Bax is essential for mitochondrion-mediated apoptosis but not for cell death caused by photodynamic therapy

被引:76
作者
Chiu, SM
Xue, LY
Usuda, J
Azizuddin, K
Oleinick, NL
机构
[1] Case Western Reserve Univ, Sch Med BRB324, Dept Radiat Oncol, Cleveland, OH 44106 USA
[2] Case Western Reserve Univ, Sch Med BRB324, CWRU, Ireland Comprehens Canc Ctr, Cleveland, OH 44106 USA
关键词
photodynamic therapy; phthalocyanine Pc 4; Bax; apoptosis; cell death;
D O I
10.1038/sj.bjc.6601298
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The role of Bax in the release of cytochrome c from mitochondria and the induction of apoptosis has been demonstrated in many systems. Using immunocytochemical staining, we observed that photodynamic therapy (PDT) with the photosensitiser Pc 4 induced Bax translocation from the cytosol to mitochondria, and the release of cytochrome c from mitochondria as early signalling for the intrinsic pathway of apoptosis in human breast cancer MCF-7c3 cells. To test the role of Bax in apoptosis, MCF-7c3 cells were treated with Bax antisense oligonucleotides, which resulted in as much as a 50% inhibition of PDT-induced apoptosis. In the second approach, Bax-negative human prostate cancer DU-145 cells were studied. Following PDT, the hallmarks of apoptosis, including the release of cytochrome c from mitochondria, loss of mitochondrial membrane potential, caspase activation, and chromatin condensation and fragmentation, were completely blocked in these cells. Restoration of Bax expression in DU-145 cells restored apoptosis, indicating that the resistance of DU-145 cells to PDT-induced apoptosis is due to the lack of Bax rather than to another defect in the apoptotic machinery. However, despite the inhibition of apoptosis, the Bax-negative DU-145 cells were as photosensitive as Bax-replete MCF-7c3 cells, as determined by clonogenic assay. Thus, for Pc 4-PDT, the commitment to cell death occurs prior to Bax activation.
引用
收藏
页码:1590 / 1597
页数:8
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