DNA Microarray in Nutrigenomics and Cancer Prevention Research: Elucidating Molecular Signatures of Cancer Preventive Phytochemicals

Abstract

Population studies support an important role for diet in prevention of chronic diseases such as cancer. Several questions remain to be elucidated including the identity of active components in the diet, their molecular targets, and the mechanisms of action. Global gene expression microarray technology was used in a cell culture model to address these questions and understand the potential interaction of diet-derived compounds with cellular targets and their pathways. Our studies on the cancer protective phytochemical resveratrol will be described as an example of this approach. Resveratrol is a phytochemical studied as a prostate cancer chemopreventive agent; however, its efficacy and mechanism of action remain largely unknown. We found that resveratrol inhibited cell growth in cultured LNCaP cells, and that the growth inhibitory effects appeared through modulation of both androgen- and estrogen-mediated events. Microarray analysis identified a group of androgen-responsive genes in LNCaP cells that were broadly affected by resveratrol in vitro. The effect of resveratrol on expression of these genes appeared to be through inhibition of both androgen- and estrogen-mediated transcription. In an in vivo xenograft model, resveratrol delayed LNCaP tumor growth and inhibited expression of a marker for steroid hormone responses; however, it also led to increased angiogenesis and inhibition of apoptosis in the xenograft.