TRAIL (APO-2L) induces apoptosis in human prostate cancer cells that is inhibitable by Bcl-2

To determine if TRAIL-induced apoptosis in human prostate tumor cells was s uppressed by bcl-2, we compared the levels of apoptosis induced by recombin ant human TRAIL in pairs of isogenic cell lines that do or do not express b cl-2, Three human prostate tumor cell lines (PC3, DU145 and LNCaP) and thei r bcl-2-expressing counterparts were tested for their susceptibility to TRA IL, Cells were exposed to TRAIL in the presence of cycloheximide which acte d as a sensitizer. Apoptosis was induced rapidly in PC3 and DU145 neo-contr ol transfected cells, whereas induction in LNCaP required 24 h, All three c ell line variants expressing bcl-2 were resistant to the apoptotic effects of TRAIL. Caspase 3 and 8 activation was also detected in the neo control c ells after treatment with TRAIL, demonstrating the rapid activation of the caspase cascade similar to that seen with other death receptors, Bcl-2 over expression in these cells blocked activation of these caspases, suggesting that bcl-2 expression of human cancer cells may be a critical factor in the therapeutic efficacy of TRAIL.