Prostate cancer is one of the leading causes of cancer-related deaths. The AR is known to play an important role in cell proliferation and... Show moreProstate cancer is one of the leading causes of cancer-related deaths. The AR is known to play an important role in cell proliferation and cell survival during the development of prostate tumors. Chemical and physical removal of androgens is therefore commonly used to treat prostate cancer. AR regulatory drugs, such as Vorinostat and 17-AAG, are FDA-approved drugs designed to down-regulate AR expression and suppress tumor growth. However, the function of the AR in post-castration tumors is not clear. Recently, our laboratory and others have shown that the AR also has a pro-death function, especially in androgen-independent prostate cancer cells. To determine the function of Vorinostat and 17-AAG on AR expression levels and cell survival in androgen-independent prostate cancer cells, we treated 104-R1 cells, an androgen-independent prostate cancer cell sub-line, with either Vorinostat or 17-AAG. We found that both drugs down-regulated AR protein levels, although Vorinostat was more potent than 17-AAG. Neither drug independently caused significant cell death; however, at certain doses, both drugs induced cell morphological changes that correlated with AR expression levels. Interestingly, Vorinostat synergized with Adriamycin, a commonly used chemotherapeutic drug, to induce cell death, while 17-AAG suppressed Adriamycin-induced apoptosis in 104-R1 cells. These data suggest that the drugs that are effective for androgen-dependent prostate cancer might not be suitable for androgen-independent prostate cancer. M.S. in Biology, December 2012 Show less
