Effects of alpha(1)-adrenoceptor (alpha(1)-AR) antagonists on cell proliferation and apoptosis in the prostate: Therapeutic implications in prostaticdisease

BACKGROUND. Benign prostate hyperplasia (BPH) and prostate cancer establish ed that disruption of the molecular mechanisms that regulate apoptosis and cell proliferation among the stromal and epithelial cell populations, may u nderlie the neoplastic development that characterizes the aging gland. This work examined the effects of selected alpha(1)-adrenoceptor (alpha (1)-AR) antagonists (blockers) on cellular dynamics to determine whether induction of apoptosis or inhibition of proliferation could contribute to the overal l clinical profile. METHODS. Our efforts were focused on investigating whether alpha (1)-AR ant agonists of two different chemical classes affect prostate pathophysiology via mechanisms other than smooth muscle contraction. In in vitro experiment s, the two clinically used quinazoline alpha (1)-adrenoceptor antagonists t erazosin and doxazosin and the chemically-distinct sulphonamide, tamsulosin , were examined for effects on prostatic tumor growth, by inhibiting cell p roliferation and/or inducing apoptosis. RESULTS. Our findings suggest that alpha (1)-AR antagonists, terazosin and doxazosin, suppress prostatic growth by inducing apoptosis in a dose-depend ent manner and without affecting cell proliferation. Tamsulosin exerted no effect on prostate cancer cell growth. The apoptotic effect of terazosin an d doxazosin appears to be independent of the alpha (1)-adrenoceptor block. CONCLUSIONS. Taken together, our findings demonstrate the ability of the qu inazoline alpha-blockers, terazosin and doxazosin, but not the sulphonamide , tamsulosin, to suppress prostate growth by inducing apoptosis among the e pithelial cells in the benign and malignant prostate. These studies underwr ite the durability of the response seen in long-term studies with terazosin , and suggest the potential of this drug in the treatment of prostate carci noma. Prostate Supplement 9:42-46, 2000. (C) 2000 Wiley-Liss, Inc.