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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.

ARTICLE

Activation of the caspase-8/Bid and Bax pathways in aspirin-induced apoptosis in gastric cancer

Qing Gu1,2, Ji De Wang2, Harry H.X. Xia2, Marie C.M. Lin3, Hua He2, Bing Zou2, Shui Ping Tu2, Yi Yang2, Xin Guang Liu1, Shiu Kum Lam2, Wai Man Wong2, Annie O.O. Chan2, Man Fung Yuen2, Hsiang Fu Kung3 and Benjamin Chun-Yu Wong2,4

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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