Tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in androgen-independent prostate cancer cells.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been reported to induce cell death in a variety of transformed cells but spared the normal cells. In this study, we examined its potential against advanced prostate cancer cells. Treatment of PC-3 and DU145 cells with TRAIL caused a rapid apoptotic cell death, whereas tumor necrosis factor-alpha (TNF-alpha) is ineffective unless in the presence of the protein synthesis inhibitor cycloheximide. The induction of apoptosis by TRAIL in PC-3 cells was mediated by a death receptor, DR 4, and the downstream caspases. Treatment of PC-3 cells with TRAIL also activated c-Jun NH2-terminal kinase 1 (JNK1); however, inhibition of JNK1 activation by its dominant-negative mutant had little effect on TRAIL-induced apoptosis. Furthermore, TRAIL weakly stimulated nuclear factor kappaB activity in PC-3 cells. Interestingly, activation of nuclear factor kappaB pathway by pretreatment with TNF-alpha did not prevent the induction of apoptosis by TRAIL. These data indicate that TRAIL triggers apoptosis in advanced prostate cancer cells through the activation of caspase cascades, which appears to be independent of TNF-alpha- and JNK-mediated mechanisms.