Although significant improvements in early detection and treatment for prostate cancer have been made in the recent years, there are 190,000 newly diagnosed prostate cancer in the U. S. each year. It has been suggested that chemoprevention could be one of most effective ways for combating prostate cancer. Plant phenols are regular constituents of plant foods in human diets. Some of these compounds may have anti-cancer activities that may be useful for prostate cancer prevention. Our preliminary studies clearly showed that selected plant phenols have potent inhibitory effects on the expression and function of the androgen receptor (AR) and other regulatory factors. Androgens/androgen receptor (AR) are important risk factors for prostate cancer development. We hypothesize that tea plant phenols may play a role in repressing the development of prostate cancer by inhibiting the expression and function of the AR and other relevant genes. In this proposal, we will study the molecular mechanism by which plant phenols such as tea polyphenols affect the regulation of expression of the AR gene in prostate cells. Northern, western, and in vitro DNA-protein interaction assays as well as gene transfer experiments will be used to study the effects of tea phenols on the expression of the AR. One major goal of this proposal is to identify polyphenol responsive regulatory factors that influence the expression of AR. A recently developed transgenic mouse prostate cancer model will be used to study preventive effect of plant phenols on prostate cancer that is driven initially by androgens. It is expected this study will provide a solid and in-depth molecular basis for the potential role of plant phenols to inhibit the promotion and development of prostate cancer in humans.
