Bid integrates intrinsic and extrinsic signaling in apoptosis induced by α-tocopheryl succinate in human gastric carcinoma cells

被引:37
作者
Zhao, Yan [1 ]
Li, Ruisong [1 ]
Xia, Wei [1 ]
Neuzil, Jiri [2 ,3 ]
Lu, Yuxia [1 ]
Zhang, Haijin [1 ]
Zhao, Xiujuan [1 ]
Zhang, Xiaohua [1 ]
Sun, Changhao [1 ]
Wu, Kun [1 ]
机构
[1] Harbin Med Univ, Dept Nutr & Food, Harbin, Peoples R China
[2] Griffith Univ, Apoptosis Res Grp, Sch Med Sci, Southport, Qld 4215, Australia
[3] Acad Sci Czech Republ, Inst Mol Genet, Mol Therapy Grp, Prague, Czech Republic
基金
中国国家自然科学基金; 澳大利亚研究理事会;
关键词
Apoptosis; Bid; Gastric carcinoma; alpha-tocopheryl succinate; PERMEABILITY TRANSITION PORE; VITAMIN-E ANALOGS; PROSTATE-CANCER CELLS; BREAST-CANCER; CYTOCHROME-C; ANTICANCER AGENTS; BAX TRANSLOCATION; MITOCHONDRIA; DEATH; RELEASE;
D O I
10.1016/j.canlet.2009.06.021
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The underlying mechanisms of alpha-tocopheryl succinate (alpha-TOS)-mediated apoptosis are not understood in detail, although the redox-silent vitamin E analog is a potent apoptogen and anti-cancer agent. Our previous studies showed the important role of Fas signaling in apoptosis induced by the mitocan. The objective of the present study was to investigate whether apoptosis triggered by alpha-TOS in gastric carcinomas cells involves both mitochondria- and death receptor-dependent pathways. alpha-TOS induced apoptosis and mitochondrial permeability transition in a concentration- and time-dependent manner. As a consequence, cytochrome c and the apoptosis-inducing factor were released and caspases were activated. Bax was translocated from the cytosol to mitochondria. and Bid was cleaved into its truncated form, tBid. Knocking down Bid by RNAi and Fas antisense oligodeoxynucleotides resulted in a decreased release and cleavage. The results imply that Bid may serve as a critical integrating factor of the death receptor and mitochondrial pathway in alpha-TOS-mediated apoptosis. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:42 / 49
页数:8
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