Background: The transhydroxystilbene resveratrol is found at high levels in red wine and grapes, and red wine consumption may be inversely associated with prostate cancer risk. It is thought to play a protective role against cancer by inducing changes in cell cycle, inhibition of proliferation, prevention of oxidative DNA damage and induction of apoptosis. To gain insights into the possible mechanisms of action of resveratrol in human prostate cancer, we performed DNA microarray analysis of the temporal transcriptional program induced by treatment of the human prostate cancer cell line LNCaP with resveratrol. Methods: Spotted DNA microarrays containing over 42,000 elements were used to obtain a global view of the effects of resveratrol on gene expression. Prostate specific antigen (PSA) and androgen receptor (AR) expression were determined by Northern and immunoblot analyses. Cell cycle distribution and proliferation was assessed by flow cytometry. Results: We observed time-dependent expression changes in more than 1600 transcripts as early as 6 hours after treatment with resveratrol. Most striking was the modulation of a number of important genes in the androgen axis including PSA and AR. Resveratrol also down-regulated expression of 442 cell cycle and proliferation specific genes involved in all phases of the cell cycle, induced negative regulators of proliferation, and caused accumulation of cells at the S and G2/M phases. Furthermore, resveratrol induced transcripts involved in apoptosis and those encoding carcinogen defense (phase 2) enzymes. Conclusions: Resveratrol produces gene expression changes in the androgen axis, cell cycle regulators, and phase 2 enzymes that may underlie its anticancer activities in prostate cancer. Sunita B. Jones, Samuel E. DePrimo, James D. Brooks. Presented at AACR Frontiers in Cancer Prevention Research, 2003.