Woo K J, Yoo Y H, Park J-W, Kwon T K
Department of Immunology, School of Medicine, Keimyung University, 194 DongSan-Dong Jung-Gu, Taegu 700-712, Korea.
Apoptosis. 2005 Dec;10(6):1333-43. doi: 10.1007/s10495-005-2763-5.
Aberrant overexpression of antiapoptotic members of the Bcl-2 protein family contributes to resistance to anticancer therapeutic drugs. Thus, this protein represent attractive target for novel anticancer agents. In the present study, we determined the effect of the anti-apoptosis protein Bcl-2 on caspase-3 activation, PLC-gamma1 degradation and Akt activation during the various anticancer agents-induced apoptosis. Treatment with chrysin for 12 h produced morphological features of apoptosis in U937 cells, which was associated with caspase-3 activation and PLC-gamma1 degradation. Induction of apoptosis was also accompanied by down-regulation of XIAP and inactivation of Akt. Chrysin-induced caspase-3 activation, PLC-gamma1 degradation and apoptosis were significantly attenuated in Bcl-2 overexpressing U937/Bcl-2 cells. Ectopic expression of Bcl-2 appeared to inhibit ceramide-, and Akt specific inhibitor (SH-6)-induced apoptosis by sustained Akt activation. Thus, our findings imply that some of the biological functions of Bcl-2 may be attributed to their ability to inhibit anticancer agents-induced apoptosis through the sustained Akt activation.
Bcl-2蛋白家族抗凋亡成员的异常过表达导致对抗癌治疗药物产生抗性。因此，这种蛋白质是新型抗癌药物的有吸引力的靶点。在本研究中，我们确定了抗凋亡蛋白Bcl-2在各种抗癌药物诱导的细胞凋亡过程中对caspase-3激活、PLC-γ1降解和Akt激活的影响。用白杨素处理12小时可使U937细胞产生凋亡的形态学特征，这与caspase-3激活和PLC-γ1降解有关。细胞凋亡的诱导还伴随着XIAP的下调和Akt的失活。在过表达Bcl-2的U937/Bcl-2细胞中，白杨素诱导的caspase-3激活、PLC-γ1降解和细胞凋亡明显减弱。Bcl-2的异位表达似乎通过持续激活Akt来抑制神经酰胺和Akt特异性抑制剂（SH-6）诱导的细胞凋亡。因此，我们的研究结果表明，Bcl-2的一些生物学功能可能归因于它们通过持续激活Akt来抑制抗癌药物诱导的细胞凋亡的能力。
