Submitted to: Molecular Nutrition and Food Research
Publication Type: Peer reviewed journal
Publication Acceptance Date: 6/13/2009
Publication Date: 3/1/2010
Citation: Wang, T.T., Schoene, N.W., Kim, Y.S., Mizuno, C.S., Rimando, A.M. 2010. Differential effects of resveratrol and its methylether analogs on cell cycle and apoptosis in human androgen-responsive LNCaP cancer cells. Molecular Nutrition and Food Research. 54(3):335-344. Interpretive Summary: Population studies support a role for food-derived phytochemicals in prevention of prostate as well as other forms of cancer. Stilbenes are a group of phytochemicals known as phytoalexins that are activated when plants experience stress. These compounds exist in many foods and are widely consumed. Resveratrol is a grape-derived phytoalexin notable for its wide range of health promoting activities including anti-cancer properties. Several other stilbenes structurally similar to resveratrol are also available in food. The biological activities of these compounds remain largely unknown. In the present study we compared the effects of resveratrol and several derivatives for their effects on human prostate cancer cells (LNCaP) in culture. We found that these compounds exert differential effects on LNCaP cell growth and death. Trans-resveratrol trimethylether appeared to be most potent among the compounds tested. These results provide mechanistic information on how these compounds can act to contribute to potential anti-prostate cancer activity. This work provides novel information for the cancer research scientist regarding molecular targets and the mechanism(s) of action of resveratrol and related food derived compounds, and will serve as an important bases for nutrition-based cancer preventive strategies.
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.