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

0340714 - BTÚ 2010 RIV IE eng J - Journal Article
Zhao, Y. - Li, R. - Xia, W. - Neužil, Jiří - Lu, Y. - Zhang, H. - Zhao, X. - Zhang, X. - Sun, C. - Wu, K.
Bid integrates intrinsic and extrinsic signaling in apoptosis induced by alpha-tocopheryl succinate in human gastric carcinoma cells.
Cancer letters. Roč. 288, č. 1 (2010), s. 42-49. ISSN 0304-3835. E-ISSN 1872-7980
R&D Projects: GA ČR(CZ) GA204/08/0811
Institutional research plan: CEZ:AV0Z50520701
Keywords : Alpha-tocopheryl succinate * signaling * apoptosis
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 4.864, year: 2010

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. 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.
Permanent Link: http://hdl.handle.net/11104/0183901