Suppression of Human Prostate Cancer Cell Growth By α1-Adrenoceptor Antagonists Doxazosin and Terazosin via Induction of Apoptosis

摘要: Recent evidence from our laboratory has demonstrated that alpha1-adrenoceptor antagonists doxazosin and terazosin induced apoptosis in prostate epithelial smooth muscle cells patients with benign prostatic hypertrophy (BPH; J. Urol., 159: 1810-1815, 1998; 161: 2002-2007, 1999). In this study, we investigated the biological action of three antagonists, doxazosin, terazosin, tamsulosin, against cancer cell growth. The antigrowth effect was examined two human lines, PC-3 DU-145, a primary culture, SMC-1, on basis of: (a) viability assay; (b) rate DNA synthesis; (c) induction apoptosis. Our results indicate treatment or significant loss viability, via dose-dependent manner, whereas tamsulosin had no Neither nor exerted proliferation cells. Exposure to phenoxybenzamine, an irreversible inhibitor alpha1-adrenoceptors, does not abrogate apoptotic This suggests activity is independent their capacity antagonize alpha1-adrenoceptors. Furthermore, vivo efficacy trial administration (at tolerated pharmacologically relevant doses) SCID mice bearing xenografts resulted inhibition tumor These findings demonstrate ability (but tamsulosin) suppress growth vitro by inducing without affecting proliferation. provides rationale for targeting both drugs, already clinical use established adverse-effect profiles, tumors advanced cancer.