Bcl-2 oncoprotein protects the human prostatic carcinoma cell line PC3 from TRAIL-mediated apoptosis

The role of Bcl-2 in TRAIL-induced apoptosis has been investigated in lymph oid cells, Here we show that the human prostatic carcinoma cell line PC3 wa s sensitive to TRAIL treatment whereas PC3 overexpressing of Bcl-2 was resi stant. TRAIL receptors ligation in PC3 activated caspases -2, -3, -7, -8, a nd -9, induced Bid processing, dissipation of mitochondrial transmembrane p otential (Delta Psi (m)), and cytochrome c release. We have detected caspas es -8 and -3 only in the cytosolic fraction of cells, but caspases -2, -7, and -9 were found both in cytosolic and mitochondrial fractions. Bcl-2 over expression did not affect caspase-8 activation although it did change the p rocessing pattern of caspase-3, At the same time, Bcl-2 overexpression inhi bited the activation of mitochondrial localized caspases -2, -7, and -9, Bc l-2 also abrogated TRAIL-induced cytochrome c release and dissipation of De lta Psi (m). These findings suggest that TRAIL-induced apoptosis in the epi thelial cell line PC3 depends both on mitochondrial integrity and caspase a ctivation.