title: Activation of the caspase-8/Bid and Bax pathways in aspirin-induced apoptosis in gastric cancer.
abstract: 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.
authors.affiliation: Department of Gastroenterology, First Hospital, Peking University, Beijing, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Gu
authors.forename: Ji De
authors.initials: JD
authors.lastname: Wang
authors.forename: Harry H X
authors.initials: HH
authors.lastname: Xia
authors.forename: Marie C M
authors.initials: MC
authors.lastname: Lin
authors.forename: Hua
authors.initials: H
authors.lastname: He
authors.forename: Bing
authors.initials: B
authors.lastname: Zou
authors.forename: Shui Ping
authors.initials: SP
authors.lastname: Tu
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Xin Guang
authors.initials: XG
authors.lastname: Liu
authors.forename: Shiu Kum
authors.initials: SK
authors.lastname: Lam
authors.forename: Wai Man
authors.initials: WM
authors.lastname: Wong
authors.forename: Annie O O
authors.initials: AO
authors.lastname: Chan
authors.forename: Man Fung
authors.initials: MF
authors.lastname: Yuen
authors.forename: Hsiang Fu
authors.initials: HF
authors.lastname: Kung
authors.forename: Benjamin Chun-Yu
authors.initials: BC
authors.lastname: Wong
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001241:Aspirin / Q000494:pharmacology*; D051023:BH3 Interacting Domain Death Agonist Protein; D002352:Carrier Proteins / Q000378:metabolism*; D053148:Caspase 3; D053181:Caspase 8; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D002352:Carrier Proteins; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; C505530:CASP8 protein, human; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases; D001241:Aspirin