Prostate cancer is the second leading cause of
cancer-related death in men. Treatment failure in
prostate cancer is usually due to the development of
androgen independence and resistance to chemotherapeutic drugs at an advanced stage. Recently, it was reported that the alpha1-adrenoceptor antagonist
terazosin was able to inhibit
prostate cancer cell growth and indicated that it may have an implication in the treatment of
prostate cancer. The aim of the present study was to investigate the mechanisms involved in
terazosin-induced
prostate cancer cell death using two
androgen-independent cell lines, PC-3 and DU145. Our results showed that
terazosin inhibited not only
prostate cancer cell growth but also colony forming ability, which is the main target of
chemotherapy. We also found that the sensitivity of these cells to
terazosin was not affected by the presence of either functional p53 or Rb, suggesting that the
terazosin-induced cell death was independent of p53 and Rb. However, the
terazosin-induced cell death was associated with G1 phase cell cycle arrest and up-regulation of p27KIP1. In addition, up-regulation of Bax and down-regulation of Bcl-2 was also observed indicating that these two apoptotic regulators may play important roles in
terazosin-mediated cell death pathway. Our results provide evidence for the first time that
terazosin may have a therapeutic potential in the treatment of advanced
prostate cancer.