Carcinogenesis Advance Access originally published online on December 3, 2004
Carcinogenesis 2005 26(3):541-546; doi:10.1093/carcin/bgh345
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Carcinogenesis vol.26 no.3 © Oxford University Press 2004; all rights reserved.
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Activation of the caspase-8/Bid and Bax pathways in aspirin-induced apoptosis in gastric cancer
1 Department of Gastroenterology, First Hospital, Peking University, Beijing, People's Republic of China, 2 Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong and 3 Institute of Molecular Biology, University of Hong Kong, Hong Kong
4 To whom correspondence should be addressed. Tel: +86 852 2855 4541; Fax: +86 852 2872 5828; Email: bcywong{at}hku.hk
Aspirin-induced apoptosis is one of the important mechanisms for its antitumour effect against gastric cancer. We aimed at investigating the involvement of bcl-2 family members in the apoptotic pathway in gastric cancer. Gastric cancer cell line AGS and MKN-45 were observed as to cell growth inhibition and induction of apoptosis in response to treatment with aspirin. Cell proliferation was measured by MTT assay. Apoptosis was determined by 4'-6-diamidino-2-phenylindole staining. Protein expression was determined by western blotting. We showed that aspirin activated caspase-8, caspase-9 and capase-3, cleaved and translocated Bid, induced a conformational change in and translocation of Bax and cytochrome c release. In addition, suppression of caspase-8 with the specific inhibitor z-IETD-fmk, as well as the pan-caspase inhibitor z-VAD-fmk, prevented Bid cleavage and subsequent apoptosis. The caspase inhibitors failed to abolish the effects on Bax activation. In conclusion, our results identify a role of caspase-8/Bid and activation of Bax as a novel mechanism for aspirin-induced apoptosis in gastric cancer.
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