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Cancer Chemopreventive Agent (cancer + chemopreventive_agent)
Selected AbstractsVitamin D and Vitamin D Analogs as Cancer Chemopreventive AgentsNUTRITION REVIEWS, Issue 7 2003DABT, Kathryn Z. Guyton PhD Epidemiologic studies have associated vitamin D, attained through nutrition and sun exposure, with reduced cancer risk. Although dose-limiting hypercalcemia has limited the use of natural vitamin D in cancer prevention, several promising new synthetic vitamin D analogs (deltanoids) are under development. Examples are KH-1060, EB1089, 1 , -hydroxyvitamin D5, vitamin D2, and QW-1624F2-2. Clinical targets for deltanoids include colon, prostate, and breast. Studies to elucidate the molecular mechanisms underlying the observed efficacy of deltanoids are ongoing. The vitamin D receptor, a steroid/thyroid receptor superfamily member, appears to control most deltanoid effects on proliferation, apoptosis, differentiation, and angiogenesis. [source] Endogenous Fluorescence Spectroscopy of Cell Suspensions for Chemopreventive Drug Monitoring,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 1 2005Nathaniel D. Kirkpatrick ABSTRACT Cancer chemopreventive agents such as N -4-(hydroxyphenyl)-retinamide (4HPR) are thought to prevent cancers by suppressing growth or inducing apoptosis in precancerous cells. Mechanisms by which these drugs affect cells are often not known, and the means to monitor their effects is not available. In this study endogenous fluorescence spectroscopy was used to measure metabolic changes in response to treatment with 4HPR in ovarian and bladder cancer cell lines. Fluorescence signals consistent with nicotinamide adenine dinucleotide (NADH), flavin adenine dinucleotide (FAD) and tryptophan were measured to monitor cellular activity through redox status and protein content. Cells were treated with varying concentrations of 4HPR and measured in a stable environment with a sensitive fluorescence spectrometer. Results suggest that redox signal of all cells changed in a similar dose-dependant manner but started at different baseline levels. Redox signal changes depended primarily on changes consistent with NADH fluorescence, whereas the FAD fluorescence remained relatively constant. Similarly, tryptophan fluorescence decreased with increased drug treatment, suggesting a decrease in protein production. Given that each cell line has been shown to have a different apoptotic response to 4HPR, fluorescence redox values along with changes in tryptophan fluorescence may be a response as well as an endpoint marker for chemopreventive drugs. [source] Identifying the differential effects of silymarin constituents on cell growth and cell cycle regulatory molecules in human prostate cancer cellsINTERNATIONAL JOURNAL OF CANCER, Issue 1 2008Gagan Deep Abstract Prostate cancer (PCa) is the leading cause of cancer-related deaths in men; urgent measures are warranted to lower this deadly malignancy. Silymarin is a known cancer chemopreventive agent, but the relative anticancer efficacy of its constituents is still unknown. Here, we compared the efficacy of 7 pure flavonolignan compounds isolated from silymarin, namely silybin A, silybin B, isosilybin A, isosilybin B, silydianin, isosilydianin, silychristin and isosilychristin, in advanced human PCa PC3 cells. Silybin A, silybin B, isosilybin A, isosilybin B, silibinin and silymarin strongly inhibited the colony formation by PC3 cells (p < 0.001), while silydianin, silychristin and isosilychristin had marginal effect (p < 0.05). Using cell growth and death assays, we identified isosilybin B as the most effective isomer. FACS analysis for cell cycle also showed that silybin A, silybin B, isosilybin A, isosilybin B, silibinin and silymarin treatment resulted in strong cell cycle arrest in PC3 cells after 72 hr of treatment, while the effect of silydianin, silychristin and isosilychristin was marginal (if any). Western blot analysis also showed the differential effect of these compounds on the levels of cell cycle regulators-cyclins (D, E, A and B), CDKs (Cdk2, 4 and Cdc2), CDKIs (p21 and p27) and other cell cycle regulators (Skp2, Cdc25A, B, C and Chk2). This study provided further evidence for differential anticancer potential among each silymarin constituent, which would have potential implications in devising better formulations of silymarin against prostate and other cancers. © 2008 Wiley-Liss, Inc. [source] Inhibition of tumour invasion and angiogenesis by epigallocatechin gallate (EGCG), a major component of green teaINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 6 2001Young D. Jung Epidemiological studies have suggested that consumption of green tea may decrease cancer risk. In addition, abundant pre-clinical data from several laboratories have provided convincing evidence that polyphenols present in green tea afford protection against cancer in both in vivo and in vitro studies. Recently, epigallocatechin gallate (EGCG), a putative chemopreventive agent and a major component of green tea, was reported to inhibit tumour invasion and angiogenesis, processes that are essential for tumour growth and metastasis. Understanding the basic principles by which EGCG inhibits tumour invasion and angiogenesis may lead to the development of new therapeutic strategies, in addition to supporting the role of green tea as a cancer chemopreventive agent. [source] The influence of curcumin and manganese complex of curcumin on cadmium-induced oxidative damage and trace elements status in tissues of miceJOURNAL OF APPLIED TOXICOLOGY, Issue 3 2006Vladislav Eybl Abstract Curcumin (diferuoyl methane) from turmeric is a well-known biologically active compound. It has been shown to ameliorate oxidative stress and it is considered to be a potent cancer chemopreventive agent. In our previous study the antioxidative effects of curcumin in cadmium exposed animals were demonstrated. Also manganese exerts protective effects in experimental cadmium intoxication. The present study examined the ability of the manganese complex of curcumin (Mn-curcumin) and curcumin to protect against oxidative damage and changes in trace element status in cadmium-intoxicated male mice. Curcumin or Mn-curcumin were administered at equimolar doses (0.14 mmol/kg b.w.) for 3 days, by gastric gavages, dispersed in methylcellulose. One hour after the last dose of antioxidants, cadmium chloride (33 µmol/kg) was administered subcutaneously. Both curcumin and Mn-curcumin prevented the increase of hepatic lipid peroxidation , expressed as MDA level, induced by cadmium intoxication and attenuated the Cd-induced decrease of hepatic GSH level. No change in hepatic glutathione peroxidase or catalase activities was found in Cd-exposed mice. A decreased GSH-Px activity was measured in curcumin and Mn-curcumin alone treated mice. Neither curcumin nor Mn-curcumin treatment influenced cadmium distribution in the tissues and did not correct the changes in the balance of essential elements caused by Cd-treatment. The treatment with Mn-curcumin increased the Fe and Mn content in the kidneys of both control and Cd-treated mice and Fe and Cu content in the brain of control mice. In conclusion, regarding the antioxidative action, introducing manganese into the curcumin molecule does not potentiate the studied effects of curcumin. Copyright © 2005 John Wiley & Sons, Ltd. [source] Role of mitogen-activated protein kinases in phenethyl isothiocyanate-induced apoptosis in human prostate cancer cellsMOLECULAR CARCINOGENESIS, Issue 3 2005Dong Xiao Abstract The present study was undertaken to examine the role of mitogen-activated protein kinases (MAPKs) in apoptosis induction by phenethyl isothiocyanate (PEITC), a cruciferous vegetable-derived cancer chemopreventive agent, with DU145 and LNCaP human prostate cancer cells as a model. The MAPK family of serine/threonine kinases, including extracellular signal-regulated kinase1/2 (ERK1/2), c- jun N-terminal kinase1/2/3 (JNK1/2/3), and p38 MAPK play an important role in cell proliferation and apoptosis in response to different stimuli. Exposure of DU145 and LNCaP cells to growth suppressive concentrations of PEITC resulted in activation of ERK1/2 and JNKs, but not p38 MAPK, in both cell lines. In DU145 cells, the apoptosis induction by PEITC was statistically significantly attenuated by pharmacological inhibition of JNKs with SP600125. Adenovirus-mediated overexpression of Flag-tagged JNK binding domain (JBD) of JNK-interacting protein-1 (JIP-1), an inhibitor of JNK, also inhibited PEITC-induced apoptosis in DU145 cells. On the other hand, inhibition of ERK1/2 activation with MEK1 inhibitor PD98059 failed to offer protection against PEITC-induced apoptosis in DU145 cells. In LNCaP cells, the PEITC-induced cell death was not affected by either pretreatment with PD98059 or SP600125 or overexpression of JBD of JIP-1. These results indicate that involvement of MAPKs in apoptosis induction by PEITC in human prostate cancer cells is cell line-specific. © 2005 Wiley-Liss, Inc. [source] Allyl isothiocyanate as a cancer chemopreventive phytochemicalMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 1 2010Yuesheng Zhang Abstract Allyl isothiocyanate (AITC), which occurs in many common cruciferous vegetables, is widely and often frequently consumed by humans. Besides antimicrobial activity against a wide spectrum of pathogens, it showed anticancer activity in both cultured cancer cells and animal models, although the underlining mechanisms remain largely undefined. Bioavailability of AITC is extremely high, as nearly 90% of orally administered AITC is absorbed. AITC absorbed in vivo is metabolized mainly through the mercapturic acid pathway and excreted in urine. Available data suggest that urinary concentrations of AITC equivalent are at least ten times higher than in the plasma, and tissue levels of AITC equivalent in the urinary bladder were 14,79 times higher than in other organs after oral AITC administration to rats. These findings suggest that AITC may be most effective in the bladder as a cancer chemopreventive compound. AITC at high-dose levels also exhibit a low degree of cytotoxicity and genotoxicity in animal studies, but such adverse effects are unlikely in humans exposed to dietary levels of AITC. Overall, AITC exhibits many desirable attributes of a cancer chemopreventive agent, and further studies are warranted in order to elucidate its mechanism of action and to assess its protective activity in humans. [source] The modulation of endothelial cell gene expression by green tea polyphenol-EGCGMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 10 2008Liping Liu Abstract Human and animal studies have shown that green tea consumption is associated with a reduced risk of some cancers. This has been attributed to its polyphenol components, in particular (,)-epigallocatechin gallate (EGCG). In addition to be a cancer chemopreventive agent, EGCG inhibits angiogenesis, thus reducing tumor growth and metastasis. We tested EGCG modulation on the gene expression profile of endothelial cells stimulated by VEGF using Affymetrix microarrays. A total of 421 genes were up-regulated and 72 genes were down-regulated at the false discovery rate of 5% by VEGF, EGCG, and EGCG pretreatment followed by VEGF stimulation. The changes in the expression of several pivotal genes were validated by real-time PCR. Furthermore, we have identified two signaling pathways (Wnt and Id) involved in cell proliferation were inhibited by EGCG treatment, suggesting the negative regulation of EGCG on cell proliferation. Our results also indicate that the antiangiogenesis effect of EGCG is partially mediated through its broad inhibition on endothelial cell proliferation. Our data further support earlier observations that the anticancer effect of EGCG is mediated through changes in the expression of genes that are associated with cell proliferation. [source] Anti-Tumor-Initiating Effects of Monascin, an Azaphilonoid Pigment from the Extract of Monascus pilosus Fermented Rice (Red-Mold Rice)CHEMISTRY & BIODIVERSITY, Issue 10 2005Toshihiro Akihisa Monascin (1) constitutes one of the azaphilonoid pigments in the extracts of Monascus pilosus -fermented rice (red-mold rice). Compound 1 was evaluated for its anti-tumor-initiating activity via oral administration on the two-stage carcinogenesis of mouse skin tumor induced by peroxynitrite (ONOO,; PN) or by ultraviolet light B (UVB) as an initiator and 12- O -tetradecanoylphorbol-13-acetate (TPA) as a promoter. Compound 1 exhibited marked inhibitory activity on both PN- and UVB-induced mouse skin carcinogenesis tests. These findings suggest that compound 1 may be valuable as potential cancer chemopreventive agent in chemical and environmental carcinogenesis. [source] Limonoids as cancer chemopreventive agentsJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 3 2006Sohail Ejaz Abstract Nutritional research on the health benefits of substances in plant foods has recently advanced to a new stage. The research frontier has moved from study of classical vitamin deficiency diseases to study of the thousands of phytochemicals that may have important physiological effects. Recent research suggests that citrus fruit consumers may be getting another health benefit from orange juice and other citrus products called limonoids, which appear to possess substantial anticancer activity. Limonoids are highly oxidized triterpenes present in Rutaceae and Maliaceae families. Several citrus limonoids have recently been subjected to anticancer screening utilizing laboratory animals and human breast cancer cells. The experimental results described that citrus limonoids may provide substantial anticancer actions. The compounds have been shown to be free of toxic effects in animal models, so potential exists for the use of limonoids against human cancer in either natural fruits, in citrus fortified with limonoids, or in purified forms of specific limonoids. Although the initial studies are very promising they have been conducted primarily with in vitro cell culture and animal models. Thus, research is needed to determine whether the limonoids may be useful in preventing or treating cancer in humans. Copyright © 2005 Society of Chemical Industry [source] Suppressive effect of inducible nitric oxide synthase (iNOS) expression by the methanol extract of Actinodaphne lancifoliaPHYTOTHERAPY RESEARCH, Issue 10 2004Youngleem Kim Abstract Nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) has played a crucial role in various pathophysiological processes including in,ammation and carcinogenesis. Therefore, the inhibitors of NO synthesis or iNOS gene expression have been considered as potential anti-in,ammatory and cancer chemopreventive agents. In our continuous search for iNOS inhibitors from natural products we have evaluated indigenous Korean plant extracts using an assay for inhibition of nitric oxide formation on lipopolysaccharide (LPS)-activated mouse macrophage RAW 264.7 cells. As a result, the methanolic stem extract of Actinodaphne lancifolia showed an inhibitory activity of NO production in a dose-dependent manner (IC50 = 2.5 µg/ml). Additional study demonstrated that the extract of Actinodaphne lancifolia signi,cantly suppressed the iNOS protein and gene expression in a dose-dependent manner. These results suggest that Actinodaphne lancifolia could be a potential candidate for developing an iNOS inhibitor from natural products. Further elucidation of active principles for development of new cancer chemopreventive and/or anti-in,ammatory agents could be warranted. Copyright © 2004 John Wiley & Sons, Ltd. [source] Chemistry and antioxidative factors in rosemary and sageBIOFACTORS, Issue 1-4 2000Chi-Tang Ho Rosemary and sage are common spices used in food. In our recent search of cancer chemopreventive agents from spices, the alcohol extracts of rosemary and sage showed strong antumorigenic activities. Rosemary and sage extracts contain active antioxidative factors such as phenolic diterpenes, flavonoids and phenolic acids. Here we discuss chromatographic methods used to separate and purify compounds from these spices and MS and NMR spectrometry to identify the isolated compounds. Several new compounds isolated from sage were determined to be 6-O-caffeoyl-,-D-fructofuranosyl-(2 , 1)-,-glucopyranoside, 1-O-caffeoyl-,-D-apiofuranosyl-(1 , 6)-,-D-glucopyranoside, 1-O-p-hydroxybenzoyl-,-D-apiofuranosyl-(1 , 6)-,-D-glucopyranoside, 1-O-(3-methyl-2,3,4-trihydroxybutyl)-6-O-feruloyl-,-D-glucopyranoside, 4-hydroxyacetophenone 4-O-[5-O-(3,5-dimethoxy-4-hydroxybenzoyl)-,-D-apiofrunosyl]-(1 , 2)-,-D-glucopyranoside and 1-O-[2-hydroxy-5-(2-hydroxyethyl)phenyl]-6-O-trans-caffeoyl-,-D-glucopyranoside. [source] | ||||||||||||||||