title: Resveratrol potentiates grape seed extract induced human colon cancer cell apoptosis.
abstract: 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.
authors.affiliation: Department of Food Science and Human Nutrition, Colorado State University, Fort Collins, Colorado 80523-1571, USA.
authors.forename: Sridhar
authors.initials: S
authors.lastname: Radhakrishnan
authors.forename: Lavanya
authors.initials: L
authors.lastname: Reddivari
authors.forename: Robert
authors.initials: R
authors.lastname: Sclafani
authors.forename: Undurti N
authors.initials: UN
authors.lastname: Das
authors.forename: Jairam
authors.initials: J
authors.lastname: Vanamala
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002469:Cell Separation; D002853:Chromatography, Liquid; D003110:Colonic Neoplasms / Q000473:pathology*; D005434:Flow Cytometry; D006801:Humans; D013058:Mass Spectrometry; D010936:Plant Extracts / Q000494:pharmacology*; D000077185:Resveratrol; D012639:Seeds / Q000737:chemistry*; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D010936:Plant Extracts; D013267:Stilbenes; D000077185:Resveratrol