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Carcinogenesis, Vol. 22, No. 10, 1633-1639, October 2001
© 2001 Oxford University Press


CANCER BIOLOGY

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

Jong-Wook Park, Yun-Jung Choi, Seong-Il Suh1,, Won-Ki Baek1,, Min-Ho Suh1,, Ing-Nyol Jin2,, Do Sik Min3,, Ju-Hyung Woo, Jong-Soo Chang4,, Antonino Passaniti6,, Young Han Lee5, and Taeg Kyu Kwon,7

Department of Immunology,
1 Department of Microbiology, School of Medicine, Keimyung University, 194 DongSan-Dong Jung-Gu, Taegu, 700-712,
2 Department of Microbiology, College of Natural Sciences, Kyungpook University, Taegu,
3 Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul, 137-701,
4 Department of Life Science, Daejin University, Pochon-gun, Kyeonggido,
5 Department of Biochemistry, College of Medicine, Yeungnam University, Taegu, South Korea and
6 Department of Pathology, Greenebaum Cancer Center, University of Maryland Baltimore, Maryland, USA

Resveratrol has been shown to induce anti-proliferation and apoptosis of human cancer cell lines. In the present study, we determined the effect of high intracellular levels of the anti-apoptosis protein Bcl-2 on caspase-3 activation, PLC-{gamma}1 degradation and cytochrome c release during resveratrol-induced apoptosis. For this, we used U937/vector and U937/Bcl-2 cells, which were generated by transfection of the cDNA of the Bcl-2 gene. As compared with U937/vector, U937/Bcl-2 cells exhibited a 4-fold greater expression of Bcl-2. Treatment with 60 or 100 µM resveratrol for 24 h produced morphological features of apoptosis and DNA fragmentation in U937/vector cells, respectively. This was associated with caspase-3 activation and PLC-{gamma}1 degradation. In contrast, resveratrol-induced caspase-3 activation and PLC-{gamma}1 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 resveratrol-induced apoptosis by a mechanism that interferes with cytochrome c release and activity of caspase-3 that is involved in the execution of apoptosis.


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