Bcl-2 overexpression attenuates resveratrol-induced apoptosis in U937 cells by inhibition of caspase-3 activity

Resveratrol has been shown to induce anti-proliferation and apoptosis of hu man cancer cell lines. In the present study, we determined the effect of hi gh intracellular levels of the anti-apoptosis protein Bcl-2 on caspase-3 ac tivation, PLC-gamma1 degradation and cytochrome c release during resveratro l-induced apoptosis. For this, we used U937/vector and U937/Bcl-2 cells, wh ich were generated by transfection of the cDNA of the Bcl-2 gene. As compar ed with U937/vector, U937/Bcl-2 cells exhibited a 4-fold greater expression of Bcl-2. Treatment with 60 or 100 muM resveratrol for 24 h produced morph ological features of apoptosis and DNA fragmentation in U937/vector cells, respectively. This was associated with caspase-3 activation and PLC-gamma1 degradation. In contrast, resveratrol-induced caspase-3 activation and PLC- gamma1 degradation and apoptosis were significantly inhibited in U937/Bcl-2 cells. Bcl-2 overexpressing cells exhibited less cytochrome c release and sustained expression levels of the IAP proteins during resveratrol-induced apoptosis. In addition, these findings indicate that Bcl-2 inhibits resvera trol-induced apoptosis by a mechanism that interferes with cytochrome c rel ease and activity of caspase-3 that is involved in the execution of apoptos is.