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: Qing Gu, Ji De Wang, Harry H X Xia, Marie C M Lin, Hua He, Bing Zou, Shui Ping Tu, Yi Yang, Xin Guang Liu, Shiu Kum Lam, Wai Man Wong, Annie O O Chan, Man Fung Yuen, Hsiang Fu Kung, Benjamin Chun-Yu Wong
• Journal: Carcinogenesis (Carcinogenesis) Vol. 26 Issue 3 Pg. 541-6 (Mar 2005) ISSN: 0143-3334 [Print] England
• PMID: 15579484 (Publication Type: Journal Article)

Chemical References

• BAX protein, human
• BH3 Interacting Domain Death Agonist Protein
• BID protein, human
• Carrier Proteins
• Caspase Inhibitors
• Cysteine Proteinase Inhibitors
• Proto-Oncogene Proteins c-bcl-2
• bcl-2-Associated X Protein
• Cytochromes c
• Poly(ADP-ribose) Polymerases
• CASP3 protein, human
• CASP8 protein, human
• Caspase 3
• Caspase 8
• Caspases
• Aspirin

Topics

• Apoptosis (drug effects)
• Aspirin (pharmacology)
• BH3 Interacting Domain Death Agonist Protein
• Carrier Proteins (metabolism)
• Caspase 3
• Caspase 8
• Caspase Inhibitors
• Caspases (metabolism)
• Cell Line, Tumor
• Cysteine Proteinase Inhibitors (pharmacology)
• Cytochromes c (metabolism)
• Enzyme Activation
• Humans
• Poly(ADP-ribose) Polymerases (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Stomach Neoplasms (enzymology, metabolism, pathology)
• bcl-2-Associated X Protein