Quercetin inhibits the expression and function of the androgen receptor inLNCaP prostate cancer cells

The androgen receptor (AR) is involved in the development and progression o f prostate cancer. In order to find new compounds that may present novel me chanisms to attenuate the function of AR, we investigated the effect of a n atural flavonoid chemical, quercetin, on androgen action in an androgen-res ponsive LNCaP prostate cancer cell line. Western blot analysis showed that AR protein expression was inhibited by quercetin in a dose-dependent manner . To demonstrate that the repression effects on AR expression can actually reduce its function, we found that quercetin inhibited the secretion of the prostate-specific, androgen-regulated tumor markers, PSA and hK2, The mRNA levels of androgen-regulated genes such as PSA, NKX3.1 as well as ornithin e decarboxylase (ODC) were down-regulated by quercetin. Transient transfect ions further showed that quercetin inhibited AR-mediated PSA expression at the transcription level. Finally, it was demonstrated that quercetin could repress the expression of the AR gene at the transcription level. Our resul t suggests that quercetin can attenuate the function of AR by repressing it s expression and has the potential to become a chemopreventive and/or chemo therapeutic agent for prostate cancer.