Resveratrol potentiates grape seed extract induced human colon cancer cell apoptosis. 2011

Sridhar Radhakrishnan, and Lavanya Reddivari, and Robert Sclafani, and Undurti N Das, and Jairam Vanamala
Department of Food Science and Human Nutrition, Colorado State University, Fort Collins, Colorado 80523-1571, USA.

Colon cancer is the third leading cause of cancer deaths in men and women. Grape seed extract (GSE) and resveratrol (RSV) are potent chemopreventive agents against colon cancer both in vitro and in vivo, at relatively high concentrations. We hypothesized that RSV and GSE may act in concert with each other in potentiating their anti-cancer properties at sub-optimal doses, because they occur as complex mixtures in grapes. In this study, we showed that RSV (~25 micromolar) potentiated GSE (≤ 35 microg/mL) induced colon cancer cell apoptosis via activation of p53 dependent pathways. Elevation of apoptosis was much more pronounced in p53 +/+ cells compared to p53 -/- cells. Apoptosis was strongly correlated with pp53 levels and Bax:Bcl-2 ratio, key players in the mitochondrial apoptotic pathway. Caspase-3 inhibition and reactive oxygen species suppression attenuated apoptosis induced by the combination. RSV-GSE combination suppressed proliferation and induced apoptosis even in the presence of mitogenic growth factor IGF-1, suggesting the importance of understanding the potentiating effects of phytonutrients in combination as they would occur in nature rather than individually.

UI MeSH Term Description Entries
D010936 Plant Extracts Concentrated pharmaceutical preparations of plants obtained by removing active constituents with a suitable solvent, which is evaporated away, and adjusting the residue to a prescribed standard. Herbal Medicines,Plant Extract,Extract, Plant,Extracts, Plant,Medicines, Herbal
D002469 Cell Separation Techniques for separating distinct populations of cells. Cell Isolation,Cell Segregation,Isolation, Cell,Cell Isolations,Cell Segregations,Cell Separations,Isolations, Cell,Segregation, Cell,Segregations, Cell,Separation, Cell,Separations, Cell
D002853 Chromatography, Liquid Chromatographic techniques in which the mobile phase is a liquid. Liquid Chromatography
D003110 Colonic Neoplasms Tumors or cancer of the COLON. Cancer of Colon,Colon Adenocarcinoma,Colon Cancer,Cancer of the Colon,Colon Neoplasms,Colonic Cancer,Neoplasms, Colonic,Adenocarcinoma, Colon,Adenocarcinomas, Colon,Cancer, Colon,Cancer, Colonic,Cancers, Colon,Cancers, Colonic,Colon Adenocarcinomas,Colon Cancers,Colon Neoplasm,Colonic Cancers,Colonic Neoplasm,Neoplasm, Colon,Neoplasm, Colonic,Neoplasms, Colon
D005434 Flow Cytometry Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. Cytofluorometry, Flow,Cytometry, Flow,Flow Microfluorimetry,Fluorescence-Activated Cell Sorting,Microfluorometry, Flow,Cell Sorting, Fluorescence-Activated,Cell Sortings, Fluorescence-Activated,Cytofluorometries, Flow,Cytometries, Flow,Flow Cytofluorometries,Flow Cytofluorometry,Flow Cytometries,Flow Microfluorometries,Flow Microfluorometry,Fluorescence Activated Cell Sorting,Fluorescence-Activated Cell Sortings,Microfluorimetry, Flow,Microfluorometries, Flow,Sorting, Fluorescence-Activated Cell,Sortings, Fluorescence-Activated Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077185 Resveratrol A stilbene and non-flavonoid polyphenol produced by various plants including grapes and blueberries. It has anti-oxidant, anti-inflammatory, cardioprotective, anti-mutagenic, and anti-carcinogenic properties. It also inhibits platelet aggregation and the activity of several DNA HELICASES in vitro. 3,4',5-Stilbenetriol,3,4',5-Trihydroxystilbene,3,5,4'-Trihydroxystilbene,Resveratrol, (Z)-,Resveratrol-3-sulfate,SRT 501,SRT-501,SRT501,cis-Resveratrol,trans-Resveratrol,trans-Resveratrol-3-O-sulfate,Resveratrol 3 sulfate,cis Resveratrol,trans Resveratrol,trans Resveratrol 3 O sulfate
D012639 Seeds The encapsulated embryos of flowering plants. They are used as is or for animal feed because of the high content of concentrated nutrients like starches, proteins, and fats. Rapeseed, cottonseed, and sunflower seed are also produced for the oils (fats) they yield. Diaspores,Elaiosomes,Embryos, Plant,Plant Embryos,Plant Zygotes,Zygotes, Plant,Diaspore,Elaiosome,Embryo, Plant,Plant Embryo,Plant Zygote,Seed,Zygote, Plant
D013058 Mass Spectrometry An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers. Mass Spectroscopy,Spectrometry, Mass,Spectroscopy, Mass,Spectrum Analysis, Mass,Analysis, Mass Spectrum,Mass Spectrum Analysis,Analyses, Mass Spectrum,Mass Spectrum Analyses,Spectrum Analyses, Mass
D013267 Stilbenes Organic compounds that contain 1,2-diphenylethylene as a functional group. Stilbene,Stilbene Derivative,Stilbene Derivatives,Stilbenoid,Stilbenoids,Derivative, Stilbene,Derivatives, Stilbene

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