Mechanism of Selenium Chemoprevention and Therapy in Prostate Cancer

摘要

The goal of this application is to elucidate the importance of down regulation of AR signaling by multiple selenium compounds and select the best leading selenium compound for prostate cancer chemoprevention and therapy. In this application, we will further study the mechanisms of AR downregulation by multiple selenium compounds and functional significance of this down regulation in prostate cancer chemoprevention and therapy. Prevention trials demonstrated that selenium reduced prostate cancer incidence by 50%, establishing selenium as a promising chemopreventive agent for prostate cancer. Selenium inhibited human prostate cancer cell growth, blocked cell cycle progression at multiple transition points, and induced apoptotic cell death. We have demonstrated a novel mechanism of selenium anticancer action in which selenium markedly reduces androgen receptor (AR) expression and AR-mediated gene expression including prostate-specific antigen (PSA) in human prostate cancer cells in vitro and in vivo. Androgen signaling through androgen receptor (AR) plays an important role not only in maintaining the function of the prostate, but also in promoting the development of androgen-independent prostate cancer. AR signaling is often hyperactive in androgen-independent prostate cancer.