure sufficient exposure for clinical activity while minimizing toxicity. These agents frequently have complex pharmacology, and combination therapy may cause schedule-specific effects and interactions. We review anticancer drug development, showing how integration of modeling and simulation throughout development can inform anticancer dose selection, potentially improving the late-phase success rate. ...

  9. Developing Exposure/Response Models for Anticancer Drug Treatment: Special Considerations

    Science.gov (United States)

    Mould, DR; Walz, A-C; Lave, T; Gibbs, JP; Frame, B

    2015-01-01

    Anticancer agents often have a narrow therapeutic index (TI), requiring precise dosing to ensure sufficient exposure for clinical activity while minimizing toxicity. These agents frequently have complex pharmacology, and combination therapy may cause schedule-specific effects and interactions. We review anticancer drug development, showing how integration of modeling and simulation throughout development can inform anticancer dose selection, potentially improving the late-phase success rate. This article has a companion article in Clinical Pharmacology & Therapeutics with practical examples. PMID:26225225

  10. TAS1R3 and UCN2 Transcript Levels in Blood Cells Are Associated With Sugary and Fatty Food Consumption in Children.

    Science.gov (United States)

    Priego, T; Sánchez, J; Picó, C; Ahrens, W; De Henauw, S; Kourides, Y; Lissner, L; Molnár, D; Moreno, L A; Russo, P; Siani, A; Veidebaum, T; Palou, A

    2015-09-01

    New types of dietary exposure biomarkers are needed to implement effective strategies for obesity prevention in children. Of special interest are biomarkers of consumption of food rich in simple sugars and fat because their intake has been associated with obesity development. Peripheral blood cells (PBCs) represent a promising new tool for identifying novel, transcript-based biomarkers. This study aimed to study potential associations between the transcripts of taste receptor type 1 member 3 (TAS1R3) and urocortin II (UCN2) genes in PBCs and the frequency of sugary and fatty food consumption in children. Four hundred sixty-three children from the IDEFICS cohort were selected to include a similar number of boys and girls, both normal-weight and overweight, belonging to eight European countries. Anthropometric parameters (measured at baseline and in a subset of 193 children after 2 years), food consumption frequency and transcript levels of TAS1R3 and UCN2 genes in PBCs were measured. Children with low-frequency consumption of sugary foods displayed higher TAS1R3 expression levels with respect to those with intermediate or high frequency. In turn, children with high-frequency consumption of fatty foods showed lower UCN2 expression levels with respect to those with low or intermediate frequency. Moreover, transcripts of TAS1R3 were related with body mass index and fat-mass changes after a 2-year follow-up period, with low expression levels of this gene being related with increased fat accumulation over time. The transcripts of TAS1R3 and UCN2 in PBCs may be considered potential biomarkers of consumption of sugary and fatty food, respectively, to complement data of food-intake questionnaires.

  11. Phytochemicals as Adjunctive with Conventional Anticancer Therapies.

    Science.gov (United States)

    Farzaei, Mohammad Hosein; Bahramsoltani, Roodabeh; Rahimi, Roja

    2016-01-01

    Cancer is defined as the abnormal proliferations of cells which could occur in any tissue and can cause life-threatening malignancies with high financial costs for both patients and health care system. Plant-derived secondary metabolites are shown to have positive role in various diseases and conditions. The aim of the present study is to summarize clinical evidences on the benefits of phytochemicals as adjuvant therapy along with conventional anticancer therapies. Electronic databases including Pubmed, Scopus and Cochrane library were searched with the keywords "chemotherapeutic", "anticancer", "antineoplastic" or "radiotherapy" with "plant", "extract", "herb", or "phytochemical", until July 2015. Only clinical studies were included in this review. The findings showed that positive effects of phytochemicals are due to their direct anticarcinogenic activity, induction of relief in cancer complications, as well as their protective role against side effects of conventional chemotherapeutic agents. Results obtained from current review demonstrated that numerous phytochemical agents from different chemical categories including alkaloid, benzopyran, coumarin, carotenoid, diarylheptanoid, flavonoid, indole, polysaccharide, protein, stilbene, terpene, and xanthonoid possess therapeutic effect in patients with different types of cancer. Polyphenols are the most studied components. Curcumin, ginsenosides, lycopene, homoharringtonine, aviscumine, and resveratrol are amongst the major components with remarkable volumes of clinical evidence indicating their direct anticancer activities in different types of cancer including hepatocarcinoma, prostate cancer, leukemia and lymphoma, breast and ovarian cancer, and gastrointestinal cancers. Cannabinoids, cumarin, curcumin, ginsenosides, epigallocatechin gallate, vitexin, and salidroside are phytochemicals with significant alleviative effect on synthetic chemotherapy- induced toxicities. There is lack of evidence from clinical

  12. 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

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

    International Nuclear Information System (INIS)

    Hayashida, Shigeaki; Hirasawa, Teruyuki; Uchiyama, Kouichi; Mitsui, Hiroshi; Nasu, Takahito; Shinohara, Youichi

    1995-01-01

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

  14. Anti-cancer activities of Ganoderma lucidum: active ingredients and pathways

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    Chi H.J. Kao

    2013-02-01

    Full Text Available ABSTRACTGanoderma lucidum, commonly referred to as Lingzhi, has been used in Asia for health promotion for centuries. The anti-cancer effects of G. lucidum have been demonstrated in both in vitro and in vivo studies. In addition, the observed anti-cancer activities of Ganoderma have prompted its usage by cancer patients alongside chemotherapy.The main two bioactive components of G. lucidum can be broadly grouped into triterpenes and polysaccharides. Despite triterpenes and polysaccharides being widely known as the major active ingredients, the different biological pathways by which they exert their anti-cancer effect remain poorly defined. Therefore, understanding the mechanisms of action may lead to more widespread use of Ganoderma as an anti-cancer agent.The aim of this paper is to summarise the various bioactive mechanisms that have been proposed for the anti-cancer properties of triterpenes and polysaccharides extracted from G. lucidum. A literature search of published papers on NCBI with keywords “Ganoderma” and “cancer” was performed. Among those, studies which specifically examined the anti-cancer activities of Ganoderma triterpenes and polysaccharides were selected to be included in this paper.We have found five potential mechanisms which are associated with the anti-cancer activities of Ganoderma triterpenes and three potential mechanisms for Ganoderma polysaccharides. In addition, G. lucidum has been used in combination with known anti-cancer agents to improve the anti-cancer efficacies. This suggests Ganoderma’s bioactive pathways may compliment that of anti-cancer agents. In this paper we present several potential anti-cancer mechanisms of Ganoderma triterpenes and polysaccharides which can be used for the development of Ganoderma as an anti-cancer agent.

  15. TAILORING IMMUNOTOXIN AS ANTICANCER DRUG

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    Santoso Cornain

    2012-09-01

    Full Text Available The conventional treatments for cancer have been considered unsatisfatory, with limited efficiency in terms of discriminative cancer cell adverse reaction against the normal compartments, a number of immunological approaches had been implemented. Since cancer cells could exhibit tumor specific antigen (s, a highly specific antibody could be used to direct any anticancer drug, biological agent or radioisotope selectively against the cancer cells and does not harm the normal cells. The specific antibody could be raised by immunization with purified tumor specific antigen (s. The biological agent could be obtained as toxin, either derived from bacteria e.g. diphtheria toxin or derived from plants e.g. castor ricin, which could destroy and kill cancer cells after contacts. A hybrid molecule constructed between antibody and toxin has been known as "immunotoxin". The selectivity of the antibody against a given tumor specific antigen could be increased by using a monoclonal antibody, made by hybridoma technique and immunological engineering. Accordingly, the efficiency of the destructive or killing effect of the toxin could be eventually increased by purification technique, biochemical and genetic engineering. In a preliminary study ricin from castor (Ricinus communis have been purified and separated into two protein fractions (RCAI = 12.000 dalton and RCA II = 60.000 - 65.000 dalton. The latter showed toxin property, and was tested in vitro both against normal cells and against cancer cells. In the microcy totoxicity assay the ricin showed both the short term and the long term killing effect as measured after 1, 4, 16 and 24 hours. The killing effect against cancer cells was stronger as compared to that against normal cells. The acute or short term effect was observed at lower concentration of ricin (10-6 and 10-12 g/ml after 1 and 4 hours contacts. The long term effect resulted in 90% and nearly 100% cytotoxicity in higher concentration of ricin

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

    International Nuclear Information System (INIS)

    Turanek, Jaroslav; Wang Xiufang; Knoetigova, Pavlina; Koudelka, Stepan; Dong Lanfeng; Vrublova, Eva; Mahdavian, Elahe; Prochazka, Lubomir; Sangsura, Smink; Vacek, Antonin; Salvatore, Brian A.; Neuzil, Jiri

    2009-01-01

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

  17. Relationship between Antioxidant and Anticancer Activity of Trihydroxyflavones

    Directory of Open Access Journals (Sweden)

    Ignas Grigalius

    2017-12-01

    Full Text Available Plant polyphenols have been highlighted not only as chemopreventive, but also as potential anticancer substances. Flavones are a subclass of natural flavonoids reported to have an antioxidant and anticancer activity. The aim of our study was to evaluate antioxidant and anticancer activity of seventeen trihydroxyflavone derivatives, including apigenin (API and baicalein (BCL. Also, we wanted to find out if there is a correlation between those two effects. Cell growth inhibition testing was carried out using MTT assay in three different human cancer cell lines: lung (A549, breast (MCF-7 and brain epithelial (U87. Antioxidant activity was determined by the DPPH radical scavenging method. Thirteen trihydroxyflavones possessed anticancer activity against at least one tested cancer cell line. They were more active against the MCF-7 cell line, and the lowest activity was determined against the U87 cell line. The majority of compounds inhibited cancer cell growth at EC50 values between 10–50 µM. The most active compound was 3’,4’,5-trihydroxyflavone 7, especially against A549 and MCF-7 cell lines. The correlation between anti-proliferative and antioxidant activity was only moderate, and it was determined for A549 and U87 cancer cell lines. The most important fragment for those two effects is the ortho-dihydroxy group in ring B. Conclusions. Trihydroxyflavones demonstrated anticancer activity. Further and more detailed studies should to be carried out to estimate the structure–activity relationship of these compounds.

  18. Current evidence on the anticancer potential of Chios mastic gum.

    Science.gov (United States)

    Giaginis, Constantinos; Theocharis, Stamatios

    2011-11-01

    Chios mastic gum derived from the plant Pistacia lentiscus L. variation chia has been shown to exert beneficial effects on a wide range of human disorders. The most comprehensive data so far have indicated that mastic gum provides protection against gastrointestinal malfunctions and bacterial infections. Substantial evidence has also suggested that mastic gum exhibits hepatoprotective and cardioprotective, antiinflammatory/antioxidant, and antiatherogenic properties. In the last decade, an increasing number of studies further evaluated the potential antiproliferative properties of mastic gum against several types of human neoplasia. The present review aims to summarize the current data concerning the anticancer activities of mastic gum and their major constituents, highlighting also the molecular mechanisms through which they exert anticancer function. Mastic gum constituents that belong to the chemical class of triterpenoids appear to be mainly responsible for its anticancer potential. Thus, a brief discussion is dedicated to the anticancer activity of synthetic and naturally occurring triterpenoid analogues with similar chemical structure to mastic gum constituents. Taking into consideration the available data so far, Chios mastic gum could be considered as a conglomeration of effective anticancer drugs.

  19. Exploring the influence of culture conditions on kefir's anticancer properties.

    Science.gov (United States)

    Hatmal, Ma'mon M; Nuirat, Abeer; Zihlif, Malek A; Taha, Mutasem O

    2018-05-01

    Cancer is a major health problem in many parts of the world. Conventional anticancer treatments are painful, expensive, and unsafe. Therefore, demand is increasing for cancer treatments preferentially in the form of functional foods or nutritional supplements. Kefir, a traditional fermented milk dairy product, has significant antimutagenic and antitumor properties. This research addresses the hypothesis that kefir's anticancer properties are affected by fermentation conditions. Initially, kefir extracts prepared under standard conditions were screened against 7 cancer cell lines using the tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. Colon cancer and chronic myelogenous leukemia cells were found to be most susceptible to kefir extracts. Subsequently, a factorial design was implemented to assess the effects of 3 fermentation times (24, 48, and 72 h), 3 kefir-to-milk ratios (2, 5, and 10% wt/vol), and 3 fermentation temperatures (4, 25, and 40°C) on kefir's anticancer properties. Remarkably, exploration of the fermentation conditions allowed the anticancer properties of kefir to be enhanced by 5- to 8-fold against susceptible cell lines. Overall, these results demonstrate the possibility of optimizing the anticancer properties of kefir as a functional food in cancer therapy. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  20. Recent discoveries of anticancer flavonoids.

    Science.gov (United States)

    Raffa, Demetrio; Maggio, Benedetta; Raimondi, Maria Valeria; Plescia, Fabiana; Daidone, Giuseppe

    2017-12-15

    In this review we report the recent advances in anticancer activity of the family of natural occurring flavonoids, covering the time span of the last five years. The bibliographic data will be grouped, on the basis of biological information, in two great categories: reports in which the extract plants bioactivity is reported and the identification of each flavonoid is present or not, and reports in which the anticancer activity is attributable to purified and identified flavonoids from plants. Wherever possible, the targets and mechanisms of action as well as the structure-activity relationships of the molecules will be reported. Also, in the review it was thoroughly investigated the recent discovery on flavonoids containing the 2-phenyl-4H-chromen-4-one system even if some examples of unusual flavonoids, bearing a non-aromatic B-ring or other ring condensed to the base structure are reported. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  1. Association of Neuropeptide Y (NPY), Interleukin-1B (IL1B) Genetic Variants and Correlation of IL1B Transcript Levels with Vitiligo Susceptibility

    Science.gov (United States)

    Laddha, Naresh C.; Dwivedi, Mitesh; Mansuri, Mohmmad Shoab; Singh, Mala; Patel, Hetanshi H.; Agarwal, Nishtha; Shah, Anish M.; Begum, Rasheedunnisa

    2014-01-01

    Background Vitiligo is a depigmenting disorder resulting from loss of functional melanocytes in the skin. NPY plays an important role in induction of immune response by acting on a variety of immune cells. NPY synthesis and release is governed by IL1B. Moreover, genetic variability in IL1B is reported to be associated with elevated NPY levels. Objectives Aim of the present study was to explore NPY promoter −399T/C (rs16147) and exon2 +1128T/C (rs16139) polymorphisms as well as IL1B promoter −511C/T (rs16944) polymorphism and to correlate IL1B transcript levels with vitiligo. Methods PCR-RFLP method was used to genotype NPY -399T/C SNP in 454 patients and 1226 controls; +1128T/C SNP in 575 patients and 1279 controls and IL1B −511C/T SNP in 448 patients and 785 controls from Gujarat. IL1B transcript levels in blood were also assessed in 105 controls and 95 patients using real-time PCR. Results Genotype and allele frequencies for NPY −399T/C, +1128T/C and IL1B −511C/T SNPs differed significantly (pvitiligo by 2.3 fold (pvitiligo (p = 0.015), also in female patients than male patients (p = 0.026). Genotype-phenotype correlation showed moderate association of IL1B -511C/T polymorphism with higher IL1B transcript levels. Trend analysis revealed significant difference between patients and controls for IL1B transcript levels with respect to different genotypes. Conclusion Our results suggest that NPY −399T/C, +1128T/C and IL1B −511C/T polymorphisms are associated with vitiligo and IL1B −511C/T SNP influences its transcript levels leading to increased risk for vitiligo in Gujarat population. Up-regulation of IL1B transcript in patients advocates its possible role in autoimmune pathogenesis of vitiligo. PMID:25221996

  2. 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.

  3. 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.

  4. Neurological complications of medical anti-cancer therapies

    Directory of Open Access Journals (Sweden)

    Jerzy Hildebrand

    2011-12-01

    Full Text Available This review describes the features of central and peripheral neurological disorders caused by anti-cancer chemotherapy and supportive medications, such as antiepileptic drugs, glucocorticosteroids and opioids, frequently used in cancer patients. Diffuse encephalopathy with or without epileptic seizures, cerebellar disorders and aseptic meningitis may occur after systemic administration of conventional drug doses, but their incidence is much higher when either high-dose chemotherapy, or intrathecal or intracarotid administration is used. Spinal cord and/or spinal root lesions have been reported after intrathecal administration of methotrexate or cytosinearabinoside. Anti-cancer chemotherapy is the leading cause of peripheral neuropathy in cancer patients. The main culprits are vinca alkaloids, platinum derivatives and taxanes. Anti-cancer chemotherapy has no significant toxic effect on muscle tissue, but heavy administration of glucocorticosteroids is a common cause of disabling, predominantly pelvic, muscle atrophy.

  5. Investigating the optimal size of anticancer nanomedicine.

    Science.gov (United States)

    Tang, Li; Yang, Xujuan; Yin, Qian; Cai, Kaimin; Wang, Hua; Chaudhury, Isthier; Yao, Catherine; Zhou, Qin; Kwon, Mincheol; Hartman, James A; Dobrucki, Iwona T; Dobrucki, Lawrence W; Borst, Luke B; Lezmi, Stéphane; Helferich, William G; Ferguson, Andrew L; Fan, Timothy M; Cheng, Jianjun

    2014-10-28

    Nanomedicines (NMs) offer new solutions for cancer diagnosis and therapy. However, extension of progression-free interval and overall survival time achieved by Food and Drug Administration-approved NMs remain modest. To develop next generation NMs to achieve superior anticancer activities, it is crucial to investigate and understand the correlation between the physicochemical properties of NMs (particle size in particular) and their interactions with biological systems to establish criteria for NM optimization. Here, we systematically evaluated the size-dependent biological profiles of three monodisperse drug-silica nanoconjugates (NCs; 20, 50, and 200 nm) through both experiments and mathematical modeling and aimed to identify the optimal size for the most effective anticancer drug delivery. Among the three NCs investigated, the 50-nm NC shows the highest tumor tissue retention integrated over time, which is the collective outcome of deep tumor tissue penetration and efficient cancer cell internalization as well as slow tumor clearance, and thus, the highest efficacy against both primary and metastatic tumors in vivo.

  6. 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.

    2017-02-01

    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 towards intracellular targets, which increases their success comparatively to specific one-target 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.

  7. Immunomodulatory and anticancer protein hydrolysates (peptides) from food proteins: A review.

    Science.gov (United States)

    Chalamaiah, Meram; Yu, Wenlin; Wu, Jianping

    2018-04-15

    Bioactive peptides are oligopeptides that consist of 2-20 amino acids that can exert beneficial effects on human health in addition to basic nutritional effects. Food derived protein hydrolysates or peptides with immunomodulatory and anticancer activities have been reported from a variety of food protein sources such as milk, egg, fish, rice, soybean, pea, chlorella, spirulina, oyster and mussel. In vitro hydrolysis of food proteins using commercial proteolytic enzymes is the most commonly employed process for the production of immunomodulatory and anticancer food protein hydrolysates. The immunomodulatory and anticancer activities of food derived protein hydrolysates or peptides are related to the amino acid composition, sequence and length. Most immunomodulatory and anticancer food protein hydrolysates or peptides were tested using cell culture and animal models, while a few involved clinical trials. This review provides a comprehensive overview of immunomodulatory and anticancer food derived protein hydrolysates or peptides, their production and mechanisms of action. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Anti-cancer Effects of a Novel Quinoline Derivative 83b1 on Human Esophageal Squamous Cell Carcinoma through Down-Regulation of COX-2 mRNA and PGE2.

    Science.gov (United States)

    Pun, Ivan Ho Yuen; Chan, Dessy; Chan, Sau Hing; Chung, Po Yee; Zhou, Yuan Yuan; Law, Simon; Lam, Alfred King Yin; Chui, Chung Hin; Chan, Albert Sun Chi; Lam, Kim Hung; Tang, Johnny Cheuk On

    2017-01-01

    83b1 is a novel quinoline derivative that has been shown to inhibit cancer growth in human esophageal squamous cell carcinoma (ESCC). This study was conducted to comprehensively evaluate the cytotoxic effects of 83b1 on a series of ESCC cell lines and investigate the mechanisms by which 83b1 suppresses cancer growth based on molecular docking analysis. A series of ESCC and nontumor immortalized cell lines were exposed to 83b1 and cisplatin (CDDP) in a dose-dependent manner, and the cytotoxicity was examined by a MTS assay kit. Prediction of the molecular targets of 83b1 was conducted by molecular docking analysis. Expression of cyclooxygenase 2 (COX-2) mRNA and COX-2-derived prostaglandin E 2 (PGE 2 ) were measured by quantitative real-time polymerase chain reaction and enzymelinked immuno-sorbent assay, respectively. In vivo anti-tumor effect was determined using a nude mice xenografted model transplanted with an ESCC cell line, KYSE-450. 83b1 showed the significant anti-cancer effects on all ESCC cell lines compared to CDDP; however, 83b1 revealed much lower toxic effects on non-tumor cell lines than CDDP. The predicted molecular target of 83b1 is peroxisome proliferator-activated receptor delta (PPARδ), which is a widely known oncoprotein. Additionally the expression of COX-2 mRNA and COX-2-derived PGE 2 were down-regulated by 83b1 in a dose-dependent manner in ESCC cell lines. Furthermore, 83b1 was shown to significantly reduce the tumor size in nude mice xenograft. The results of this study suggest that the potential anti-cancer effects of 83b1 on human esophageal cancers occur through the possible oncotarget, PPARδ, and down-regulation of the cancer related genes and molecules.

  9. Antioxidant and Anticancer activities of yeast grown on commercial ...

    African Journals Online (AJOL)

    Antioxidant and Anticancer activities of yeast grown on commercial media. Amal S. Shahat. Abstract. The use of Synthetic antioxidants is being widely restricted because of their reported toxic and carcinogenic effects. Thus, now there is considerable interest being focused towards finding antioxidants from natural sources ...

  10. Screening of Chinese brassica species for anti-cancer sulforaphane ...

    African Journals Online (AJOL)

    Natural sulforaphane and erucin have been of increasing interest for nutraceutical and pharmaceutical industries due to their anti-cancer effect. The sulforaphane and/or erucin contents in seeds of 43 different Chinese Brassica oleracea L. varieties were analyzed by HPLC and GC-MS. Among them, 21 cultivars seed meal ...

  11. Isoflavones from Calpurnia aurea subsp. Aurea and their Anticancer ...

    African Journals Online (AJOL)

    Conclusion: The isoflavones showed moderate activity against the renal, melanoma and breast cancer cell lines tested against, with the isoflavones 2 and 5 showing the best activity of the compounds tested. These isoflavones may have a synergistic effect with other anticancer drugs. Key words: Calpurnia aurea, Fabaceae, ...

  12. Screening of Chinese brassica species for anti-cancer sulforaphane ...

    African Journals Online (AJOL)

    SERVER

    2008-01-18

    Jan 18, 2008 ... Natural sulforaphane and erucin have been of increasing interest for nutraceutical and pharmaceutical industries due to their anti-cancer effect. The sulforaphane and/or erucin contents in seeds of 43 different Chinese Brassica oleracea L. varieties were analyzed by HPLC and GC-MS. Among them, 21.

  13. Evaluation of anticancer potential of eight vegetal species from the ...

    African Journals Online (AJOL)

    Background: Eight plant species from Oaxaca, some of them used in traditional medicine, were subjected to screening of several biological activities to provide data regarding their anticancer potential, although no scientific information is available about their pharmacological effects. Materials and methods: Methanol ...

  14. Glutamic acid as anticancer agent: An overview

    OpenAIRE

    Dutta, Satyajit; Ray, Supratim; Nagarajan, K.

    2013-01-01

    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. I...

  15. Stimulation of d- and l-lactate dehydrogenases transcriptional levels in presence of diammonium hydrogen phosphate resulting to enhanced lactic acid production by Lactobacillus strain.

    Science.gov (United States)

    Singhvi, Mamata; Zendo, Takeshi; Iida, Hiroshi; Gokhale, Digambar; Sonomoto, Kenji

    2017-12-01

    The present study revealed the effect of nitrogen sources on lactic acid production and stimulation of d- and l-lactate dehydrogenases (LDH) of parent Lactobacillus lactis NCIM 2368 and its mutant RM2-24 generated after UV mutagenesis. Both the parent and mutant strains were evaluated for d-lactic acid production in control and modified media. The modified media did not show remarkable effect on lactic acid production in case of parent whereas mutant exhibited significant enhancement in d-lactic acid production along with the appearance of l-lactic acid in the broth. Both LDH activities and specific activities were found to be higher in mutant than the parent strain. These results suggested that the diammonium hydrogen phosphate in modified media triggered the expression of LDH genes leading to enhanced lactic acid production. This observation has been proved by studying the expression levels of d- and l-LDH genes of parent and mutant in control and modified media using quantitative RT-PCR technique. In case of mutant, the transcriptional levels of d-LDH and l-LDH increased ∼17 fold and ∼1.38 fold respectively in modified medium compared to the values obtained with control medium. In case of parent, no significant change in transcriptional levels of d- and l-LDH was found when the cells were grown in either control medium or modified medium. This study suggested that the mutant, RM2-24 has l-LDH gene which is expressed in presence of (NH 4 ) 2 HPO 4 resulting in l-lactic acid production. Co-production of l-lactic acid in d-lactic acid fermentation may be detrimental in the PLA production. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  16. Validation of Reference Genes for the Determination of Platelet Transcript Level in Healthy Individuals and in Patients with the History of Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Zoltán Csiki

    2013-02-01

    Full Text Available RT-qPCR is the standard method for studying changes in relative transcript level in different experimental and clinical conditions and in different tissues. No validated reference genes have been reported for the normalization of transcript level in platelets. The very low level of platelet RNA and the elimination of leukocyte contamination represented special methodological difficulties. Our aims were to apply a simple technique to separate platelets for transcript level studies, and select the most stable reference genes for platelets from healthy individuals and from patients with the history of myocardial infarction. We developed a simple, straightforward method of platelet separation for RNA isolation. Platelet activation was inhibited by using acid-citrate-dextrose for anticoagulation and by prostaglandin E1. Leukocyte contamination was eliminated by three consecutive centrifugations. Samples prepared by this method were free of leukocytes, showed no inhibition in PCR reaction and no RNA degradation. The assay demands low blood volume, which complies with the requirements of everyday laboratory routine. Seventeen potential reference genes were investigated, but eight of them were excluded during optimization. The stability of the remaining genes, EEF2, EAR, ACTB, GAPDH, ANAPC5, OAZ1, HDGF, GNAS, and CFL1, were determined by four different descriptive statistics. GAPDH, GNAS, and ACTB were shown to be the most stable genes in platelets of healthy individuals, while HDGF, GNAS, and ACTB were the most stable in platelets of patients with the history of myocardial infarction. The results confirm that data normalization needs assessment of appropriate reference genes for a particular sample set.

  17. Selenium potentiates the anticancer effect of cisplatin against oxidative stress and calcium ion signaling-induced intracellular toxicity in MCF-7 breast cancer cells: involvement of the TRPV1 channel.

    Science.gov (United States)

    Sakallı Çetin, Esin; Nazıroğlu, Mustafa; Çiğ, Bilal; Övey, İshak Suat; Aslan Koşar, Pınar

    2017-02-01

    In breast cancers, calcium signaling is a main cause of proliferation and apoptosis of breast cancer cells. Although previous studies have implicated the transient receptor potential vanilloid 1 (TRPV1) cation channel, the synergistic inhibition effects of selenium (Se) and cisplatin in cancer and the suppression of ongoing apoptosis have not yet been investigated in MCF-7 breast cancer cells. This study investigates the anticancer properties of Se through TRPV1 channel activity in MCF-7 breast cancer cell line cultures when given alone or in combination with cisplatin. The MCF-7 cells were divided into four groups: the control group, the Se-treated group (200 nM), the cisplatin-treated group (40 μM) and the Se + cisplatin-treated group. The intracellular free calcium ion concentration and current densities increased with TRPV1 channel activator capsaicin (0.01 mM), but they decreased with the TRPV1 blocker capsazepine (0.1 mM), Se, cisplatin, and Se + cisplatin incubations. However, mitochondrial membrane depolarization, apoptosis, and the caspase 3, and caspase 9 values increased in the Se-treated group and the cisplatin-treated group, although Western blot (procaspase 3 and 9) results and the cell viability levels decreased with the Se and Se + cisplatin treatments. Apoptosis and caspase-3 were further increased with the Se + cisplatin treatment. Intracellular reactive oxygen species production increased with the cisplatin treatment, but not with the Se treatment. This study's results report, for the first time, that at a cellular level, Se and cisplatin interact on the same intracellular toxic cascade, and the combination of these two drugs can result in a remarkable anticancer effect through modulation of the TRPV1.

  18. 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

  19. Molecular cytotoxic mechanisms of anticancer hydroxychalcones.

    Science.gov (United States)

    Sabzevari, Omid; Galati, Giuseppe; Moridani, Majid Y; Siraki, Arno; O'Brien, Peter J

    2004-06-30

    Chalcones are being considered as anticancer agents as they are natural compounds that are particularly cytotoxic towards K562 leukemia or melanoma cells. In this study, we have investigated phloretin, isoliquiritigenin, and 10 other hydroxylated chalcones for their cytotoxic mechanisms towards isolated rat hepatocytes. All hydroxychalcones partly depleted hepatocyte GSH and oxidized GSH to GSSG. These chalcones also caused a collapse of mitochondrial membrane potential and increased oxygen uptake. Furthermore, glycolytic or citric acid cycle substrates prevented cytotoxicity and mitochondrial membrane potential collapse. The highest pKa chalcones were the most effective at collapsing the mitochondrial membrane potential which suggests that the cytotoxic activity of hydroxychalcones are likely because of their ability to uncouple mitochondria.

  20. Kefir: a powerful probiotics with anticancer properties.

    Science.gov (United States)

    Sharifi, Mohammadreza; Moridnia, Abbas; Mortazavi, Deniz; Salehi, Mahsa; Bagheri, Marzieh; Sheikhi, Abdolkarim

    2017-09-27

    Probiotics and fermented milk products have attracted the attention of scientists from various fields, such as health care, industry and pharmacy. In recent years, reports have shown that dietary probiotics such as kefir have a great potential for cancer prevention and treatment. Kefir is fermented milk with Caucasian and Tibet origin, made from the incubation of kefir grains with raw milk or water. Kefir grains are a mixture of yeast and bacteria, living in a symbiotic association. Antibacterial, antifungal, anti-allergic and anti-inflammatory effects are some of the health beneficial properties of kefir grains. Furthermore, it is suggested that some of the bioactive compounds of kefir such as polysaccharides and peptides have great potential for inhibition of proliferation and induction of apoptosis in tumor cells. Many studies revealed that kefir acts on different cancers such as colorectal cancer, malignant T lymphocytes, breast cancer and lung carcinoma. In this review, we have focused on anticancer properties of kefir.

  1. Effect of anticancer drugs on production of transforming growth factor and expression of p53 AND Bcl-2 proteins by MCF-7 and T47D cell lines of human breast carcinoma.

    Science.gov (United States)

    Stoika, R S; Yakymovych, I A; Kashchak, N I; Boyko, M M; Korynevska, A V; Klyuchyvska, O Yu; Shafranska, G I; Yakymovych, M Ya; Zhylchuk, V Ye; Kudryavets, Yu Y; Vorontsova, A L

    2008-03-01

    To compare the capability of methotrexate, cisplatin, doxorubicine and vincristine to induce production of the transforming growth factor beta(1) (TGF-beta(1)) in two cell lines - MCF-7 and T47D - of human breast carcinoma, as well as to study sensitivity of these cells to TGF-beta(1) and mentioned anticancer drugs. ELISA for detection of TGF-beta content in conditioned culture media and Western-blot analysis of the proapoptotic p53 and antiapoptotic Bcl-2 proteins were applied. T47D cells showing higher resistance to growth inhibiting effect of TGF-beta(1) were also refractory to cisplatin. There was no difference between MCF-7 and T47D cells in their sensitivity to methotrexate and doxorubicine, although T47D cells were more sensitive to vincristine. It was found that methotrexate and vincristine did not affect TGF-beta(1) production, while doxorubicine used at a dose of 1-100 ug/ml, significantly induced TGF-beta(1) production in both cell lines. p53 expression in T47D cells was higher than in MCF-7 cells where only doxorubicin induced strongly p53 expression. It should be noted, that Bcl-2 was better expressed in MCF-7 cells, while it was almost undetectable in T47D cells. In cells of human mammary carcinoma of MCF-7 and T47D lines doxorubicine, unlike vincristine and methotrexate, in dose depending manner induces production of TGF-beta(1). TGF-beta(1) production in carcinoma cells was associated with doxorubicine-mediated p53 expression in MCF-7 cells or high basal level of p53 in T47D cells. The cells of MCF-7 line were more sensitive to growth inhibition by exogenous TGF-beta(1) and to cisplatine action than T47D cells, but there was no difference between these cell lines in sensitivity to other anticancer drugs.

  2. Anticancer effects of the engineered stem cells transduced with therapeutic genes via a selective tumor tropism caused by vascular endothelial growth factor toward HeLa cervical cancer cells.

    Science.gov (United States)

    Kim, Hye-Sun; Yi, Bo-Rim; Hwang, Kyung-A; Kim, Seung U; Choi, Kyung-Chul

    2013-10-01

    The aim of the present study was to investigate the therapeutic efficacy of genetically engineered stem cells (GESTECs) expressing bacterial cytosine deaminase (CD) and/or human interferon-beta (IFN-β) gene against HeLa cervical cancer and the migration factors of the GESTECs toward the cancer cells. Anticancer effect of GESTECs was examined in a co-culture with HeLa cells using MTT assay to measure cell viability. A transwell migration assay was performed so as to assess the migration capability of the stem cells to cervical cancer cells. Next, several chemoattractant ligands and their receptors related to a selective migration of the stem cells toward HeLa cells were determined by real-time PCR. The cell viability of HeLa cells was decreased in response to 5-fluorocytosine (5-FC), a prodrug, indicating that 5-fluorouracil (5-FU), a toxic metabolite, was converted from 5-FC by CD gene and it caused the cell death in a co-culture system. When IFN-β was additionally expressed with CD gene by these GESTECs, the anticancer activity was significantly increased. In the migration assay, the GESTECs selectively migrated to HeLa cervical cancer cells. As results of real-time PCR, chemoattractant ligands such as MCP-1, SCF, and VEGF were expressed in HeLa cells, and several receptors such as uPAR, VEGFR2, and c-kit were produced by the GESTECs. These GESTECs transduced with CD gene and IFN-β may provide a potential of a novel gene therapy for anticervical cancer treatments via their selective tumor tropism derived from VEGF and VEGFR2 expressions between HeLa cells and the GESTECs.

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

    Science.gov (United States)

    Ganogpichayagrai, Aunyachulee; Palanuvej, Chanida; Ruangrungsi, Nijsiri

    2017-01-01

    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-nitro phenyl-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 IC50 of 0.0503 and 0.5813 mg/ml, respectively, against rat α-glucosidase with the IC50 of 1.4528 and 0.4333 mg/ml, respectively, compared to acarbose with the IC50 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. PMID:28217550

  4. Natural flora and anticancer regime: milestones and roadmap.

    Science.gov (United States)

    Bhatnagar, Ira; Thomas, Noel Vinay; Kim, Se-Kwon

    2013-07-01

    Cancer has long been an area of extensive research both at the molecular as well as pharmaceutical level. However, lack of understanding of the underlying molecular signalling and the probable targets of therapeutics is a major concern in successful treatment of cancer. The situation becomes even worse, with the increasing side effects of the existing synthetic commercial drugs. Natural compounds especially those derived from plants have been best explored for their anticancer properties and most of them have been efficient against the known molecular targets of cancer. However, advent of biotechnology and resulting advances in medical arena have let to the increasing knowledge of newer carcinogenic signaling agents which has made the anticancer drug discovery even more demanding. The present review aims to bring forward the molecular mediators of cancer and compiles the plant derived anticancer agents with special emphasis on their clinical status. Since marine arena has proved to be a tremendous source of pharmaceutical agents, this review also focuses on the anticancer potential of marine plants especially algae. This is a comprehensive review covering major aspects of cancer mediation and utilization of marine flora for remediation of this deadly disease.

  5. Preclinical anticancer effectiveness of a fraction from Casearia sylvestris and its component Casearin X: in vivo and ex vivo methods and microscopy examinations.

    Science.gov (United States)

    Ferreira, Paulo Michel Pinheiro; Bezerra, Daniel Pereira; Silva, Jurandy do Nascimento; da Costa, Marcília Pinheiro; Ferreira, José Roberto de Oliveira; Alencar, Nylane Maria Nunes; Figueiredo, Ingrid Samantha Tavares de; Cavalheiro, Alberto José; Machado, Camila Maria Longo; Chammas, Roger; Alves, Ana Paula Negreiros Nunes; Moraes, Manoel Odorico de; Pessoa, Claudia

    2016-06-20

    Casearia sylvestris (Salicaceae) is found in South America and presents antiulcerogenic, cytotoxic, antimicrobial, anti-inflammatory and antihypertensive activities. To assess the in vivo and ex vivo antitumor action of a fraction with casearins (FC) and its main component - Casearin X-isolated from C. sylvestris leaves. Firstly, Sarcoma 180 bearing Swiss mice were treated with FC and Cas X for 7 days. Secondly, BALB/c nude animals received hollow fibers with colon carcinoma (HCT-116) or glioblastoma (SF-295) cells and were treated with FC for 4 days. On 5th day, proliferation was determined by MTT assay. FC 10 and 25mg/kg/day i.p. and 50mg/kg/day oral and Cas X 25mg/kg/day i.p. and 50mg/kg/day oral revealed tumor growth inhibition rates of 35.8, 86.2, 53.7, 90.0 and 65.5% and such tumors demonstrated rare mitoses and coagulation necrosis areas. Similarly, FC reduced multiplying of HCT-116 and SF-295 cells when evaluated by the Hollow Fiber Assay (2.5 and 5mg/kg/day i.p. and 25 and 50mg/kg/day oral), with cell growth inhibition rates ranging from 33.3 to 67.4% (p<0.05). Flow cytometry experiments revealed that FC reduced membrane integrity and induced DNA fragmentation and mitochondrial depolarization (p<0.05). FC and Cas X were efficient antitumor substances against murine and human cancer cells and caused reversible morphological changes in liver, kidneys and spleens, emphasizing clerodane diterpenes as an emerging class of anticancer molecules. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. 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

  7. 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

    was not caused by impaired production of mRNA. Taken together, the study demonstrates a vitamin D-induced inhibitory effect of LPS-driven monokine production, which is most likely a vitamin D-receptor mediated phenomenon exerted at a post-transcriptional, presecretory level. Impaired monokine production may...

  8. Identification of potential anticancer compounds from Oplopanax horridus.

    Science.gov (United States)

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

    2013-08-15

    Oplopanax horridus is a plant native to North America. Previous reports have demonstrated that this herb has antiproliferative effects on cancer cells but study mostly focused on its extract or fractions. Because there has been limited phytochemical study on this herb, its bioactive compounds are largely unknown. We recently isolated and identified 13 compounds, including six polyynes, three sesquiterpenes, two steroids, and two phenolic acids, of which five are novel compounds. In this study, we systemically evaluated the anticancer effects of compounds isolated from O. horridus. Their antiproliferative effects on a panel of human colorectal and breast cancer cells were determined using the MTS assay. Cell cycle distribution and apoptotic effects were analyzed by flow cytometry. The in vivo antitumor effect was examined using a xenograft tumor model. Among the 13 compounds, strong antiproliferative effects were observed from falcarindiol and a novel compound oplopantriol A. Falcarindiol showed the most potent antiproliferative effects, significantly inducing pro-apoptosis and cell cycle arrest in the S and G2/M phases. The anticancer potential of falcarindiol was further verified in vivo, significantly inhibiting HCT-116 tumor growth in an athymic nude mouse model at 15 mg/kg. We also analyzed the relationship between polyyne structures and their pharmacological activities. We observed that both the terminal hydroxyl group and double bond obviously affected their anticancer potential. Results from this study supplied valuable information for future semi-synthesis of polyyne derivatives to develop novel cancer chemopreventive agents. Copyright © 2013 Elsevier GmbH. All rights reserved.

  9. Two likely targets for the anti-cancer effect of indole derivatives from cruciferous vegetables: PI3K/Akt/mTOR signalling pathway and the aryl hydrocarbon receptor.

    Science.gov (United States)

    Popolo, Ada; Pinto, Aldo; Daglia, Maria; Nabavi, Seyed Fazel; Farooqi, Ammad Ahmad; Rastrelli, Luca

    2017-10-01

    Diets containing high quantities of plant foods are linked with a decreased likelihood of incidence of cancer. Several common plant-based dietary components exert effects on DNA methylation levels, and can positively influence genome stability and the transcription of tumor suppressors and oncogenes. Indole-3-carbinol (I3C) is a substance present in vegetables of the Brassicaeae family, especially broccoli, white cabbage, Brussels sprouts and cauliflower. The in vivo biological effects of I3C are ascribed to a series of oligomeric products (including 3,3'-diindolylmethane), developed under acidic conditions. I3C is one of the many natural products and bioactive compounds found in foods which have recently received much attention for its potential effects in cancer prevention and treatment. In vitro studies report that I3C suppresses the proliferation of different tumor cells, including those isolated from breast, prostate, endometrium, and colon cancers. I3C resulted to be a potent in vivo chemopreventive agent for certain hormone-dependent cancers, including breast and cervical cancer. However, the mechanisms underlying these effects are not well defined. In this review, we have analysed recent literature on the use of indole derivatives against various forms of cancer, and have identified the main signalling pathways involved in their anti-cancer effect as PI3K/Akt/mTOR and the aryl hydrocarbon receptor. Copyright © 2017. Published by Elsevier Ltd.

  10. 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

  11. Ganoderma lucidum Polysaccharides as An Anti-cancer Agent.

    Science.gov (United States)

    Sohretoglu, Didem; Huang, Shile

    2017-11-13

    The mushroom Ganoderma lucidum (G. lucidum) has been used for centuries in Asian countries to treat various diseases and to promote health and longevity. Clinical studies have shown beneficial effects of G. lucidum as an alternative adjuvant therapy in cancer patients without obvious toxicity. G. lucidum polysaccharides (GLP) is the main bioactive component in the water soluble extracts of this mushroom. Evidence from in vitro and in vivo studies has demonstrated that GLP possesses potential anticancer activity through immunomodulatory, anti-proliferative, pro-apoptotic, anti-metastatic and anti-angiogenic effects. Here, we briefly summarize these anticancer effects of GLP and the underlying mechanisms. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Anticancer drugs in Portuguese surface waters - Estimation of concentrations and identification of potentially priority drugs.

    Science.gov (United States)

    Santos, Mónica S F; Franquet-Griell, Helena; Lacorte, Silvia; Madeira, Luis M; Alves, Arminda

    2017-10-01

    Anticancer drugs, used in chemotherapy, have emerged as new water contaminants due to their increasing consumption trends and poor elimination efficiency in conventional water treatment processes. As a result, anticancer drugs have been reported in surface and even drinking waters, posing the environment and human health at risk. However, the occurrence and distribution of anticancer drugs depend on the area studied and the hydrological dynamics, which determine the risk towards the environment. The main objective of the present study was to evaluate the risk of anticancer drugs in Portugal. This work includes an extensive analysis of the consumption trends of 171 anticancer drugs, sold or dispensed in Portugal between 2007 and 2015. The consumption data was processed aiming at the estimation of predicted environmental loads of anticancer drugs and 11 compounds were identified as potentially priority drugs based on an exposure-based approach (PEC b > 10 ng L -1 and/or PEC c > 1 ng L -1 ). In a national perspective, mycophenolic acid and mycophenolate mofetil are suspected to pose high risk to aquatic biota. Moderate and low risk was also associated to cyclophosphamide and bicalutamide exposition, respectively. Although no evidences of risk exist yet for the other anticancer drugs, concerns may be associated with long term effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Diversity and Transcriptional Levels of RuBisCO Form II of Sulfur-Oxidizing γ-Proteobacteria in Coastal-Upwelling Waters with Seasonal Anoxia

    Directory of Open Access Journals (Sweden)

    Bárbara Léniz

    2017-07-01

    Full Text Available Seasonal wind-driven upwelling, high primary production in surface waters, and oxygen deficiency in subsurface waters characterize the coastal ecosystem of the subtropical eastern South Pacific (ESP, and shape the nature and dynamics of the microbial community structure and function. We investigated the diversity, abundance, and transcriptional levels of the gene encoding the large subunit form II of the RuBisCO enzyme (cbbM in the pelagic microbial community at a continental-shelf site off central Chile over 2 years. We focused on cbbM genes affiliated with the sulfur-oxidizing γ-proteobacteria cluster, whose members are known to dominate in oxygen-deficient marine environments and are highly abundant in the study area. Phylogenetic analysis of cbbM sequences suggests the presence of a novel group of chemolithoautotrophs, closely related to the SUP05/ARCTIC96BD-19 clade. Through (RT-qPCR, we studied the cbbM gene abundance and transcript dynamics over an annual cycle, finding a significantly higher number of cbbM copies per unit volume in months of active upwelling and at depths in which oxygen was scarce or absent. The same temporal pattern was observed at the transcriptional level. We also analyzed the relative expression of key genes for carbon, nitrogen and sulfur cycling in six metatranscriptomic datasets, for two characteristic periods within the annual cycle: the anoxic upwelling and the suboxic downwelling. Our results indicate that coastal waters of the subtropical ESP contain transcriptionally active populations of carbon fixing pelagic bacteria, whose dynamics is controlled, in large part, by fluctuations in oxygen levels. They also suggest that chemolithoautotrophic processes coupled to the sulfur and nitrogen cycles become increasingly important for the carbon economy of marine coastal waters as oxygen concentrations decline.

  14. NaCl concentration in the medium modulates the secretion of active EmpA protease in Vibrio anguillarum at post-transcriptional level.

    Science.gov (United States)

    Crisafi, F; Denaro, R; Yakimov, M; Felice, M R; Giuliano, L; Genovese, L

    2015-12-01

    This study focused on the influence of different amounts of NaCl in the medium in Vibrio anguillarum EmpA protease production at both the transcriptional and post-transcriptional levels. Vibrio anguillarum 975/I was cultivated in cM9 medium with varying concentrations of NaCl: 0·5, 1·5, 3·0%. EmpA protease was monitored in the supernatants by the skim milk test, azocasein assay and Western blot analysis. The empA gene expression was measured by real-time PCR. A mutant strain 975/I defective for the empA gene confirmed the specificity of the response for EmpA protease. Active protease production was induced by 0·5 and 1·5% NaCl-amended media; however, the strain cultivated in 3·0% NaCl was unable to secrete EmpA protease. The quantitative expression of the empA gene was very similar in all tested conditions. The NaCl concentration in the medium modulates the secretion of active EmpA protease in V. anguillarum at a post-transcriptional level. EmpA protease is one of the most important virulence factors in V. anguillarum. We demonstrated the influence of osmotic changes in the regulation of EmpA protease in the V. anguillarum 975/I strain. This finding has an important impact on the evaluation of factors determining the onset of disease in fish. © 2015 The Society for Applied Microbiology.

  15. Nitrogen regulation of protein-protein interactions and transcript levels of GlnK PII regulator and AmtB ammonium transporter homologs in Archaea.

    Science.gov (United States)

    Pedro-Roig, Laia; Lange, Christian; Bonete, María José; Soppa, Jörg; Maupin-Furlow, Julie

    2013-10-01

    Gene homologs of GlnK PII regulators and AmtB-type ammonium transporters are often paired on prokaryotic genomes, suggesting these proteins share an ancient functional relationship. Here, we demonstrate for the first time in Archaea that GlnK associates with AmtB in membrane fractions after ammonium shock, thus, providing a further insight into GlnK-AmtB as an ancient nitrogen sensor pair. For this work, Haloferax mediterranei was advanced for study through the generation of a pyrE2-based counterselection system that was used for targeted gene deletion and expression of Flag-tagged proteins from their native promoters. AmtB1-Flag was detected in membrane fractions of cells grown on nitrate and was found to coimmunoprecipitate with GlnK after ammonium shock. Thus, in analogy to bacteria, the archaeal GlnK PII may block the AmtB1 ammonium transporter under nitrogen-rich conditions. In addition to this regulated protein-protein interaction, the archaeal amtB-glnK gene pairs were found to be highly regulated by nitrogen availability with transcript levels high under conditions of nitrogen limitation and low during nitrogen excess. While transcript levels of glnK-amtB are similarly regulated by nitrogen availability in bacteria, transcriptional regulators of the bacterial glnK promoter including activation by the two-component signal transduction proteins NtrC (GlnG, NRI) and NtrB (GlnL, NRII) and sigma factor σ(N) (σ(54) ) are not conserved in archaea suggesting a novel mechanism of transcriptional control. © 2013 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  16. Bone-remodeling transcript levels are independent of perching in end-of-lay white leghorn chickens.

    Science.gov (United States)

    Dale, Maurice D; Mortimer, Erin M; Kolli, Santharam; Achramowicz, Erik; Borchert, Glenn; Juliano, Steven A; Halkyard, Scott; Sietz, Nick; Gatto, Craig; Hester, Patricia Y; Rubin, David A

    2015-01-23

    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.

  17. 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.

  18. Anticancer Effect of a Novel Octahydropyrazino[2,1-a:5,4-a′]diisoquinoline Derivative and Its Synergistic Action with Nigella sativa in Human Gastric Cancer Cells

    Science.gov (United States)

    Czajkowska, Anna; Pawłowska, Natalia; Czarnomysy, Robert; Nazaruk, Jolanta; Szymanowski, Wojciech; Bielawska, Anna; Bielawski, Krzysztof

    2017-01-01

    Many studies have shown that naturally occurring compounds may support prevention and treatment of various diseases, including cancer. Pharmacological investigations revealed a wide spectrum of Nigella sativa biological activities. Combining natural compounds together with synthetic drugs may increase the anticancer activity and limit severe side effects of such a treatment and may be an alternative to monotherapy. The aim of the study was to evaluate the cytotoxic and proapoptotic effects of a novel octahydropyrazino[2,1-a:5,4-a′]diisoquinoline derivative and its effect in combination with Nigella sativa seed oil or extract in human gastric cancer cells (AGS). Etoposide was used as a reference. Our studies proved that combination strategy based on novel octahydropyrazino[2,1-a:5,4-a′]diisoquinoline derivative (OM-90) with Nigella sativa seed oil or extract represents the strongest efficacy in AGS cancer cells as compared to monotherapy and combined treatment with Nigella sativa seed oil or extract together with etoposide. Such a combination also leads to the activation of mitochondrial pathway, which plays a significant role in molecular mechanism of induction of apoptosis by these compounds. PMID:29441354

  19. Synthetic Methods of Quinoline Derivatives as Potent Anticancer Agents.

    Science.gov (United States)

    Sharma, Vaibhav; Mehta, Dinesh Kumar; Das, Rina

    2017-01-01

    On account of significant biological activities, quinoline derivatives have drawn more attention to the synthesis and biological activities in the search for new therapeutic agents. Several new synthetic approaches have been implemented to derive new molecules from quinoline and all the synthesized molecules showed effective anticancer activity. Some molecules are synthesized using quinolones as precursor reactant, which is another effective product of quinoline, also showing significant activity against malignant tumors. The presence of nitrogen in it and its ability to bind with enzymes like gyrase, topoisomerase II and kinase have also proven it with antitumor activity. This review encapsulates the recent advances in the synthesis and anticancer activity of Quinoline derivatives. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Glycolysis Inhibitors for Anticancer Therapy: A Review of Recent Patents.

    Science.gov (United States)

    Sheng, Huaming; Tang, Weijuan

    2016-01-01

    The aerobic glycolysis in tumor cells known as Warburg effect is one of the most important hallmarks of cancer. It is proposed that the upregulation of the series of metabolic enzymes along the glycolytic pathway may contribute to the Warburg effect. The inhibition of these glycolytic enzymes has been found to be a novel strategy for anticancer treatment. This review summaries recent patents in the development of small molecule inhibitors for the key enzymes in tumor glycolysis. The targeted enzymes are GLUTs, HKs, PFK, PGAM1, PKM2, LDHA, MCTs and PDK. Although most inhibitors are still in the preclinical phase, the inhibition of glycolytic enzymes represents a very promising approach for anticancer treatment. The future development could be more focused on the discovery of new metabolic enzyme that is specifically expressed in tumor cells.

  1. Molecular targets and anti-cancer potential of escin.

    Science.gov (United States)

    Cheong, Dorothy H J; Arfuso, Frank; Sethi, Gautam; Wang, Lingzhi; Hui, Kam Man; Kumar, Alan Prem; Tran, Thai

    2018-02-21

    Escin is a mixture of triterpenoid saponins extracted from the horse chestnut tree, Aesculus hippocastanum. Its potent anti-inflammatory and anti-odematous properties makes it a choice of therapy against chronic venous insufficiency and odema. More recently, escin is being actively investigated for its potential activity against diverse cancers. It exhibits anti-cancer effects in many cancer cell models including lung adenocarcinoma, hepatocellular carcinoma and leukemia. Escin also attenuates tumor growth and metastases in various in vivo models. Importantly, escin augments the effects of existing chemotherapeutic drugs, thereby supporting the role of escin as an adjunct or alternative anti-cancer therapy. The beneficial effects of escin can be attributed to its inhibition of proliferation and induction of cell cycle arrest. By regulating transcription factors/growth factors mediated oncogenic pathways, escin also potentially mitigates chronic inflammatory processes that are linked to cancer survival and resistance. This review provides a comprehensive overview of the current knowledge of escin and its potential as an anti-cancer therapy through its anti-proliferative, pro-apoptotic, and anti-inflammatory effects. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Phytochemical, Anticancer and Antioxidant Evaluation of Potential ...

    African Journals Online (AJOL)

    BSN

    Key words: anticancer, antioxidant, C. surinamensis, phytochemical investigation, plant extract ... agents active against cancer and infectious diseases ..... (2004). Wine polyphenols and ethanol do not significantly scavenge superoxide nor affect endothelial nitric oxide production. Journal of. Nutritional. Biochemistry.

  3. 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.

  4. 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.

  5. Anticancer Activity of Toxins from Bee and Snake Venom—An Overview on Ovarian Cancer

    OpenAIRE

    Marius Alexandru Moga; Oana Gabriela Dimienescu; Cristian Andrei Arvătescu; Petru Ifteni; Liana Pleş

    2018-01-01

    Cancer represents the disease of the millennium, a major problem in public health. The proliferation of tumor cells, angiogenesis, and the relationship between the cancer cells and the components of the extracellular matrix are important in the events of carcinogenesis, and these pathways are being used as targets for new anticancer treatments. Various venoms and their toxins have shown possible anticancer effects on human cancer cell lines, providing new perspectives in drug development. In ...

  6. Anti-cancer activities of Ganoderma lucidum: active ingredients and pathways

    OpenAIRE

    Chi H.J. Kao; Amalini C. Jesuthasan; Karen S. Bishop; Marcus P. Glucina; Lynnette R. Ferguson

    2013-01-01

    ABSTRACTGanoderma lucidum, commonly referred to as Lingzhi, has been used in Asia for health promotion for centuries. The anti-cancer effects of G. lucidum have been demonstrated in both in vitro and in vivo studies. In addition, the observed anti-cancer activities of Ganoderma have prompted its usage by cancer patients alongside chemotherapy.The main two bioactive components of G. lucidum can be broadly grouped into triterpenes and polysaccharides. Despite triterpenes and polysaccharides bei...

  7. Synergistic Anticancer Action of Lysosomal Membrane Permeabilization and Glycolysis Inhibition.

    Science.gov (United States)

    Kosic, Milica; Arsikin-Csordas, Katarina; Paunovic, Verica; Firestone, Raymond A; Ristic, Biljana; Mircic, Aleksandar; Petricevic, Sasa; Bosnjak, Mihajlo; Zogovic, Nevena; Mandic, Milos; Bumbasirevic, Vladimir; Trajkovic, Vladimir; Harhaji-Trajkovic, Ljubica

    2016-10-28

    We investigated the in vitro and in vivo anticancer effect of combining lysosomal membrane permeabilization (LMP)-inducing agent N-dodecylimidazole (NDI) with glycolytic inhibitor 2-deoxy-d-glucose (2DG). NDI-triggered LMP and 2DG-mediated glycolysis block synergized in inducing rapid ATP depletion, mitochondrial damage, and reactive oxygen species production, eventually leading to necrotic death of U251 glioma cells but not primary astrocytes. NDI/2DG-induced death of glioma cells was partly prevented by lysosomal cathepsin inhibitor E64 and antioxidant α-tocopherol, suggesting the involvement of LMP and oxidative stress in the observed cytotoxicity. LMP-inducing agent chloroquine also displayed a synergistic anticancer effect with 2DG, whereas glucose deprivation or glycolytic inhibitors iodoacetate and sodium fluoride synergistically cooperated with NDI, thus further indicating that the anticancer effect of NDI/2DG combination was indeed due to LMP and glycolysis block. The two agents synergistically induced ATP depletion, mitochondrial depolarization, oxidative stress, and necrotic death also in B16 mouse melanoma cells. Moreover, the combined oral administration of NDI and 2DG reduced in vivo melanoma growth in C57BL/6 mice by inducing necrotic death of tumor cells, without causing liver, spleen, or kidney toxicity. Based on these results, we propose that NDI-triggered LMP causes initial mitochondrial damage that is further increased by 2DG due to the lack of glycolytic ATP required to maintain mitochondrial health. This leads to a positive feedback cycle of mitochondrial dysfunction, ATP loss, and reactive oxygen species production, culminating in necrotic cell death. Therefore, the combination of LMP-inducing agents and glycolysis inhibitors seems worthy of further exploration as an anticancer strategy. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Resveratrol as an anti-cancer agent: A review.

    Science.gov (United States)

    Rauf, Abdur; Imran, Muhammad; Butt, Masood Sadiq; Nadeem, Muhammad; Peters, Dennis G; Mubarak, Mohammad S

    2016-12-21

    Owing to their antimicrobial, antioxidant, and anti-inflammatory activity, grapes (Vitis vinifera L.) are the archetypal paradigms of fruits used not only for nutritional purposes, but also for exclusive therapeutics. Grapes are a prominent and promising source of phytochemicals, especially resveratrol, a phytoalexin antioxidant found in red grapes which has both chemopreventive and therapeutic effects against various ailments. Resveratrol's role in reducing different human cancers, including breast, cervical, uterine, blood, kidney, liver, eye, bladder, thyroid, esophageal, prostate, brain, lung, skin, gastric, colon, head and neck, bone, ovarian, and cervical, has been reviewed. This review covers the literature that deals with the anti-cancer mechanism of resveratrol with special reference to antioxidant potential. Furthermore, this article summarizes the literature pertaining to resveratrol as an anti-cancer agent.

  9. 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.

  10. Potential Anticancer Properties of Grape Antioxidants

    Directory of Open Access Journals (Sweden)

    Kequan Zhou

    2012-01-01

    Full Text Available Dietary intake of foods rich in antioxidant properties is suggested to be cancer protective. Foods rich in antioxidant properties include grape (Vitis vinifera, one of the world’s largest fruit crops and most commonly consumed fruits in the world. The composition and cancer-protective effects of major phenolic antioxidants in grape skin and seed extracts are discussed in this review. Grape skin and seed extracts exert strong free radical scavenging and chelating activities and inhibit lipid oxidation in various food and cell models in vitro. The use of grape antioxidants are promising against a broad range of cancer cells by targeting epidermal growth factor receptor (EGFR and its downstream pathways, inhibiting over-expression of COX-2 and prostaglandin E2 receptors, or modifying estrogen receptor pathways, resulting in cell cycle arrest and apoptosis. Interestingly, some of these activities were also demonstrated in animal models. However, in vivo studies have demonstrated inconsistent antioxidant efficacy. Nonetheless, a growing body of evidence from human clinical trials has demonstrated that consumption of grape, wine and grape juice exerts many health-promoting and possible anti-cancer effects. Thus, grape skin and seed extracts have great potential in cancer prevention and further investigation into this exciting field is warranted.

  11. CNS Anticancer Drug Discovery and Development: 2016 conference insights.

    Science.gov (United States)

    Levin, Victor A; Abrey, Lauren E; Heffron, Timothy P; Tonge, Peter J; Dar, Arvin C; Weiss, William A; Gallo, James M

    2017-07-18

    CNS Anticancer Drug Discovery and Development November 2016, AZ, USA The 2016 second CNS Anticancer Drug Discovery and Development Conference addressed diverse viewpoints about why new drug discovery/development focused on CNS cancers has been sorely lacking. Despite more than 70,000 individuals in the USA being diagnosed with a primary brain malignancy and 151,669-286,486 suffering from metastatic CNS cancer, in 1999, temozolomide was the last drug approved by the US FDA as an anticancer agent for high-grade gliomas. Among the topics discussed were economic factors and pharmaceutical risk assessments, regulatory constraints and perceptions and the need for improved imaging surrogates of drug activity. Included were modeling tumor growth and drug effects in a medical environment in which direct tumor sampling for biological effects can be problematic, potential new drugs under investigation and targets for drug discovery and development. The long trajectory and diverse impediments to novel drug discovery, and expectation that more than one drug will be needed to adequately inhibit critical intracellular tumor pathways were viewed as major disincentives for most pharmaceutical/biotechnology companies. While there were a few unanimities, one consensus is the need for continued and focused discussion among academic and industry scientists and clinicians to address tumor targets, new drug chemistry, and more time- and cost-efficient clinical trials based on surrogate end points.

  12. Low-shear-modeled microgravity-grown Penicillium chrysogenum-mediated biosynthesis of silver nanoparticles with enhanced antimicrobial activity and its anticancer effect in human liver cancer and fibroblast cells.

    Science.gov (United States)

    Sheet, Sunirmal; Sathishkumar, Yesupatham; Sivakumar, Allur Subramaniyam; Shim, Kwan Seob; Lee, Yang Soo

    2017-10-01

    Gravitational force and shear forces induce various changes in gene expression and metabolite production of microorganisms. Previous reports have shown that there are differences in the expression of different sets of proteins and enzymes under microgravity conditions compared to normal gravity. The aim of this study is to utilize culture filtrates of Penicillium chrysogenum grown under microgravity and normal conditions to synthesize silver nanoparticles and to examine whether there is any difference between their physiochemical and biological function. Synthesized nanoparticles were characterized using UV-Vis spectroscopy, FTIR, XRD, and TEM. Biological functional studies such as antimicrobial activity, cytotoxic studies, and anticancer activity were carried out. Antimicrobial activity was tested using antibiotic susceptibility testing by Kirby-Bauer method and cytotoxicity tests were carried out using 3T3-L1 normal fibroblasts cells and Hep-G2 cancer cell lines. Interestingly, our results indicated that microgravity-synthesized silver nanoparticles possess enhanced antibacterial activity and cytotoxic effect against cancer cells compared to normal gravity-synthesized silver nanoparticle. This work highlighted the importance of gravitational vector on the fungal enzyme profiles and their role in silver nanoparticle synthesis with enhanced biological activity.

  13. 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. © 2016 S. Karger AG, Basel.

  14. 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.

  15. Anticancer activity of selected Colocasia gigantia fractions.

    Science.gov (United States)

    Pornprasertpol, Apichai; Sereemaspun, Amornpun; Sooklert, Kanidta; Satirapipatkul, Chutimon; Sukrong, Suchada

    2015-01-01

    The objective of this study is to investigate the anticancer potential of the extract of Colocasia gigantea C. gigantea), a plant member of the Araceae family. In the present study, we investigated the cytotoxic activity of C. gigantea extract on cervical cancer (Hela) and human white blood cells (WBC) in vitro. The authors then identified the bioactive ingredients that demonstrated cytotoxicity on tested cells and evaluated those bioactive ingredients using the bioassay-guided fractionation method. The results showed that not all parts of C. gigantea promote cytotoxic activity. The dichloromethane leaf fraction showed significant cell proliferation effect on Hela cells, but not on WBCs. Only the n-hexane tuber fraction (Fr. 1T) exhibited significant cytotoxicity on Hela cells (IC50 = 585 μg/ml) and encouraged WBC cell proliferation. From GC-Mass spectrometry, 4,22-Stigmastadiene-3-one, Diazoprogesterone, 9-Octadecenoic acid (Z)-, hexyl ester and Oleic Acid were the components of Fr 1T that demonstrated cytotoxic potential. In conclusion, C. gigantea's Fr 1T shows potential for cervical cancer treatment.

  16. 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.

  17. Marine Sponge Natural Products with Anticancer Potential: An Updated Review.

    Science.gov (United States)

    Calcabrini, Cinzia; Catanzaro, Elena; Bishayee, Anupam; Turrini, Eleonora; Fimognari, Carmela

    2017-10-13

    Despite the huge investment into research and the significant effort and advances made in the search for new anticancer drugs in recent decades, cancer cure and treatment continue to be a formidable challenge. Many sources, including plants, animals, and minerals, have been explored in the oncological field because of the possibility of identifying novel molecular therapeutics. Marine sponges are a prolific source of secondary metabolites, a number of which showed intriguing tumor chemopreventive and chemotherapeutic properties. Recently, Food and Drug Administration-approved drugs derived from marine sponges have been shown to reduce metastatic breast cancer, malignant lymphoma, and Hodgkin's disease. The chemopreventive and potential anticancer activity of marine sponge-derived compounds could be explained by multiple cellular and molecular mechanisms, including DNA protection, cell-cycle modulation, apoptosis, and anti-inflammatory activities as well as their ability to chemosensitize cancer cells to traditional antiblastic chemotherapy. The present article aims to depict the multiple mechanisms involved in the chemopreventive and therapeutic effects of marine sponges and critically explore the limitations and challenges associated with the development of marine sponge-based anticancer strategy.

  18. Changes in transcript levels of starch hydrolysis genes and raising citric acid production via carbon ion irradiation mutagenesis of Aspergillus niger.

    Science.gov (United States)

    Hu, Wei; Li, Wenjian; Chen, Hao; Liu, Jing; Wang, Shuyang; Chen, Jihong

    2017-01-01

    The filamentous ascomycete Aspergillus niger is well known for its ability to accumulate citric acid for the hydrolysis of starchy materials. To improve citric acid productivity, heavy ion beam mutagenesis was utilized to produce mutant A.niger strains with enhanced production of citric acid in this work. It was demonstrated that a mutant HW2 with high concentration of citric acid was isolated after carbon ion irradiation with the energy of 80Mev/μ, which was obvious increase higher than the original strain from liquefied corn starch as a feedstock. More importantly, with the evidence from the expression profiles of key genes and enzyme activity involved in the starch hydrolysis process between original strain and various phenotype mutants, our results confirmed that different transcript levels of key genes involving in starch hydrolysis process between original strain and mutants could be a significant contributor to different citric acid concentration in A.niger, such as, amyR and glaA, which therefore opened a new avenue for constructing genetically engineered A.niger mutants for high-yield citric acid accumulation in the future. As such, this work demonstrated that heavy ion beam mutagenesis presented an efficient alternative strategy to be developed to generate various phenotype microbe species mutants for functional genes research.

  19. Cadmium down-regulates expression of XIAP at the post-transcriptional level in prostate cancer cells through an NF-κB-independent, proteasome-mediated mechanism

    Directory of Open Access Journals (Sweden)

    Fox Eric

    2010-07-01

    Full Text Available Abstract Background Cadmium has been classified as a human carcinogen, affecting health through occupational and environmental exposure. Cadmium has a long biological half-life (>25 years, due to the flat kinetics of its excretion. The prostate is one of the organs with highest levels of cadmium accumulation. Importantly, patients with prostate cancer appear to have higher levels of cadmium both in the circulation and in prostatic tissues. Results In the current report, we demonstrate for the first time that cadmium down-regulates expression of the X-linked inhibitor of apoptosis protein (XIAP in prostate cancer cells. Cadmium-mediated XIAP depletion occurs at the post-transcriptional level via an NF-κB-independent, proteasome-mediated mechanism and coincides with an increased sensitivity of prostate cancer cells to TNF-α-mediated apoptosis. Prolonged treatment with cadmium results in selection of prostate cancer cells with apoptosis-resistant phenotype. Development of apoptosis-resistance coincides with restoration of XIAP expression in cadmium-selected PC-3 cells. Conclusions Selection of cadmium-resistant cells could represent an adaptive survival mechanism that may contribute to progression of prostatic malignancies.

  20. 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.

  1. Changes in transcript levels of starch hydrolysis genes and raising citric acid production via carbon ion irradiation mutagenesis of Aspergillus niger.

    Directory of Open Access Journals (Sweden)

    Wei Hu

    Full Text Available The filamentous ascomycete Aspergillus niger is well known for its ability to accumulate citric acid for the hydrolysis of starchy materials. To improve citric acid productivity, heavy ion beam mutagenesis was utilized to produce mutant A.niger strains with enhanced production of citric acid in this work. It was demonstrated that a mutant HW2 with high concentration of citric acid was isolated after carbon ion irradiation with the energy of 80Mev/μ, which was obvious increase higher than the original strain from liquefied corn starch as a feedstock. More importantly, with the evidence from the expression profiles of key genes and enzyme activity involved in the starch hydrolysis process between original strain and various phenotype mutants, our results confirmed that different transcript levels of key genes involving in starch hydrolysis process between original strain and mutants could be a significant contributor to different citric acid concentration in A.niger, such as, amyR and glaA, which therefore opened a new avenue for constructing genetically engineered A.niger mutants for high-yield citric acid accumulation in the future. As such, this work demonstrated that heavy ion beam mutagenesis presented an efficient alternative strategy to be developed to generate various phenotype microbe species mutants for functional genes research.

  2. Changes in transcript levels of starch hydrolysis genes and raising citric acid production via carbon ion irradiation mutagenesis of Aspergillus niger

    Science.gov (United States)

    Li, Wenjian; Chen, Hao; Liu, Jing; Wang, Shuyang; Chen, Jihong

    2017-01-01

    The filamentous ascomycete Aspergillus niger is well known for its ability to accumulate citric acid for the hydrolysis of starchy materials. To improve citric acid productivity, heavy ion beam mutagenesis was utilized to produce mutant A.niger strains with enhanced production of citric acid in this work. It was demonstrated that a mutant HW2 with high concentration of citric acid was isolated after carbon ion irradiation with the energy of 80Mev/μ, which was obvious increase higher than the original strain from liquefied corn starch as a feedstock. More importantly, with the evidence from the expression profiles of key genes and enzyme activity involved in the starch hydrolysis process between original strain and various phenotype mutants, our results confirmed that different transcript levels of key genes involving in starch hydrolysis process between original strain and mutants could be a significant contributor to different citric acid concentration in A.niger, such as, amyR and glaA, which therefore opened a new avenue for constructing genetically engineered A.niger mutants for high-yield citric acid accumulation in the future. As such, this work demonstrated that heavy ion beam mutagenesis presented an efficient alternative strategy to be developed to generate various phenotype microbe species mutants for functional genes research. PMID:28650980

  3. 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.

  4. 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.

  5. 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.

  6. Solvent/co-solvent effects on the electronic properties and adsorption mechanism of anticancer drug Thioguanine on Graphene oxide surface as a nanocarrier: Density functional theory investigation and a molecular dynamics

    Science.gov (United States)

    Hasanzade, Zohre; Raissi, Heidar

    2017-11-01

    In this work, the adsorption of Thioguanine (TG) anticancer drug on the surface of Graphene oxide (GO) nanosheet has investigated using density functional theory (DFT) and molecular dynamics simulation (MDs). Quantum mechanics calculations by two methods including M06-2X/6-31G**and ωB97X-D/6-31G** have been employed to calculate the details of energetic, geometric, and electronic properties of the TG molecule interacting with Graphene oxide nanosheet (GONS). DFT calculations confirmed that the strongest adsorption is observed when hydrogen bond interactions between TG molecule and the functional groups of Graphene oxide nanosheet are predominate. In all calculations, solvent effects have been considered in water using the PCM method. It is found that TG molecule can be adsorbed on Graphene oxide with negative solvation energy, indicating the TG adsorption on Graphene oxide surfaces is thermodynamically favored. Moreover, MD simulations are examined to understand the solvent/co-solvent effect (water, ethanol, nicotine) on the Thioguanine drug delivery through Graphene oxide. The results of RDF patterns and the van der Waals energy calculations show that interaction between TG drugs and the Graphene oxide surface is stronger in water solvent compared to the other co-solvent. The obtained MD results illustrate that when nicotine and ethanol exist in the system, the drug takes longer time to bind with GO nanosheet and the system becomes unstable. It can be concluded that Graphene oxide can be a promising candidate in water media for delivery the TG molecule.

  7. The Influence of Developmental Stage on the Relationship Between Severity of Late Effects of Anticancer Therapy and Perceived Quality of Life of Childhood Cancer Survivors

    Czech Academy of Sciences Publication Activity Database

    Blatný, Marek; Jelínek, Martin; Sobotková, Veronika; Kepák, T.

    2013-01-01

    Roč. 3, August (2013), s. 1-5 ISSN 2158-2440 R&D Projects: GA ČR(CZ) GAP407/11/2421 Institutional support: RVO:68081740 Keywords : childhood cancer survivors * quality of life * late effects * age differences Subject RIV: AN - Psychology http://sgo.sagepub.com/content/3/3/2158244013500678

  8. Magnetic polymer nanospheres for anticancer drug targeting

    International Nuclear Information System (INIS)

    JurIkova, A; Csach, K; Koneracka, M; Zavisova, V; Tomasovicova, N; Lancz, G; Kopcansky, P; Timko, M; Miskuf, J; Muckova, M

    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.

  9. Anti-cancer effect of bee venom in prostate cancer cells through activation of caspase pathway via inactivation of NF-κB.

    Science.gov (United States)

    Park, Mi Hee; Choi, Myoung Suk; Kwak, Dong Hoon; Oh, Ki-Wan; Yoon, Do Young; Han, Sang Bae; Song, Ho Sueb; Song, Min Jong; Hong, Jin Tae

    2011-06-01

    Bee venom has been used as a traditional medicine to treat arthritis, rheumatism, back pain, cancerous tumors, and skin diseases. However, the effects of bee venom on the prostate cancer and their action mechanisms have not been reported yet. To determine the effect of bee venom and its major component, melittin on the prostate cancer cells, apoptosis is analyzed by tunnel assay and apoptotic gene expression. For xenograft studies, bee venom was administrated intraperitoneally twice per week for 4 weeks, and the tumor growth was measured and the tumor were analyzed by immunohistochemistry. To investigate whether bee venom and melittin can inactivate nuclear factor kappa B (NF-κB), we assessed NF-κB activity in vitro and in vivo. Bee venom (1-10 µg/ml) and melittin (0.5-2.5 µg/ml) inhibited cancer cell growth through induction of apoptotic cell death in LNCaP, DU145, and PC-3 human prostate cancer cells. These effects were mediated by the suppression of constitutively activated NF-κB. Bee venom and melittin decreased anti-apoptotic proteins but induced pro-apoptotic proteins. However, pan caspase inhibitor abolished bee venom and melittin-induced apoptotic cell death and NF-κB inactivation. Bee venom (3-6 mg/kg) administration to nude mice implanted with PC-3 cells resulted in inhibition of tumor growth and activity of NF-κB accompanied with apoptotic cell death. Therefore, these results indicated that bee venom and melittin could inhibit prostate cancer in in vitro and in vivo, and these effects may be related to NF-κB/caspase signal mediated induction of apoptotic cell death. Copyright © 2010 Wiley-Liss, Inc.

  10. Synthesis and Biological Evaluation of Isomeric Methoxy Substitutions on Anti-Cancer Indolyl-Pyridinyl-Propenones: Effects on Potency and Mode of Activity

    OpenAIRE

    Trabbic, Christopher J.; George, Sage M.; Alexander, Evan M.; Du, Shengnan; Offenbacher, Jennifer M.; Crissman, Emily J.; Overmeyer, Jean H.; Maltese, William A.; Erhardt, Paul W.

    2016-01-01

    Certain indolyl-pyridinyl-propenone analogues kill glioblastoma cells that have become resistant to conventional therapeutic drugs. Some of these analogues induce a novel form of non-apoptotic cell death called methuosis, while others primarily cause microtubule disruption. Ready access to 5-indole substitution has allowed characterization of this position to be important for both types of mechanisms when a simple methoxy group is present. We now report the syntheses and biological effects of...

  11. Anti-cancer effect of oncolytic adenovirus-armed shRNA targeting MYCN gene on doxorubicin-resistant neuroblastoma cells.

    Science.gov (United States)

    Li, Yuan; Zhuo, Baobiao; Yin, Yiyu; Han, Tao; Li, Shixian; Li, Zhengwei; Wang, Jian

    2017-09-09

    Chemotherapy is one of the few effective choices for patients with neuroblastoma. However, the development of muti-drug resistance (MDR) to chemotherapy is a major obstacle to the effective treatment of advanced or recurrent neuroblastoma. The muti-drug resistance-associated protein (MRP), which encodes a transmembrane glycoprotein, is a key regulator of MDR. The expression of MRP is a close correlation with MYCN oncogene in neuroblastoma. We have recently shown ZD55-shMYCN (oncolytic virus armed with shRNA against MYCN) can down-regulate MYCN to inhibit tumor cells proliferation and induce apoptosis in neuroblastoma. Here we further report ZD55-shMYCN re-sensitized doxorubicin-resistant cells to doxorubicin (as shown by reduced proliferation, increased apoptosis, and inhibited cell migration), and reduced the in vivo growth rate of neuroblastoma xenografts by down-regulation of MRP expression. Sequential therapy with doxorubicin did not affect the replication of ZD55-shMYCN in doxorubicin-resistant neuroblastoma cells, but decreased the expression of Bcl-2, Bcl-X L , MMP-1. Thus, this synergistic effect of ZD55-shMYCN in combination with doxorubicin provides a novel therapy strategy for doxorubicin-resistant neuroblastoma, and is a promising approach for further clinical development. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. 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.

  13. The NF-kappa B inhibitor, celastrol, could enhance the anti-cancer effect of gambogic acid on oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    He, Di; Chen, Wantao; Xu, Qin; Yan, Ming; Zhang, Ping; Zhou, Xiaojian; Zhang, Zhiyuan; Duan, Wenhu; Zhong, Laiping; Ye, Dongxia

    2009-01-01

    Gambogic acid (GA) is a major active ingredient of gamboge, a widely used traditional Chinese medicine that has been reported to be a potent cytotoxic agent against some malignant tumors. Many studies have shown that the NF-kappa B signaling pathway plays an important role in anti-apoptosis and the drug resistance of tumor cells during chemotherapy. In this study, the effects and mechanisms of GA and the NF-kappa B inhibitor celastrol on oral cancer cells were investigated. Three human oral squamous cell carcinoma cell lines, Tca8113, TSCC and NT, were treated with GA alone, celastrol alone or GA plus celastrol. Cytotoxicity was assessed by MTT assay. The rate of apoptosis was examined with annexin V/PI staining as well as transmission electronic microscopy in Tca8113 cells. The level of constitutive NF-kappa B activity in oral squamous cell carcinoma cell lines was determined by immunofluorescence assays and nuclear extracts and electrophoretic mobility shift assays (EMSAs) in vitro. To further investigate the role of NF-kappa B activity in GA and celastrol treatment in oral squamous cell carcinoma, we used the dominant negative mutant SR-IκBα to inhibit NF-kappa B activity and to observe its influence on the effect of GA. The results showed that GA could inhibit the proliferation and induce the apoptosis of the oral squamous cell carcinoma cell lines and that the NF-kappa B pathway was simultaneously activated by GA treatment. The minimal cytotoxic dose of celastrol was able to effectively suppress the GA-induced NF-kappa B pathway activation. Following the combined treatment with GA and the minimal cytotoxic dose of celastrol or the dominant negative mutant SR-IκBα, proliferation was significantly inhibited, and the apoptotic rate of Tca8113 cells was significantly increased. The combination of GA and celastrol has a synergistic antitumor effect. The effect can be primarily attributed to apoptosis induced by a decrease in NF-kappa B pathway activation. The

  14. 10 Gallium Complexes as Anticancer Drugs.

    Science.gov (United States)

    Chitambar, Christopher R

    2018-02-05

    Clinical trials have shown gallium nitrate, a group 13 (formerly IIIa) metal salt, to have antineoplastic activity against non-Hodgkin's lymphoma and urothelial cancers. Interest in gallium as a metal with anticancer properties emerged when it was discovered that 67Ga(III) citrate injected in tumor-bearing animals localized to sites of tumor. Animal studies showed non-radioactive gallium nitrate to inhibit the growth of implanted solid tumors. Following further evaluation of its efficacy and toxicity in animals, gallium nitrate, Ga(NO3)3, was designated an investigational drug by the National Cancer Institute (USA) and advanced to Phase 1 and 2 clinical trials. Gallium(III) shares certain chemical characteristics with iron(III) which enable it to interact with iron-binding proteins and disrupt iron-dependent tumor cell growth. Gallium's mechanisms of action include the inhibition of cellular iron uptake and disruption of intracellular iron homeostasis, these effects result in inhibition of ribonucleotide reductase and mitochondrial function, and changes in the expression in proteins of iron transport and storage. Whereas the growth-inhibitory effects of gallium become apparent after 24 to 48 hours of incubation of cells, an increase in intracellular reactive oxygen species (ROS) is seen with 1 to 4 hours of incubation. Gallium-induced ROS consequently triggers the upregulation of metallothionein and hemoxygenase-1 genes. Beyond the first generation of gallium salts such as gallium nitrate and gallium chloride, a new generation of gallium-ligand complexes such as tris(8-quinolinolato)gallium(III) (KP46) and gallium maltolate has emerged. These agents are being evaluated in the clinic while other ligands for gallium are in preclinical development. These newer agents appear to possess greater antitumor efficacy and a broader spectrum of antineoplastic activity than the earlier generation of gallium compounds.

  15. 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.

  16. 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.

  17. Pharmacokinetics and absorption of the anticancer agents dasatinib and GDC-0941 under various gastric conditions in dogs--reversing the effect of elevated gastric pH with betaine HCl.

    Science.gov (United States)

    Pang, Jodie; Dalziel, Gena; Dean, Brian; Ware, Joseph A; Salphati, Laurent

    2013-11-04

    Changes in gastric pH can impact the dissolution and absorption of compounds presenting pH-dependent solubility. We assessed, in dogs, the effects of gastric pH-modifying agents on the oral absorption of two weakly basic anticancer drugs, dasatinib and GDC-0941. We also tested whether drug-induced hypochlorhydria could be temporarily mitigated using betaine HCl. Pretreatments with pentagastrin, famotidine, betaine HCl, or combinations of famotidine and betaine HCl were administered orally to dogs prior to drug dosing. The gastric pH was measured under each condition for up to 7 h, and the exposure of the compounds tested was calculated. The average gastric pH in fasted dogs ranged from 1.45 to 3.03. Pentagastrin or betaine HCl treatments lowered the pH and reduced its variability between dogs compared to control animals. In contrast, famotidine treatment maintained gastric pH at values close to 7 for up to 5 h, while betaine HCl transiently reduced the pH to approximately 2 in the famotidine-treated dogs. Famotidine pretreatment lowered GDC-0941 exposure by 5-fold, and decreased dasatinib measurable concentrations 30-fold, compared to the pentagastrin-treated dogs. Betaine HCl restored GDC-0941 AUC in famotidine-treated dogs to levels achieved in control animals, and increased dasatinib AUC to 1.5-fold that measured in control dogs. The results confirmed the negative impact of acid-reducing agents on the absorption of weakly basic drugs. They also suggested that betaine HCl coadministration may be a viable strategy in humans treated with acid-reducing agents in order to temporarily reduce gastric pH and restore drug exposure.

  18. Exploring the Effect of Polypyridyl Ligands on the Anticancer Activity of Phosphorescent Iridium(III) Complexes: From Proteosynthesis Inhibitors to Photodynamic Therapy Agents.

    Science.gov (United States)

    Pracharova, Jitka; Vigueras, Gloria; Novohradsky, Vojtech; Cutillas, Natalia; Janiak, Christoph; Kostrhunova, Hana; Kasparkova, Jana; Ruiz, José; Brabec, Viktor

    2018-03-26

    A series of five kinetically inert bis-cyclometalated Ir III complexes of general formula [Ir(C^N) 2 (N^N)][PF 6 ] [C^N=2-phenyl-1-[4-(trifluoromethyl)benzyl]-1H-benzo[d]imidazol-κN,C; N^N=1,10-phenanthroline (phen, 1), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq, 2), dipyrido[3,2-a:2',3'-c]phenazine (dppz, 3), benzo[i]dipyrido[3,2-a:2',3'-c]phenazine (dppn, 4), and dipyrido[3,2-a:2',3'-c]phenazine-10,11-imidazolone (dppz-izdo, 5)] were designed and synthesized to explore the effect of the degree of π conjugation of the polypyridyl ligand on their toxicity in cancer cells. We show that less-lipophilic complexes 1 and 2 exhibit the highest toxicity [sub-micromolar inhibitory concentration (IC 50 ) values] in A2780, HeLa, and MCF-7 cancer cells, and they are markedly more efficient than clinically used platinum drugs. It is noteworthy that the investigated Ir agents display the capability to overcome acquired and inherent resistance to conventional cisplatin (in A2780cisR and MCF-7 cells, respectively). We demonstrate that the Ir complexes, unlike clinically used platinum antitumor drugs, do not kill cells through DNA-damage response. Rather, they kill cells by inhibiting protein translation by targeting preferentially the endoplasmic reticulum. Our findings also reveal that the toxic effect of the Ir complexes can be significantly potentiated by irradiation with visible light (by more than two orders of magnitude). The photopotentiation of the investigated Ir complexes can be attributed to a marked increase (≈10-30-fold) in intracellular reactive oxygen species. Collectively, these data highlight the functional diversity of antitumor metal-based drugs and the usefulness of a mechanism-based rationale for selecting candidate agents that are effective against chemoresistant tumors for further preclinical testing. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Good fashion is evolution, not revolution" - methods to enhance existing anticancer medicines, primarily with use of transition metal.

    Science.gov (United States)

    Guzowska, Magdalena Katarzyna; Kalinowska, Monika; Lewandowski, Wlodzimierz

    2017-11-29

    The constant search for a successful cancer therapies lasts for decades. Apart from the huge scientific effort and enormous sum of spent money, only a small amount of newly developed medicines move into clinical use (only 94 registered anticancer drugs in the last 12 years [1]). Anticancer regimes are still overcome by drugs invented over 50 years ago such as cisplatin and doxorubicin. Significant progress in the development of improved anticancer drugs was made due to multiple studies on the relationship between the molecular structure of chemical compounds and their cytostatic activity. A number of ligands (mainly organic) with quite effective anticancer properties are known, but they show insufficient activity, selectivity and multidrug resistance. Formation of transition metal - ligand complexes (with proven anticancer effect) changes the properties of the latter. The factors that affect the cytotoxic properties of metal complexes are: the type of ligand and metal, the nature of the connection between metal and ligand, and the distribution of electronic charge density in the formed complexes. Here, we report the recent efforts to improve existing compounds with confirmed anticancer activity. They seem to be unappreciated as their effects appear to be less spectacular than that of targeted anticancer drugs (i.e. based on antibodies or small RNAs). Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Anti-cancer effect of bee venom on colon cancer cell growth by activation of death receptors and inhibition of nuclear factor kappa B.

    Science.gov (United States)

    Zheng, Jie; Lee, Hye Lim; Ham, Young Wan; Song, Ho Sueb; Song, Min Jong; Hong, Jin Tae

    2015-12-29

    Bee venom (BV) has been used as a traditional medicine to treat arthritis, rheumatism, back pain, cancerous tumors, and skin diseases. However, the effects of BV on the colon cancer and their action mechanisms have not been reported yet. We used cell viability assay and soft agar colony formation assay for testing cell viability, electro mobility shift assay for detecting DNA binding activity of nuclear factor kappa B (NF-κB) and Western blotting assay for detection of apoptosis regulatory proteins. We found that BV inhibited growth of colon cancer cells through induction of apoptosis. We also found that the expression of death receptor (DR) 4, DR5, p53, p21, Bax, cleaved caspase-3, cleaved caspase-8, and cleaved caspase-9 was increased by BV treatment in a dose dependent manner (0-5 μg/ml). Consistent with cancer cell growth inhibition, the DNA binding activity of nuclear factor kappa B (NF-κB) was also inhibited by BV treatment. Besides, we found that BV blocked NF-κB activation by directly binding to NF-κB p50 subunit. Moreover, combination treatment with BV and p50 siRNA or NF-κB inhibitor augmented BV-induced cell growth inhibition. However, p50 mutant plasmid (C62S) transfection partially abolished BV-induced cell growth inhibiton. In addition, BV significantly suppressed tumor growth in vivo. Therefore, these results suggested that BV could inhibit colon cancer cell growth, and these anti-proliferative effects may be related to the induction of apoptosis by activation of DR4 and DR5 and inhibition of NF-κB.

  1. 17β-estradiol exerts anticancer effects in anoikis-resistant hepatocellular carcinoma cell lines by targeting IL-6/STAT3 signaling

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seulki, E-mail: sl10f@naver.com [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Lee, Minjong, E-mail: minjonglee2@naver.com [Division of Gastroenterology, Department of Internal Medicine, Kangwon National University Hospital, 156 Baengnyeong-ro, Chuncheon-si, Gangwon-do (Korea, Republic of); Kim, Jong Bin, E-mail: kkimjp@hanmail.net [Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN, 55912 (United States); Jo, Ara, E-mail: loveara0315@naver.com [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Cho, Eun Ju, E-mail: creatioex@gmail.com [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Yu, Su Jong, E-mail: ydoctor2@hanmail.net [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Lee, Jeong-Hoon, E-mail: pindra@empal.com [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Yoon, Jung-Hwan, E-mail: yoonjh@snu.ac.kr [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Kim, Yoon Jun, E-mail: yoonjun@snu.ac.kr [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of)

    2016-05-13

    17β-Estradiol (E2) has been proven to exert protective effects against HCC; however, its mechanism on HCC proliferation and suppression of invasion remains to be further explored. Because HCC up-regulates serum Interleukin-6 (IL-6) levels and Signal Transducer and Activator of Transcription 3 (STAT3), molecular agents that attenuate IL-6/STAT3 signaling can potentially suppress HCC development. In this study, we examined involvement of E2 in anoikis resistance that induces invasion capacities and chemo-resistance. Huh-BAT and HepG2 cells grown under anchorage-independent condition were selected. The anoikis-resistant (AR) cells showed stronger chemo-resistance against sorafenib, doxorubicin, 5-fluorouracil and cisplatin compared to adherent HCC cells. AR HCC cells exhibited decreased expression of E-cadherin and increased expression of the N-cadherin and vimentin compared to adherent HCC cells. We then demonstrated that E2 suppressed cell proliferation in AR HCC cells. IL-6 treatment enhanced invasive characteristics, and E2 reversed it. Regarding mechanism of E2, it decreased in the phosphorylation of STAT3 that overexpressed on AR HCC cells. The inhibitory effect of E2 on cell growth was accompanied with cell cycle arrest at G2/M phase and caspase-3/9/PARP activation through c-Jun N-terminal Kinase (JNK) phosphorylation. Taken together, these findings suggested that E2 inhibited the proliferation of AR HCC cells through down-regulation of IL-6/STAT3 signaling. Thus, E2 can be a potential therapeutic drug for treatment of metastatic or chemo-resistant HCC. -- Highlights: •Anoikis-resistant HCC cells characterized chemo-resistant and metastatic potentials. •17β-Estradiol down-regulated IL-6/STAT3 signaling in anoikis-resistant HCC cells. •17β-Estradiol suppressed cell proliferation by inducing G2/M phase arrest and apoptosis though JNK phosphorylation.

  2. In vitro investigating of anticancer activity of focuxanthin from marine brown seaweed species

    Directory of Open Access Journals (Sweden)

    M. Karkhane Yousefi

    2018-01-01

    Full Text Available Breast cancer is the most common cancer type among women all over the world. Chemotherapy is the use of anticancer medicines for treating cancer but it has many side effects and cells may become resistant to these chemical medicines. Therefore, finding new compounds of natural origin could be a promising solution to this problem. The aim of the current study was to evaluate anticancer activity of fucoxanthin which is the most important carotenoid found in the marine brown seaweeds and diatoms. fucoxanthin has many properties (antioxidant, antibacterial, anticancer, antiobesity, anti-inflammatory and etc. due to its unique structure. Samples with different concentrations (10, 25 and 50 µg/ml and at various incubation times were collected (6, 24 and 48 hours from four different species (Padina tenuis, Colpomenia sinuosa, Iyengaria stellate and Dictyota indica of brown seaweeds from Qeshm Island, Persian Gulf. Moreover, the anticancer activity of fucoxanthin-containing extracts on breast cancer cells line and normal human skin fibroblast cells line was assessed by MTT [3-(4,5-dimethylthiazolyl-2,5-diphenyl-tetrazolium bromide] assay to specify the cytotoxic effects. The results showed that fucoxanthin extract from Dictyota. indica at 24-hour treatment and 50 µg/ml concentration has the most effective anticancer activity on the breast cancer cells line, without toxic effects to the normal cells. According to the obtained results, it seems that Dictyota. Indica is a good candidate for further analysis and can be introduced to the food and pharmaceutical industries.

  3. Impact of dosage timing on the bioavailability of oral anticancer medications: Is pre-prandial dosing equivalent to post-prandial dosing.

    Science.gov (United States)

    Yu, Guo; Wu, Dan-Na; Yu, Yichao; Li, Guo-Fu; Zhou, Hong-Hao

    2018-01-01

    Many oral anticancer agents are recommended to be given either at least 1 h before or 2 h after a meal, according to the prescribing information. However, the effect of dosage timing of an oral anticancer agent with reference to food intake on anticancer treatment remains unclear. As shown by the literature survey and labeling analysis for oral anticancer drugs approved by the US Food and Drug Administration from 2010 to 2016, labeling information regarding dosage timing for several anticancer drugs appeared not be optimum, leading to suboptimal bioavailability and plasma drug concentrations. This supports a call to regularly recalibrate the labeling information for dosage timing of oral anticancer medications to minimize the risks of compromised efficacy or unintended toxicities.

  4. Dietary Nanosized Lactobacillus plantarum Enhances the Anticancer Effect of Kimchi on Azoxymethane and Dextran Sulfate Sodium-Induced Colon Cancer in C57BL/6J Mice.

    Science.gov (United States)

    Lee, Hyun Ah; Kim, Hyunung; Lee, Kwang-Won; Park, Kun-Young

    2016-01-01

    This study was undertaken to evaluate enhancement of the chemopreventive properties of kimchi by dietary nanosized Lactobacillus (Lab.)plantarum (nLp) in an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis-associated colorectal cancer C57BL/6J mouse model. nLp is a dead, shrunken, processed form of Lab. Plantarum isolated from kimchi that is 0.5-1.0 µm in size. The results obtained showed that animals fed kimchi with nLp (K-nLp) had longer colons and lower colon weights/length ratios and developed fewer tumors than mice fed kimchi alone (K). In addition, K-nLp administration reduced levels of proinflammatory cytokine serum levels and mediated the mRNA and protein expressions of inflammatory, apoptotic, and cell-cycle markers to suppress inflammation and induce tumor-cell apoptosis and cell-cycle arrest. Moreover, it elevated natural killer-cell cytotoxicity. The study suggests adding nLp to kimchi could improve the suppressive effect of kimchi on AOM/DSS-induced colorectal cancer. These findings indicate nLp has potential use as a functional chemopreventive ingredient in the food industry.

  5. Synthesis and Characterization of Two New Thiophene Acetyl Salicylic Acid Esters and their ortho- and para-effect on Anticancer Activity.

    Science.gov (United States)

    Unver, Hakan; Canturk, Zerrin

    2017-01-01

    The present study aimed to explore the cytotoxic effect of ortho- and para-positional isomers of thiophene acetyl salicylic acid esters against cancer and normal cell lines. Two new thiophene-2-acetic acid esters (2-((2-(thiophen-2-yl)acetyl)thio)benzoic acid and 4-((2-(thiophen-2- yl)acetyl)thio)benzoic acid) were synthesized and characterized by Elemental analysis, Fourier transform infrared spectroscopy, 1H-nuclear magnetic resonance (NMR), 13C-NMR and High-resolution mass spectroscopy. The compounds were tested for their in vitro cytotoxic activity against A549 and Caco2 tumor cell lines and CCD- 19Lu and CCD 841 CoN normal cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,4,diphenyltetrazolium bromide assay. 2-((2-(thiophene-2-yl)acetyl)thio)benzoic acid showed a higher activity with (IC50 = 239.88µM/mL) compared with a reference drug nearly as active as cyclophosphamide (IC50 = 257.11 µM/mL) on Caco2 cell line. Apoptosis was observed by flow cytometric analysis on Caco2 cells. Thus, positional isomerism is critical for the pharmacological properties of thiophene acetyl salicylic acid esters against colon cancer cell line compared with nonsmall cell lung cancer cell line. The ortho-isomer induced cell death and was much more potent than the para-isomer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Randomized anticancer and cytotoxicity activities of Guibourtia ...

    African Journals Online (AJOL)

    Materials and Methods: The plants were screened for the presence of coumarins, alkaloids, flavonoids, anthraquinones, steroids and terpenoids using thin layer chromatography. Anticancer screening was performed on a panel of three cancer cell lines, while cytotoxicity was determined using a human fibroblast cell line, ...

  7. Anticancer and antiproliferative activity of natural brassinosteroids

    Czech Academy of Sciences Publication Activity Database

    Malíková, J.; Swaczynová, Jana; Kolář, Z.; Strnad, Miroslav

    2008-01-01

    Roč. 69, č. 2 (2008), s. 418-426 ISSN 0031-9422 Institutional research plan: CEZ:AV0Z50380511 Keywords : Brassinosteroids * Anticancer activity * Cell cycle Subject RIV: CE - Biochemistry Impact factor: 2.946, year: 2008

  8. Early clinical development of targeted anticancer agents

    NARCIS (Netherlands)

    van Brummelen, E.M.J.

    2017-01-01

    Van Brummelen studied the safety and preliminary signs of efficacy of several novel targeted anticancer agents in phase I trials. In her thesis, she reports the results of trials with the immunotherapies pembrolizumab and cergutuzumab-amunaleukin, and with combinations of inhibitors of the MEK and

  9. PEGylated Silk Nanoparticles for Anticancer Drug Delivery

    DEFF Research Database (Denmark)

    Wongpinyochit, Thidarat; Uhlmann, Petra; Urquhart, Andrew

    2015-01-01

    clinically established and emerging anticancer drugs. Overall, PEGylated silk nanoparticles showed high encapsulation efficiency (>93%) and a pH-dependent release over 14 days. Finally, we demonstrated significant cytotoxicity of drug loaded silk nanoparticles applied as single and combination nanomedicines...

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

    Science.gov (United States)

    Jo, Miran; Park, Mi Hee; Kollipara, Pushpa Saranya; An, Byeong Jun; Song, Ho Sueb; Han, Sang Bae; Kim, Jang Heub; Song, Min Jong; Hong, Jin Tae

    2012-01-01

    We investigated whether bee venom and melittin, a major component of bee venom, inhibit cell growth through enhancement of death receptor expressions in the human ovarian cancer cells, SKOV3 and PA-1. Bee venom (1-5 μg/ml) and melittin (0.5-2 μg/ml) inhibited the growth of SKOV3 and PA-1 ovarian cancer cells by the induction of apoptotic cell death in a dose dependent manner. Consistent with apoptotic cell death, expression of death receptor (DR) 3 and DR6 was increased in both cancer cells, but expression of DR4 was increased only in PA-1 cells. Expression of DR downstream pro-apoptotic proteins including caspase-3, 8, and Bax was concomitantly increased, but the phosphorylation of JAK2 and STAT3 and the expression of Bcl-2 were inhibited by treatment with bee venom and melittin in SKOV3 and PA-1 cells. Expression of cleaved caspase-3 was increased in SKOV3, but cleaved caspase-8 was increased in PA-1 cells. Moreover, deletion of DR3, DR4, and DR6 by small interfering RNA significantly reversed bee venom and melittin-induced cell growth inhibitory effect as well as down regulation of STAT3 by bee venom and melittin in SKOV3 and PA-1 ovarian cancer cell. These results suggest that bee venom and melittin induce apoptotic cell death in ovarian cancer cells through enhancement of DR3, DR4, and DR6 expression and inhibition of STAT3 pathway. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. SRJ09, a promising anticancer drug lead: Elucidation of mechanisms of antiproliferative and apoptogenic effects and assessment of in vivo antitumor efficacy.

    Science.gov (United States)

    Wong, Charng Choon; Lim, Siang Hui; Sagineedu, Sreenivasa Rao; Lajis, Nordin Haji; Stanslas, Johnson

    2016-05-01

    SRJ09 (3,19-(2-bromobenzylidene)andrographolide), a semisynthetic andrographolide (AGP) derivative, was shown to induce G1 cell cycle arrest and eventually apoptosis in breast and colon cancer cell lines. The present investigation was carried out to elucidate the mechanisms cell cycle arrest and apoptosis and evaluate the in vivo antitumor activity of SRJ09. The in vitro growth inhibitory properties of compounds were assessed in colon (HCT-116) and breast (MCF-7) cancer cell lines. Immunoblotting was utilized to quantitate the protein levels in cells. The gene expressions were determined using reverse transcriptase PCR (RT-PCR). Pharmacokinetic investigation was carried out by determining SRJ09 levels in plasma of Balb/C mice using HPLC. In vivo antitumor activity was evaluated in athymic mice carrying HCT-116 colon tumor xenografts. SRJ09 displayed improved in vitro activity when compared with AGP by producing rapid cell killing effect in vitro. Its activity was not compromised in MES-SA/Dx5 multidrug resistant (MDR) cells expressing p-glycoprotein. Cells treated with SRJ09 (0.1-10μM) displayed increased p21 protein level, which corresponded with gene expression. Whereas CDK4 protein level and gene expression was suppressed. The treatment did not affect cyclin D1. Changes of these proteins paralleled G1 cell cycle arrest in both cell lines as determined by flow cytometry. Induction of apoptosis by SRJ09 in HCT-116 cells which occurred independent of p53 and bcl-2 was inhibited in the presence of caspase 8 inhibitor, implicating the extrinsic apoptotic pathway. A single dose (100mg/kg, i.p) of SRJ09 produced a plasma concentration range of 12-30.4μM. At 400mg/kg (q4dX3), it significantly retarded growth of tumor xenografts. The antitumor activity of SRJ09 is suggested mediated via the induction of p21 expression and suppression of CDK-4 expression without affecting cyclin D1 to trigger G1 arrest leading to apoptosis. Copyright © 2016 Elsevier Ltd. All rights

  12. Positive effects on hematological and biochemical imbalances in patients with metastatic breast cancer stage IV, of BP-C1, a new anticancer substance

    Directory of Open Access Journals (Sweden)

    Lindkær-Jensen S

    2015-03-01

    Full Text Available Steen Lindkær-Jensen,1 Stig Larsen,2 Nina Habib-Lindkær-Jensen,1 Hans E Fagertun3 1Department of Surgery and Cancer, Hammersmith Hospital Campus, Imperial College, London, UK; 2Center of Epidemiology and Biostatistics, Faculty of Veterinary Medicine, University of Life Science, Oslo, Norway; 3Meddoc Research AS, Skjetten, Norway Abstract: A benzene-poly-carboxylic acid complex with cis-diammineplatinum(II dihydrocholride, BP-C1 is currently used in clinical trials in treating metastatic breast cancer. BP-C1 controls tumor growth with a few mild side-effects, improving quality of life.Methods: The data consisted of prospectively collected laboratory results from 47 patients in two controlled clinical trials of daily intramuscular injections of BP-C1 for 32 days. Study I was performed as an open, nonrandomized, Phase I dose–response, multicenter study with a three-level, between-patient, response surface pathway design. The second study was a randomized, double-blind, and placebo-controlled, multicenter study with a stratified semi-crossover design.Results: Hemoglobin (Hb and hematocrit (Hct increased significantly (P<0.01 during BP-C1 treatment, while red blood cell (RBC count increased but not significantly. The most pronounced increase in Hb, RBC, Hct, and white blood cell (WBC was in anemic patients (P≤0.01. WBC count and neutrophils increased significantly (P=0.01 in the overall data. WBCs and neutrophils (P<0.01, eosinophils (P=0.05 and monocytes (P<0.01 increased significantly and markedly in patients with lowest baseline levels. Additionally, low levels of thrombocytes significantly increased. No changes in liver parameters, amylase, glucose, creatinine, or albumin, were detected except for albumin in the subgroup with low baseline levels, where levels increased significantly (P=0.04. An increase in K+, Ca2+, and PO43- was most pronounced in patients with low baseline levels (P≤0.02. A similar pattern detected for Mg2+, prothrombin

  13. Preparation, characterization and in vitro release kinetics of polyaspartamide-based conjugates containing antimalarial and anticancer agents for combination therapy

    CSIR Research Space (South Africa)

    Aderibigbe, BA

    2016-09-01

    Full Text Available Malaria is treated by combination of two drugs in order to overcome drug resistance. Antimalarials have been found to be more effective by combining them with low doses of anticancer drugs. Polymer-drug conjugates containing aminoquinoline...

  14. 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

  15. Anticancer activity of Ficus religiosa engineered copper oxide nanoparticles

    International Nuclear Information System (INIS)

    Sankar, Renu; Maheswari, Ramasamy; Karthik, Selvaraju; Shivashangari, Kanchi Subramanian; Ravikumar, Vilwanathan

    2014-01-01

    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

  16. 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.

  17. Down-regulation of 14-3-3β exerts anti-cancer effects through inducing ER stress in human glioma U87 cells: Involvement of CHOP–Wnt pathway

    International Nuclear Information System (INIS)

    Cao, Lei; Lei, Hui; Chang, Ming-Ze; Liu, Zhi-Qin; Bie, Xiao-Hua

    2015-01-01

    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

  18. Controlling the transcription levels of argGH redistributed L-arginine metabolic flux in N-acetylglutamate kinase and ArgR-deregulated Corynebacterium crenatum.

    Science.gov (United States)

    Zhao, Qinqin; Luo, Yuchang; Dou, Wenfang; Zhang, Xian; Zhang, Xiaomei; Zhang, Weiwei; Xu, Meijuan; Geng, Yan; Rao, Zhiming; Xu, Zhenghong

    2016-01-01

    Corynebacterium crenatum SYPA5-5, an L-arginine high-producer obtained through multiple mutation-screening steps, had been deregulated by the repression of ArgR that inhibits L-arginine biosynthesis at genetic level. Further study indicated that feedback inhibition of SYPA5-5 N-acetylglutamate kinase (CcNAGK) by L-arginine, as another rate-limiting step, could be deregulated by introducing point mutations. Here, we introduced two of the positive mutations (H268N or R209A) of CcNAGK into the chromosome of SYPA5-5, however, resulting in accumulation of large amounts of the intermediates (L-citrulline and L-ornithine) and decreased production of L-arginine. Genetic and enzymatic levels analysis involved in L-arginine biosynthetic pathway of recombinants SYPA5-5-NAGKH268N (H-7) and SYPA5-5-NAGKR209A (R-8) showed that the transcription levels of argGH decreased accompanied with the reduction of argininosuccinate synthase and argininosuccinase activities, respectively, which led to the metabolic obstacle from L-citrulline to L-arginine. Co-expression of argGH with exogenous plasmid in H-7 and R-8 removed this bottleneck and increased L-arginine productivity remarkably. Compared with SYPA5-5, fermentation period of H-7/pDXW-10-argGH (H-7-GH) reduced to 16 h; meanwhile, the L-arginine productivity improved about 63.6%. Fed-batch fermentation of H-7-GH in 10 L bioreactor produced 389.9 mM L-arginine with the productivity of 5.42 mM h(-1). These results indicated that controlling the transcription of argGH was a key factor for regulating the metabolic flux toward L-arginine biosynthesis after deregulating the repression of ArgR and feedback inhibition of CcNAGK, and therefore functioned as another regulatory mode for L-arginine production. Thus, deregulating all these three regulatory modes was a powerful strategy to construct L-arginine high-producing C. crenatum.

  19. Inhibitory effect of berberine on the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2

    International Nuclear Information System (INIS)

    Peng, P.-L.; Hsieh, Y.-S.; Wang, C.-J.; Hsu, J.-L.; Chou, F.-P.

    2006-01-01

    Berberine, a compound isolated from medicinal herbs, has been reported with many pharmacological effects related to anti-cancer and anti-inflammation capabilities. In this study, we observed that berberine exerted a dose- and time-dependent inhibitory effect on the motility and invasion ability of a highly metastatic A549 cells under non-cytotoxic concentrations. In cancer cell migration and invasion process, matrix-degrading proteinases are required. A549 cell treated with berberine at various concentrations showed reduced ECM proteinases including matrix metalloproteinase-2 (MMP2) and urokinase-plasminogen activator (u-PA) by gelatin and casein zymography analysis. The inhibitory effect is likely to be at the transcriptional level, since the reduction in the transcripts levels was corresponding to the proteins. Moreover, berberine also exerted its action via regulating tissue inhibitor of metalloproteinase-2 (TIMP-2) and urokinase-plasminogen activator inhibitor (PAI). The upstream mediators of the effect involved c-jun, c-fos and NF-κB, as evidenced by reduced phosphorylation of the proteins. These findings suggest that berberine possesses an anti-metastatic effect in non-small lung cancer cell and may, therefore, be helpful in clinical treatment

  20. Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles.

    Science.gov (United States)

    Chang, Ji-Eun; Cho, Hyun-Jong; Jheon, Sanghoon

    2016-12-01

    Photodynamic therapy (PDT) is a non-invasive and non-surgical method representing an attractive alternative choice for lung cancer treatment. Photosensitizers selectively accumulate in tumor tissue and lead to tumor cell death in the presence of oxygen and the proper wavelength of light. To increase the therapeutic effect of PDT, we developed both photosensitizer- and anticancer agent-loaded lung cancer-targeted nanoparticles. Both enhanced permeability and retention (EPR) effect-based passive targeting and hyaluronic-acid-CD44 interaction-based active targeting were applied. CD44 is a well-known hyaluronic acid receptor that is often introduced as a biomarker of non-small cell lung cancer. In addition, a combination of PDT and chemotherapy is adopted in the present study. This combination concept may increase anticancer therapeutic effects and reduce adverse reactions. We chose hypocrellin B (HB) as a novel photosensitizer in this study. It has been reported that HB causes higher anticancer efficacy of PDT compared to hematoporphyrin derivatives 1 . Paclitaxel was selected as the anticancer drug since it has proven to be a potential treatment for lung cancer 2 . The antitumor efficacies of photosensitizer (HB) solution, photosensitizer encapsulated hyaluronic acid-ceramide nanoparticles (HB-NPs), and both photosensitizer- and anticancer agent (paclitaxel)-encapsulated hyaluronic acid-ceramide nanoparticles (HB-P-NPs) after PDT were compared both in vitro and in vivo. The in vitro phototoxicity in A549 (human lung adenocarcinoma) cells and the in vivo antitumor efficacy in A549 tumor-bearing mice were evaluated. The HB-P-NP treatment group showed the most effective anticancer effect after PDT. In conclusion, the HB-P-NPs prepared in the present study represent a potential and novel photosensitizer delivery system in treating lung cancer with PDT.

  1. Cranberry as promising natural source of potential anticancer agents: current evidence and future perspectives.

    Science.gov (United States)

    Katsargyris, Athanasios; Tampaki, Ekaterini-Christina; Giaginis, Constantinos; Theocharis, Stamatios

    2012-07-01

    Accumulating evidence suggest that dietary modification can lower the risk for several cancer types' development. Cranberry in particular, has been shown to have anti-oxidative, -inflammatory and -proliferative properties in vitro. To present the latest knowledge regarding the role of cranberry extracts against human cancer several types. A review of the literature documenting both in vitro and in vivo anti-cancer effects of whole cranberry and/or its extracts is conducted. Current data provide evidence for several anti-cancer properties of either whole cranberry and/or its extracts. The discovery of the specific cranberry components and the appropriate concentrations that exert such beneficial effects along with verification of the preliminary in vitro results in in vivo settings could potentially lead to the invention of novel safer and efficient anti-cancer therapeutic agents.

  2. 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.

  3. 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.

  4. Germane facts about germanium sesquioxide: I. Chemistry and anticancer properties.

    Science.gov (United States)

    Kaplan, Bonnie J; Parish, W Wesley; Andrus, G Merrill; Simpson, J Steven A; Field, Catherine J

    2004-04-01

    This paper reviews the history, chemistry, safety, toxicity, and anticancer effects of the organogermanium compound bis (2-carboxyethylgermanium) sesquioxide (CEGS). A companion review follows, discussing the inaccuracies in the scientific record that have prematurely terminated research on clinical uses of CEGS. CEGS is a unique organogermanium compound first made by Mironov and coworkers in Russia and, shortly thereafter, popularized by Asai and his colleagues in Japan. Low concentrations of germanium occur in nearly all soils, plants and animal life; natural occurrence of the CEGS form is postulated but not yet demonstrated. The literature demonstrating its anticancer effect is particularly strong: CEGS induces interferon-gamma (IFN-gamma), enhances natural killer cell activity, and inhibits tumor and metastatic growth--effects often detectable after a single oral dose. In addition, oral consumption of CEGS is readily assimilated and rapidly cleared from the body without evidence of toxicity. Given these findings, the absence of human clinical trials of CEGS is unexpected. Possible explanations of why the convincing findings from animal research have not been used to support clinical trials are discussed. Clinical trials on CEGS are recommended.

  5. A one-pot laccase-catalysed synthesis of coumestan derivatives and their anticancer activity

    CSIR Research Space (South Africa)

    Qwebani-Ogunleye, Tozama

    2016-12-01

    Full Text Available screened against renal TK10, melanoma UACC62 and breast MCF7 cancer cell-lines and the GI50, TGI and LC50 values determined. Anticancer screening showed that the cytostatic effects of the coumestans were most effective against the melanoma UACC62 and breast...

  6. Nanomelatonin triggers superior anticancer functionality in a human malignant glioblastoma cell line

    Science.gov (United States)

    Yadav, Sanjeev Kumar; Srivastava, Anup Kumar; Dev, Atul; Kaundal, Babita; Choudhury, Subhasree Roy; Karmakar, Surajit

    2017-09-01

    Melatonin (MEL) has promising medicinal value as an anticancer agent in a variety of malignancies, but there are difficulties in achieving a therapeutic dose due to its short half-life, low bioavailability, poor solubility and extensive first-pass metabolism. In this study chitosan/tripolyphosphate (TPP) nanoparticles were prepared by an ionic gelation method to overcome the therapeutic challenges of melatonin and to improve its anticancer efficacy. Characterization of the melatonin-loaded chitosan (MEL-CS) nanoformulation was performed using transmission and scanning electron microscopies, dynamic light scattering, Fourier transform infrared spectroscopy, Raman spectroscopy and x-ray diffraction. In vitro release, cellular uptake and efficacy studies were tested for their enhanced anticancer potential in human U87MG glioblastoma cells. Confocal studies revealed higher cellular uptake of MEL-CS nanoparticles and enhanced anticancer efficacy in human malignant glioblastoma cancer cells than in healthy non-malignant human HEK293T cells in mono- and co-culture models. Our study has shown for the first time that MEL-CS nanocomposites are therapeutically more effective as compared to free MEL at inducing functional anticancer efficacy in the human brain tumour U87MG cell line.

  7. Plant Secondary Metabolites as Anticancer Agents: Successes in Clinical Trials and Therapeutic Application

    Directory of Open Access Journals (Sweden)

    Ana M. L. Seca

    2018-01-01

    Full Text Available Cancer is a multistage process resulting in an uncontrolled and abrupt division of cells and is one of the leading causes of mortality. The cases reported and the predictions for the near future are unthinkable. Food and Drug Administration data showed that 40% of the approved molecules are natural compounds or inspired by them, from which, 74% are used in anticancer therapy. In fact, natural products are viewed as more biologically friendly, that is less toxic to normal cells. In this review, the most recent and successful cases of secondary metabolites, including alkaloid, diterpene, triterpene and polyphenolic type compounds, with great anticancer potential are discussed. Focusing on the ones that are in clinical trial development or already used in anticancer therapy, therefore successful cases such as paclitaxel and homoharringtonine (in clinical use, curcumin and ingenol mebutate (in clinical trials will be addressed. Each compound’s natural source, the most important steps in their discovery, their therapeutic targets, as well as the main structural modifications that can improve anticancer properties will be discussed in order to show the role of plants as a source of effective and safe anticancer drugs.

  8. An Insight into the Anticancer Activities of Ru(II-Based Metallocompounds Using Docking Methods

    Directory of Open Access Journals (Sweden)

    Peter A. Ajibade

    2013-09-01

    Full Text Available Unlike organic molecules, reports on docking of metal complexes are very few; mainly due to the inadequacy of force fields in docking packages to appropriately characterize the metal atoms that consequentially hinder the rational design of metal-based drug complexes. In this study we have made used Molegro and Autodock to predict the anticancer activities of selected Ru(II complexes against twelve anticancer targets. We observed that introducing the quantum calculated atomic charges of the optimized geometries significantly improved the docking predictions of these anticancer metallocompounds. Despite several limitations in the docking of metal-based complexes, we obtained results that are highly correlated with the available experimental results. Most of our newly proposed metallocompounds are found theoretically to be better anticancer metallocompounds than all the experimentally proposed RAPTA complexes. An interesting features of a strong interactions of new modeled of metallocompounds against the two base edges of DNA strands suggest similar mechanisms of anticancer activities similar to that of cisplatin. There is possibility of covalent bonding between the metal center of the metallocompounds and the residues of the receptors DNA-1, DNA-2, HDAC7, HIS and RNR. However, the general results suggest the possibility of metals positioning the coordinated ligands in the right position for optimal receptor interactions and synergistic effects, rather than forming covalent bonds.

  9. Quinonaphthothiazines, syntheses, structures and anticancer activities

    Science.gov (United States)

    Jeleń, M.; Pluta, K.; Suwińska, K.; Morak-Młodawska, B.; Latocha, M.; Shkurenko, A.

    2015-11-01

    Two new types of pentacyclic azaphenothiazines being quinonaphthothiazines were obtaining from the reactions of dichlorodiquinolinyl disulfide with 1- and 2-naphthylamines. As the reactions could proceed in many ways, the proper structure elucidation was crucial. The structure determination was based on the 2D NMR spectra (NOESY, HSQC and HMBC) of the methyl derivatives. The final structure evidences came from X-ray analysis of the monocrystals. The new quinonaphthothiazines represent angularly fused pentacyclic ring systems which is folded along the N-S axis. The parent NH-compounds were transformed into the N-derivatives. Some quinonaphthothiazines exhibited promising anticancer activity against glioblastoma SNB-19, melanoma C-32 and human ductal breast epithelial tumor T47D cell lines. The anticancer activity dependent on the nature of the substituents and the ring fusion between the thiazine and naphthalene moieties. Two compounds were more active than the reference drug, cisplatin.

  10. Some medicinal plants as natural anticancer agents

    OpenAIRE

    Govind Pandey; S Madhuri

    2009-01-01

    India is the largest producer of medicinal plants and is rightly called the "Botanical garden of the World". The medicinal plants, besides having natural therapeutic values against various diseases, also provide high quality of food and raw materials for livelihood. Considerable works have been done on these plants to treat cancer, and some plant products have been marketed as anticancer drugs, based on the traditional uses and scientific reports. These plants may promote host resistance agai...

  11. Proteomics of anti-cancer drugs

    Czech Academy of Sciences Publication Activity Database

    Kovářová, Hana; Martinková, Jiřina; Hrabáková, Rita; Skalníková, Helena; Novák, Petr; Hajdůch, M.; Gadher, S. J.

    2009-01-01

    Roč. 276, Supplement 1 (2009), s. 84-84 E-ISSN 1742-4658. [34th FEBS Congress. 04.07.2009-09.07.2009, Praha] R&D Projects: GA MŠk LC07017 Institutional research plan: CEZ:AV0Z50450515; CEZ:AV0Z50200510 Keywords : proteomics * anti-cancer drugs * biomarkers Subject RIV: FD - Oncology ; Hematology

  12. Nitroxides as Antioxidants and Anticancer Drugs

    Directory of Open Access Journals (Sweden)

    Marcin Lewandowski

    2017-11-01

    Full Text Available Nitroxides are stable free radicals that contain a nitroxyl group with an unpaired electron. In this paper, we present the properties and application of nitroxides as antioxidants and anticancer drugs. The mostly used nitroxides in biology and medicine are a group of heterocyclic nitroxide derivatives of piperidine, pyrroline and pyrrolidine. The antioxidant action of nitroxides is associated with their redox cycle. Nitroxides, unlike other antioxidants, are characterized by a catalytic mechanism of action associated with a single electron oxidation and reduction reaction. In biological conditions, they mimic superoxide dismutase (SOD, modulate hemoprotein’s catalase-like activity, scavenge reactive free radicals, inhibit the Fenton and Haber-Weiss reactions and suppress the oxidation of biological materials (peptides, proteins, lipids, etc.. The use of nitroxides as antioxidants against oxidative stress induced by anticancer drugs has also been investigated. The application of nitroxides and their derivatives as anticancer drugs is discussed in the contexts of breast, hepatic, lung, ovarian, lymphatic and thyroid cancers under in vivo and in vitro experiments. In this article, we focus on new natural spin-labelled derivatives such as camptothecin, rotenone, combretastatin, podophyllotoxin and others. The applications of nitroxides in the aging process, cardiovascular disease and pathological conditions were also discussed.

  13. Phytochemicals as Anticancer and Chemopreventive Topoisomerase II Poisons

    Science.gov (United States)

    Ketron, Adam C.

    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 topoisomerase II to a cellular toxin that fragments the genome. Because of their mode of action, they are referred to as topoisomerase II poisons as opposed to catalytic inhibitors. The first sections of this article discuss DNA topology, the catalytic cycle of topoisomerase II, and the two mechanisms (interfacial vs. covalent) by which different classes of topoisomerase II poisons alter enzyme activity. Subsequent sections discuss the effects of several phytochemicals on the type II enzyme, including demethyl-epipodophyllotoxins (semisynthetic anticancer drugs) as well as flavones, flavonols, isoflavones, catechins, isothiocyanates, and curcumin (dietary chemopreventive agents). Finally, the leukemogenic potential of topoisomerase II-targeted phytochemicals is described. PMID:24678287

  14. Anti-Cancer Drug Delivery Using Carbohydrate-Based Polymers.

    Science.gov (United States)

    Ranjbari, Javad; Mokhtarzadeh, Ahad; Alibakhshi, Abbas; Tabarzad, Maryam; Hejazi, Maryam; Ramezani, Mohammad

    2018-02-12

    Polymeric drug delivery systems in the form of nanocarriers are the most interesting vehicles in anticancer therapy. Among different types of biocompatible polymers, carbohydrate-based polymers or polysaccharides are the most common natural polymers with complex structures consisting of long chains of monosaccharide or disaccharide units bound by glycosidic linkages. Their appealing properties such as availability, biocompatibility, biodegradability, low toxicity, high chemical reactivity, facile chemical modification and low cost led to their extensive applications in biomedical and pharmaceutical fields including development of nano-vehicles for delivery of anti-cancer therapeutic agents. Generally, reducing systemic toxicity, increasing short half-lives and tumor localization of agents are the top priorities for a successful cancer therapy. Polysaccharide-based or - coated nanosystems with respect to their advantageous features as well as accumulation in tumor tissue due to enhanced permeation and retention (EPR) effect can provide promising carrier systems for the delivery of noblest impressive agents. Most challenging factor in cancer therapy was the toxicity of anti-cancer therapeutic agents for normal cells and therefore, targeted delivery of these drugs to the site of action can be considered as an interesting therapeutic strategy. In this regard, several polysaccharides exhibited selective affinity for specific cell types, and so they can act as a targeting agent in drug delivery systems. Accordingly, different aspects of polysaccharide applications in cancer treatment or diagnosis were reviewed in this paper. In this regard, after a brief introduction of polysaccharide structure and its importance, the pharmaceutical usage of carbohydrate-based polymers was considered according to the identity of accompanying active pharmaceutical agents. It was also presented that the carbohydrate based polymers have been extensively considered as promising materials in

  15. Gene signature critical to cancer phenotype as a paradigm for anticancer drug discovery.

    Science.gov (United States)

    Sampson, E R; McMurray, H R; Hassane, D C; Newman, L; Salzman, P; Jordan, C T; Land, H

    2013-08-15

    Malignant cell transformation commonly results in the deregulation of thousands of cellular genes, an observation that suggests a complex biological process and an inherently challenging scenario for the development of effective cancer interventions. To better define the genes/pathways essential to regulating the malignant phenotype, we recently described a novel strategy based on the cooperative nature of carcinogenesis that focuses on genes synergistically deregulated in response to cooperating oncogenic mutations. These so-called 'cooperation response genes' (CRGs) are highly enriched for genes critical for the cancer phenotype, thereby suggesting their causal role in the malignant state. Here, we show that CRGs have an essential role in drug-mediated anticancer activity and that anticancer agents can be identified through their ability to antagonize the CRG expression profile. These findings provide proof-of-concept for the use of the CRG signature as a novel means of drug discovery with relevance to underlying anticancer drug mechanisms.

  16. Anticancer Activities of Surfactin and Potential Application of Nanotechnology Assisted Surfactin Delivery

    Directory of Open Access Journals (Sweden)

    Yuan-Seng Wu

    2017-10-01

    Full Text Available Surfactin, a cyclic lipopeptide biosurfactant produced by various strains of Bacillus genus, has been shown to induce cytotoxicity against many cancer types, such as Ehrlich ascites, breast and colon cancers, leukemia and hepatoma. Surfactin treatment can inhibit cancer progression by growth inhibition, cell cycle arrest, apoptosis, and metastasis arrest. Owing to the potent effect of surfactin on cancer cells, numerous studies have recently investigated the mechanisms that underlie its anticancer activity. The amphiphilic nature of surfactin allows its easy incorporation nano-formulations, such as polymeric nanoparticles, micelles, microemulsions, liposomes, to name a few. The use of nano-formulations offers the advantage of optimizing surfactin delivery for an improved anticancer therapy. This review focuses on the current knowledge of surfactin properties and biosynthesis; anticancer activity against different cancer models and the underlying mechanisms involved; as well as the potential application of nano-formulations for optimal surfactin delivery.

  17. In vitro method determing sensitivity of anticancer agents by incorporation of radioactive precursors

    International Nuclear Information System (INIS)

    Sakakibara, Satoshi

    1983-01-01

    A new sensitivity test of anticancer agents was developed to measure the lethal effects of cancer cells by the incorporation of radioactive precursors. The thousand cancer cells were cultured in a microplate in the presence of anticancer agents. These cells were exposed to radioactive precursors. Two or three days later, the cancer cells were harvested on a glass fiver filter by a multiple automatic cell-harvester and the incorporation of precursors was counted by a liquid scintillation counter. In this study, the in vivo results of drug testing in animal model systems were compared with drug sensitivities. Mice inoculated Ehrlich ascites cells were treated with various kinds of anticancer drugs. The development of the cells was compatible with the result of the sensitivity test. The growths of Lauson and ME-180 cells derived from human cancers implanted subcutaneously to nude mice were also well correlated with this sensitivity test. (author)

  18. The Severity of Plasmodium falciparum infection is associated with transcript levels of var genes encoding endothelial protein C receptor-binding P. falciparum erythrocyte membrane protein 1

    DEFF Research Database (Denmark)

    Mkumbaye, Sixbert I; Wang, Christian W; Lyimo, Eric

    2017-01-01

    importance of different subtypes of CIDRα1 domains, we compared Pfemp1 transcript levels in children with severe malaria (including 9 fatal and 114 surviving cases), children hospitalized with uncomplicated malaria (n = 42), children with mild malaria not requiring hospitalization (n = 10), and children...... the PfEMP1-EPCR interaction by vaccines and adjunctive therapies. Interventions should target EPCR binding of all CIDRα1 subtypes....

  19. Evaluation of transcription levels of inlA, inlB, hly, bsh and prfA genes in Listeria monocytogenes strains using quantitative reverse-transcription PCR and ability of invasion into human CaCo-2 cells.

    Science.gov (United States)

    Tamburro, Manuela; Sammarco, Michela Lucia; Ammendolia, Maria Grazia; Fanelli, Incoronata; Minelli, Fabio; Ripabelli, Giancarlo

    2015-03-01

    Listeria monocytogenes virulence depends on the activity of well-characterized virulence factors. In this study, transcription levels of inlA, inlB, hly, bsh and prfA genes in L. monocytogenes strains, and the ability of invasion into CaCo-2 cells were investigated. Serotyping, multiplex-PCR for serovar identification and restriction fragment analysis of inlA were performed. Transcription levels and invasiveness were evaluated by quantitative reverse-transcription PCR and by in vitro assays, respectively. The isolates were of serovars 1/2a, 4b, 1/2c, 1/2b and 3a. Full-length inlA profiles were found for nine of ten clinical isolates, while five of seven cultures from foods showed truncated profile. The analysis of transcription levels of virulence factors encoding genes demonstrated a substantial inter-strain heterogeneity, with clinical strains showing higher levels for almost all genes than isolates from food. A correlation between transcription levels of inlA and inlB, as well as between bsh and prfA, was observed. Significant differences between clinical strains and food isolates in the invasion of CaCo-2 cells were found. Analysis of gene transcription and invasiveness of human cells suggests different virulence phenotypes among L. monocytogenes populations, and this characterization could be a useful tool for risk assessment purposes and for the development of public health strategies. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Anticancer and Antioxidant Activity of Bread Enriched with Broccoli Sprouts

    Science.gov (United States)

    Gawlik-Dziki, Urszula; Świeca, Michał; Dziki, Dariusz; Sęczyk, Łukasz; Złotek, Urszula; Różyło, Renata; Kaszuba, Kinga; Ryszawy, Damian; Czyż, Jarosław

    2014-01-01

    This study is focused on antioxidant and anticancer capacity of bread enriched with broccoli sprouts (BS) in the light of their potential bioaccessibility and bioavailability. Generally, bread supplementation elevated antioxidant potential of product (both nonenzymatic and enzymatic antioxidant capacities); however, the increase was not correlated with the percent of BS. A replacement up to 2% of BS gives satisfactory overall consumers acceptability and desirable elevation of antioxidant potential. High activity was especially found for extracts obtained after simulated digestion, which allows assuming their protective effect for upper gastrointestinal tract; thus, the anticancer activity against human stomach cancer cells (AGS) was evaluated. A prominent cytostatic response paralleled by the inhibition of AGS motility in the presence of potentially mastication-extractable phytochemicals indicates that phenolic compounds of BS retain their biological activity in bread. Importantly, the efficient phenolics concentration was about 12 μM for buffer extract, 13 μM for extracts after digestion in vitro, and 7 μM for extract after absorption in vitro. Our data confirm chemopreventive potential of bread enriched with BS and indicate that BS comprise valuable food supplement for stomach cancer chemoprevention. PMID:25050366

  1. Anticancer and antioxidant activity of bread enriched with broccoli sprouts.

    Science.gov (United States)

    Gawlik-Dziki, Urszula; Świeca, Michał; Dziki, Dariusz; Sęczyk, Łukasz; Złotek, Urszula; Różyło, Renata; Kaszuba, Kinga; Ryszawy, Damian; Czyż, Jarosław

    2014-01-01

    This study is focused on antioxidant and anticancer capacity of bread enriched with broccoli sprouts (BS) in the light of their potential bioaccessibility and bioavailability. Generally, bread supplementation elevated antioxidant potential of product (both nonenzymatic and enzymatic antioxidant capacities); however, the increase was not correlated with the percent of BS. A replacement up to 2% of BS gives satisfactory overall consumers acceptability and desirable elevation of antioxidant potential. High activity was especially found for extracts obtained after simulated digestion, which allows assuming their protective effect for upper gastrointestinal tract; thus, the anticancer activity against human stomach cancer cells (AGS) was evaluated. A prominent cytostatic response paralleled by the inhibition of AGS motility in the presence of potentially mastication-extractable phytochemicals indicates that phenolic compounds of BS retain their biological activity in bread. Importantly, the efficient phenolics concentration was about 12 μM for buffer extract, 13 μM for extracts after digestion in vitro, and 7 μM for extract after absorption in vitro. Our data confirm chemopreventive potential of bread enriched with BS and indicate that BS comprise valuable food supplement for stomach cancer chemoprevention.

  2. Binding and Anticancer Properties of Plumbagin with Human Serum Albumin.

    Science.gov (United States)

    Gou, Yi; Zhang, Yao; Qi, Jinxu; Kong, Linlin; Zhou, Zuping; Liang, Shichu; Yang, Feng; Liang, Hong

    2015-09-01

    Plumbagin has received extensive attention as a promising anticancer drug. Therefore, we investigated the binding and anticancer properties of plumbagin with human serum albumin. Fluorescence results demonstrated that plumbagin interacts with human serum albumin, although its binding affinity may be affected to various extents by different compounds. The human serum albumin-plumbagin complex structure revealed that plumbagin binds to the hydrophobic cavity in the IIA subdomain of human serum albumin through hydrogen bonding and hydrophobic interactions. The plumbagin-human serum albumin complex enhances cytotoxicity by 2- to 3-fold particularly in cancer cells but has no effect on normal cells in vitro. Compared with the unbound drug, the human serum albumin-plumbagin complex promotes HeLa cell apoptosis and has a stronger capacity for cell cycle arrest at the G2/M phase of HeLa cells. In conclusion, this study contributes to the rational design and development of plumbagin-based drugs and a drug-human serum albumin delivery system. © 2014 John Wiley & Sons A/S.

  3. Anticancer and Antioxidant Activity of Bread Enriched with Broccoli Sprouts

    Directory of Open Access Journals (Sweden)

    Urszula Gawlik-Dziki

    2014-01-01

    Full Text Available This study is focused on antioxidant and anticancer capacity of bread enriched with broccoli sprouts (BS in the light of their potential bioaccessibility and bioavailability. Generally, bread supplementation elevated antioxidant potential of product (both nonenzymatic and enzymatic antioxidant capacities; however, the increase was not correlated with the percent of BS. A replacement up to 2% of BS gives satisfactory overall consumers acceptability and desirable elevation of antioxidant potential. High activity was especially found for extracts obtained after simulated digestion, which allows assuming their protective effect for upper gastrointestinal tract; thus, the anticancer activity against human stomach cancer cells (AGS was evaluated. A prominent cytostatic response paralleled by the inhibition of AGS motility in the presence of potentially mastication-extractable phytochemicals indicates that phenolic compounds of BS retain their biological activity in bread. Importantly, the efficient phenolics concentration was about 12 μM for buffer extract, 13 μM for extracts after digestion in vitro, and 7 μM for extract after absorption in vitro. Our data confirm chemopreventive potential of bread enriched with BS and indicate that BS comprise valuable food supplement for stomach cancer chemoprevention.

  4. Genetic Interactions of STAT3 and Anticancer Drug Development

    International Nuclear Information System (INIS)

    Fang, Bingliang

    2014-01-01

    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

  5. T-oligo as an anticancer agent in colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wojdyla, Luke; Stone, Amanda L. [Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, IL (United States); Sethakorn, Nan [Department of Medicine, University of Chicago, Chicago, IL (United States); Uppada, Srijayaprakash B.; Devito, Joseph T. [Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, IL (United States); Bissonnette, Marc [Department of Medicine, University of Chicago, Chicago, IL (United States); Puri, Neelu, E-mail: neelupur@uic.edu [Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, Rockford, IL (United States)

    2014-04-04

    Highlights: • T-oligo induces cell cycle arrest, senescence, apoptosis, and differentiation in CRC. • Treatment with T-oligo downregulates telomere-associated proteins. • T-oligo combined with an EGFR-TKI additively inhibits cellular proliferation. • T-oligo has potential as an effective therapeutic agent for CRC. - Abstract: In the United States, there will be an estimated 96,830 new cases of colorectal cancer (CRC) and 50,310 deaths in 2014. CRC is often detected at late stages of the disease, at which point there is no effective chemotherapy. Thus, there is an urgent need for effective novel therapies that have minimal effects on normal cells. T-oligo, an oligonucleotide homologous to the 3′-telomere overhang, induces potent DNA damage responses in multiple malignant cell types, however, its efficacy in CRC has not been studied. This is the first investigation demonstrating T-oligo-induced anticancer effects in two CRC cell lines, HT-29 and LoVo, which are highly resistant to conventional chemotherapies. In this investigation, we show that T-oligo may mediate its DNA damage responses through the p53/p73 pathway, thereby inhibiting cellular proliferation and inducing apoptosis or senescence. Additionally, upregulation of downstream DNA damage response proteins, including E2F1, p53 or p73, was observed. In LoVo cells, T-oligo induced senescence, decreased clonogenicity, and increased expression of senescence associated proteins p21, p27, and p53. In addition, downregulation of POT1 and TRF2, two components of the shelterin protein complex which protects telomeric ends, was observed. Moreover, we studied the antiproliferative effects of T-oligo in combination with an EGFR tyrosine kinase inhibitor, Gefitinib, which resulted in an additive inhibitory effect on cellular proliferation. Collectively, these data provide evidence that T-oligo alone, or in combination with other molecularly targeted therapies, has potential as an anti-cancer agent in CRC.

  6. T-oligo as an anticancer agent in colorectal cancer

    International Nuclear Information System (INIS)

    Wojdyla, Luke; Stone, Amanda L.; Sethakorn, Nan; Uppada, Srijayaprakash B.; Devito, Joseph T.; Bissonnette, Marc; Puri, Neelu

    2014-01-01

    Highlights: • T-oligo induces cell cycle arrest, senescence, apoptosis, and differentiation in CRC. • Treatment with T-oligo downregulates telomere-associated proteins. • T-oligo combined with an EGFR-TKI additively inhibits cellular proliferation. • T-oligo has potential as an effective therapeutic agent for CRC. - Abstract: In the United States, there will be an estimated 96,830 new cases of colorectal cancer (CRC) and 50,310 deaths in 2014. CRC is often detected at late stages of the disease, at which point there is no effective chemotherapy. Thus, there is an urgent need for effective novel therapies that have minimal effects on normal cells. T-oligo, an oligonucleotide homologous to the 3′-telomere overhang, induces potent DNA damage responses in multiple malignant cell types, however, its efficacy in CRC has not been studied. This is the first investigation demonstrating T-oligo-induced anticancer effects in two CRC cell lines, HT-29 and LoVo, which are highly resistant to conventional chemotherapies. In this investigation, we show that T-oligo may mediate its DNA damage responses through the p53/p73 pathway, thereby inhibiting cellular proliferation and inducing apoptosis or senescence. Additionally, upregulation of downstream DNA damage response proteins, including E2F1, p53 or p73, was observed. In LoVo cells, T-oligo induced senescence, decreased clonogenicity, and increased expression of senescence associated proteins p21, p27, and p53. In addition, downregulation of POT1 and TRF2, two components of the shelterin protein complex which protects telomeric ends, was observed. Moreover, we studied the antiproliferative effects of T-oligo in combination with an EGFR tyrosine kinase inhibitor, Gefitinib, which resulted in an additive inhibitory effect on cellular proliferation. Collectively, these data provide evidence that T-oligo alone, or in combination with other molecularly targeted therapies, has potential as an anti-cancer agent in CRC

  7. Assembly of catalase-based bioconjugates for enhanced anticancer efficiency of photodynamic therapy in vitro.

    Science.gov (United States)

    Zhao, Jie; Fei, Jinbo; Du, Cuiling; Cui, Wei; Ma, Hongchao; Li, Junbai

    2013-11-25

    An oxygen generation core-shell structure uploading rose bengal has been fabricated by covalent assembly of catalase and alginate dialdehyde via Schiff's base. The composite can catalyze the decomposition of intracellular H2O2 to increase the concentration of O2, which effectively enhances the anticancer efficiency of photodynamic therapy in vitro.

  8. The importance of drug metabolites synthesis: the case-study of cardiotoxic anticancer drugs.

    Science.gov (United States)

    Hrynchak, Ivanna; Sousa, Emília; Pinto, Madalena; Costa, Vera Marisa

    2017-05-01

    Anticancer drugs are presently guarantying more survivors as a result of more powerful drugs or combinations of drugs used in therapy. Thus, it has become more crucial to study and overcome the side effects of these therapies. Cardiotoxicity is one of the most relevant side effects on the long-term cancer survivors, because of its high social and economic impact. Drug metabolism can result in active metabolites or toxic metabolites that can lead to important side effects. The metabolites of anticancer drugs are possible culprits of cardiotoxicity; however, the cardiotoxicity of many of the metabolites in several drug classes was not yet suitably studied so far. On the other hand, the use of prodrugs that are bioactivated through metabolism can be a good alternative to obtain more cardio safe drugs. In this review, the methods to obtain and study metabolites are summarized and their application to the study of a group of anticancer drugs with acknowledged cardiotoxicity is highlighted. In this group of drugs, doxorubicin (DOX, 1), mitoxantrone (MTX, 2), cyclophosphamide (CTX, 3) and 5-fluorouracil (5-FU, 4) are included, as well as the tyrosine kinase inhibitors, such as imatinib (5), sunitinib (6) and sorafenib (7). Only with the synthesis and purification of considerable amounts of the metabolites can reliable studies be performed, either in vitro or in vivo that allow accurate conclusions regarding the cardiotoxicity of anticancer drug metabolites and then pharmacological prevention or treatment of the cardiac side effects can be done.

  9. Design, synthesis, characterization and biological studies of ruthenium and gold compounds with anticancer properties

    NARCIS (Netherlands)

    Garza-Ortiz, Ariadna

    2008-01-01

    The design of novel anticancer agents is one of the most active fields in Medicinal Chemistry, as the number of effective drugs for treatment of cancer is still very limited. This demand for new drugs is even higher, considering the high cancer-prevalence rate in our society. The therapeutic

  10. Anti-Cancer Properties of Diethylether Extract of Wood from Sukun ...

    African Journals Online (AJOL)

    Purpose: To evaluate the anti-cancer properties of the diethylether extract of Sukun (Artocarpus altilis) wood. Methods: The extract was tested in human T47D breast cancer cells and examined for its effect on cell viability, nuclear morphology and sub-G1 formation. Cell viability was determined by microculture tetrazolium ...

  11. In Vitro Anticancer Activity of Ethanolic Extract of Euphorbia hirta (L ...

    African Journals Online (AJOL)

    In the present study, In vitro anticancer effects of Euphorbia hirta were investigated. The objectives of this study are to find the presence of secondary metabolites by preliminary phytochemical investigation and FTIR analysis in the Euphorbia hirta. Ethanolic leaf extract of Euphorbia hirta was tested for its cytotoxicity against ...

  12. The chemistry and biology of the anticancer agent, taxol: A review ...

    African Journals Online (AJOL)

    Taxol, is conceivably the single most essential anticancer drug, today. It was first isolated in exceptionally low yield from the bark of the Western Yew, Taxus brevifolia. The clinical effectiveness of Taxol has impelled an incredible endeavor to obtain this intricate molecule synthetically. Owing to the chemical complication of ...

  13. Impedimetric toxicity assay in microfluidics using free and liposome-encapsulated anticancer drugs

    DEFF Research Database (Denmark)

    Caviglia, Claudia; Zor, Kinga; Montini, Lucia

    2015-01-01

    In this work, we have developed a microfluidic cytotoxicity assay for a cell culture and detection platform, which enables both fluid handling and electrochemical/optical detection. The cytotoxic effect of anticancer drugs doxorubicin (DOX), oxaliplatin (OX) as well as OX-loaded liposomes, develo...

  14. Divergent Anticancer Activity of Free and Formulated Camel Milk α-Lactalbumin.

    Science.gov (United States)

    Uversky, Vladimir N; El-Fakharany, Esmail M; Abu-Serie, Marwa M; Almehdar, Hussein A; Redwan, Elrashdy M

    2017-10-21

    Alpha-lactalbumin (α-LA), a small milk calcium-binding globular protein, is known to possess noticeable anticancer activity, which is determined by the ability of this protein to form complexes with oleic acid (OA). To date, in addition to human and bovine α-LA, the ability to form such anti-tumor complexes with OA was described for goat and camel α-LA. Although the mechanisms of the anticancer activity of human and bovine α-LA are already well-studied, little is currently known about the anticancer action of this camel protein. The goal of this study was to fill this gap and to analyze the anticancer and pro-apoptotic activities of camel α-LA in its free form (α-cLA) and as an OA-containing complex (OA-α-cLA) using four human cancer cell lines, including Caco-2 colon cancer cells, PC-3 prostate cancer cells, HepG-2 hepatoma cells, and MCF-7 breast cancer cells as targets. The anti-tumor activities of OA-α-cLA and α-cLA were analyzed using MTT test, annexin/PI staining, cell cycle analysis, nuclear staining, and tyrosine kinase (TK) inhibition methods. We show here that the OA-α-cLA complex does not affect normal cells but has noticeable anti-cancer activity, especially against MCF-7 cells, thus boosting the anticancer activity of α-cLA and improving the selectivity of OA. The OA-α-cLA complex mediated cancer cell death via selective induction of apoptosis and cell-cycle arrest at lower IC 50 than that of free α-cLA by more than two folds. However, OA induced apoptosis at higher extent than OA-α-cLA and α-cLA. OA also caused unselective apoptosis-dependent cell death in both normal and cancer cells to a similar degree. The apoptosis and cell-cycle arresting effect of OA-α-cLA may be attributed to the TK inhibition activity of OA. Therefore, OA-α-cLA serves as efficient anticancer complex with two functional components, α-cLA and OA, possessing different activities. This study declared the effectiveness of OA-α-cLA complex as a promising entity

  15. Actual versus recommended storage temperatures of oral anticancer medicines at patients' homes.

    Science.gov (United States)

    Vlieland, N D; van den Bemt, Bjf; van Riet-Nales, D A; Bouvy, M L; Egberts, Acg; Gardarsdottir, H

    2017-01-01

    Background Substantial quantities of unused medicines are returned by patients to the pharmacy each year. Redispensing these medicines would reduce medicinal waste and health care costs. However, it is not known if medicines are stored by patients as recommended in the product label. Inadequate storage may negatively affect the medicine and reduce clinical efficacy whilst increasing the risk for side effects. Objective To investigate the proportion of patients storing oral anticancer medicines according to the temperature instructions in the product label. Methods Consenting adult patients from six Dutch outpatient hospital pharmacies were included in this study if they used an oral anticancer medicine during February 2014 - January 2015. Home storage temperatures were assessed by inclusion of a temperature logger in the original cancer medicines packaging. The primary outcome was the proportion of patients storing oral anticancer medicines as specified in the Summary of Product Characteristics, either by recalculating the observed temperature fluctuations to a single mean kinetic temperature or by following the temperature instructions taking into account a consecutive 24-h tolerance period. Results Ninety (81.1%) of the 111 included patients (47.8% female, mean age 65.2 (SD: 11.1)) returned their temperature loggers to the pharmacy. None of the patients stored oral anticancer medicines at a mean kinetic temperature above 25℃, one patient stored a medicine requiring storage below 25℃ longer than 24 h above 25℃. None of the patients using medicines requiring storage below 30℃ kept their medicine above 30℃ for a consecutive period of 24 h or longer. Conclusion The majority of patients using oral anticancer medicines store their medicines according to the temperature requirements on the product label claim. Based on our results, most oral anticancer medicines will not be negatively affected by temperature conditions at patients' homes for a maximum of

  16. Investigation of antibacterial and anti-cancer activities of ...

    African Journals Online (AJOL)

    Investigation of antibacterial and anti-cancer activities of Streptomyces sp SRF1 culture filtrate. Kusavadee Sangdee, Benjaporn Buranrat, Prapairat Seephonkai, Nilawan Surapong, Aphidech Sangdee ...

  17. Development of polycationic amphiphilic cyclodextrin nanoparticles for anticancer drug delivery

    Directory of Open Access Journals (Sweden)

    Gamze Varan

    2017-07-01

    Full Text Available Background: Paclitaxel is a potent anticancer drug that is effective against a wide spectrum of cancers. To overcome its bioavailability problems arising from very poor aqueous solubility and tendency to recrystallize upon dilution, paclitaxel is commercially formulated with co-solvents such as Cremophor EL® that are known to cause serious side effects during chemotherapy. Amphiphilic cyclodextrins are favored oligosaccharides as drug delivery systems for anticancer drugs, having the ability to spontaneously form nanoparticles without surfactant or co-solvents. In the past few years, polycationic, amphiphilic cyclodextrins were introduced as effective agents for gene delivery in the form of nanoplexes. In this study, the potential of polycationic, amphiphilic cyclodextrin nanoparticles were evaluated in comparison to non-ionic amphiphilic cyclodextrins and core–shell type cyclodextrin nanoparticles for paclitaxel delivery to breast tumors. Pre-formulation studies were used as a basis for selecting the suitable organic solvent and surfactant concentration for the novel polycationic cyclodextrin nanoparticles. The nanoparticles were then extensively characterized with particle size distribution, polydispersity index, zeta potential, drug loading capacity, in vitro release profiles and cytotoxicity studies.Results: Paclitaxel-loaded cyclodextrin nanoparticles were obtained in the diameter range of 80−125 nm (depending on the nature of the cyclodextrin derivative where the smallest diameter nanoparticles were obtained with polycationic (PC βCDC6. A strong positive charge also helped to increase the loading capacity of the nanoparticles with paclitaxel up to 60%. Interestingly, cyclodextrin nanoparticles were able to stabilize paclitaxel in aqueous solution for 30 days. All blank cyclodextrin nanoparticles were demonstrated to be non-cytotoxic against L929 mouse fibroblast cell line. In addition, paclitaxel-loaded nanoparticles have a

  18. Polyphyllin G exhibits antimicrobial activity and exerts anticancer effects on human oral cancer OECM-1 cells by triggering G2/M cell cycle arrest by inactivating cdc25C-cdc2.

    Science.gov (United States)

    Cai, Xiaoqing; Guo, Lele; Pei, Fei; Chang, Xiaoyun; Zhang, Rui

    2018-04-15

    Plant natural products have long been considered to be important sources of bioactive molecules. A large number of antimicrobial and anticancer agents have been isolated form plants. In the present study we evaluated the antimicrobial and anticancer activity of a plant derived secondery metabolite, Polyphyllin G. The results of antibacterial assays showed that Polyphyllin G prevented the growth of both Gram-positive and Gram-negative bacteria with minimum inhibitory concentrations (MICs) ranging from 13.1 to 78 μg/ml. Antifungal activity measured as inhibition of mycelium growth ranged between 38.32 and 56.50%. Further Polyphyllin G was also evaluated against a panel of cancer cell lines. The IC 50 of Polyphyllin G ranged from 10 to 65 μM. However the IC 50 of Polyphyllin G was found to be comparatively high (120 μM) against the normal FR2 cancer cell line. The lowest IC 50 of 10 μM was found against the oral cancer cell line OECM-1. Therefore further studies were carried out on this cell line only. Our results indicated that Polyphyllin G induced cell arrest in oral cancer OECM-1 cells by inactivation of cdc25C-cdc22 via ATM-Chk 1/2 stimulation. Therefore, we propose that Polyphyllin G might prove a lead molecule in the management of oral cancers and at the same time may prevent the growth of opportunistic microbes. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Contribution of reactive oxygen species to the anticancer activity of aminoalkanol derivatives of xanthone.

    Science.gov (United States)

    Sypniewski, Daniel; Szkaradek, Natalia; Loch, Tomasz; Waszkielewicz, Anna M; Gunia-Krzyżak, Agnieszka; Matczyńska, Daria; Sołtysik, Dagna; Marona, Henryk; Bednarek, Ilona

    2017-11-08

    Reactive oxygen species (ROS) are critically involved in the action of anticancer agents. In this study, we investigated the role of ROS in the anticancer mechanism of new aminoalkanol derivatives of xanthone. Most xanthones used in the study displayed significant pro-oxidant effects similar to those of gambogic acid, one of the most active anticancer xanthones. The pro-oxidant activity of our xanthones was shown both directly (by determination of ROS induction, effects on the levels of intracellular antioxidants, and expression of antioxidant enzymes) and indirectly by demonstrating that the overexpression of manganese superoxide dismutase decreases ROS-mediated cell senescence. We also observed that mitochondrial dysfunction and cellular apoptosis enhancement correlated with xanthone-induced oxidative stress. Finally, we showed that the use of the antioxidant N-acetyl-L-cysteine partly reversed these effects of aminoalkanol xanthones. Our results demonstrated that novel aminoalkanol xanthones mediated their anticancer activity primarily through ROS elevation and enhanced oxidative stress, which led to mitochondrial cell death stimulation; this mechanism was similar to the activity of gambogic acid.

  20. Plant Phenolics: Extraction, Analysis and Their Antioxidant and Anticancer Properties

    Directory of Open Access Journals (Sweden)

    Jin Dai

    2010-10-01

    Full Text Available Phenolics are broadly distributed in the plant kingdom and are the most abundant secondary metabolites of plants. Plant polyphenols have drawn increasing attention due to their potent antioxidant properties and their marked effects in the prevention of various oxidative stress associated diseases such as cancer. In the last few years, the identification and development of phenolic compounds or extracts from different plants has become a major area of health- and medical-related research. This review provides an updated and comprehensive overview on phenolic extraction, purification, analysis and quantification as well as their antioxidant properties. Furthermore, the anticancer effects of phenolics in-vitro and in-vivo animal models are viewed, including recent human intervention studies. Finally, possible mechanisms of action involving antioxidant and pro-oxidant activity as well as interference with cellular functions are discussed.

  1. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

    Directory of Open Access Journals (Sweden)

    Danbo Yang

    2010-12-01

    Full Text Available The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(L-g-glutamylglutamine-paclitaxel nano-conjugate (PGG-PTX. PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic.

  2. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

    International Nuclear Information System (INIS)

    Yang, Danbo; Yu, Lei; Van, Sang

    2010-01-01

    The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(l-γ-glutamylglutamine)-paclitaxel nano-conjugate (PGG-PTX). PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic

  3. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Danbo [Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062 (China); Yu, Lei, E-mail: yu-lei@gg.nitto.co.jp [Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062 (China); Biomedical Group, Nitto Denko Technical Corporation, 501 Via Del Monte, Oceanside, CA 92058 (United States); Van, Sang [Biomedical Group, Nitto Denko Technical Corporation, 501 Via Del Monte, Oceanside, CA 92058 (United States)

    2010-12-23

    The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(l-γ-glutamylglutamine)-paclitaxel nano-conjugate (PGG-PTX). PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic.

  4. Exploiting tumor cell senescence in anticancer therapy

    Science.gov (United States)

    Lee, Minyoung; Lee, Jae-Seon

    2014-01-01

    Cellular senescence is a physiological process of irreversible cell-cycle arrest that contributes to various physiological and pathological processes of aging. Whereas replicative senescence is associated with telomere attrition after repeated cell division, stress-induced premature senescence occurs in response to aberrant oncogenic signaling, oxidative stress, and DNA damage which is independent of telomere dysfunction. Recent evidence indicates that cellular senescence provides a barrier to tumorigenesis and is a determinant of the outcome of cancer treatment. However, the senescence-associated secretory phenotype, which contributes to multiple facets of senescent cancer cells, may influence both cancer-inhibitory and cancer-promoting mechanisms of neighboring cells. Conventional treatments, such as chemo- and radiotherapies, preferentially induce premature senescence instead of apoptosis in the appropriate cellular context. In addition, treatment-induced premature senescence could compensate for resistance to apoptosis via alternative signaling pathways. Therefore, we believe that an intensive effort to understand cancer cell senescence could facilitate the development of novel therapeutic strategies for improving the efficacy of anticancer therapies. This review summarizes the current understanding of molecular mechanisms, functions, and clinical applications of cellular senescence for anticancer therapy. [BMB Reports 2014; 47(2): 51-59] PMID:24411464

  5. Anticancer Phenolics from Dryopteris fragrans (L. Schott

    Directory of Open Access Journals (Sweden)

    Zhen-Dong Liu

    2018-03-01

    Full Text Available Cancer is one of the most major diseases that threatens human health and life. The aim of this work was to obtain novel anticancer molecules from D. fragrans, a kind of medicinal plant. The structure of the new compound was identified using spectroscopic data (1H-NMR, 13C-NMR and two dimensions NMR. Its anticancer properties were evaluated using the 3-(4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2-H-tetrazolium bromide (MTT assay against four human cells including lung cancer cells (A549, breast cancer cells (MCF-7, gastric cancer cells (SGC7901 and noncancerous human umbilical vein endothelial cells (HUVEC. A new phenylpropanoid—(E-caffeic acid-9-O-β-d-xylpyranosyl-(1→2-β-d-glucopyranosyl ester (1, with seven known compounds (2–8—was isolated. The IC50 value of compound 1 against MCF-7 cells was 2.65 ± 0.14 µM, and the IC50 values of compound 8 against three cancer cells were below 20 µM.

  6. Anticancer activity of Ficus religiosa engineered copper oxide nanoparticles.

    Science.gov (United States)

    Sankar, Renu; Maheswari, Ramasamy; Karthik, Selvaraju; Shivashangari, Kanchi Subramanian; Ravikumar, Vilwanathan

    2014-11-01

    The design, synthesis, characterization and application of biologically synthesized nanomaterials have become a vital branch of nanotechnology. There is a budding need to develop a method for environmentally benign metal nanoparticle synthesis, that do not use toxic chemicals in the synthesis protocols to avoid adverse effects in medical applications. Here, it is a report on an eco-friendly process for rapid synthesis of copper oxide nanoparticles using Ficus religiosa leaf extract as reducing and protecting agent. The synthesized copper oxide nanoparticles were confirmed by UV-vis spectrophotometer, absorbance peaks at 285 nm. The copper oxide nanoparticles were analyzed with field emission-scanning electron microscope (FE-SEM), Fourier transform infrared (FT-IR) spectroscopy, dynamic light scattering (DLS) and X-ray diffraction (XRD) spectrum. The FE-SEM and DLS analyses exposed that copper oxide nanoparticles are spherical in shape with an average particle size of 577 nm. FT-IR spectral analysis elucidates the occurrence of biomolecules required for the reduction of copper oxide ions. Zeta potential studies showed that the surface charge of the formed nanoparticles was highly negative. The XRD pattern revealed that synthesized nanoparticles are crystalline in