Technical Abstract: Stilbenes are a group of phytochemicals known as phytoalexins that become activated when plants are stressed. These compounds exist in many foods and are widely consumed. Resveratrol is a grape-derived phytoalexin notable for a wide range of health promoting activities, including anti-cancer properties. Several other stilbenes structurally similar to resveratrol are also available in food, but their biological activities remain largely unknown. To fully realize the anti-cancer efficacy of these compounds, it would be important to first characterize molecular events that follow the treatment of cells. In the present study, we compared the effects of resveratrol and its natural derivatives petrostibene, trans-resveratrol trimethylether, trans-pinostilbene, and trans-desoxyrhapontigenin on androgen responsive human prostate cancer LNCaP cells. We found that these compounds exert differential effects on LNCaP cell growth, cell cycle, and apoptosis. Trans-resveratrol trimethylether appeared to be the most potent compound among the stilbenes tested. Treatment of LNCaP cells with trans-resveratrol trimethylether resulted in G2/M blockage while other compounds, including resveratrol, induced G1/S arrest. Moreover, different from other compounds, trans-resveratrol trimethylether induced apoptosis. At the molecular level, the effects of these compounds on cell cycle correlated with the induction of mRNA levels for the cyclin-dependent kinase inhibitor 1A and B. In addition, these compounds also inhibited both androgen- and estrogen-mediated pathways. These results provide mechanistic information on how resveratrol and its methylether analogs contribute to potential anti-prostate cancer activity.