title: Non-steroidal anti-inflammatory drugs induce apoptosis in gastric cancer cells through up-regulation of bax and bak.
abstract: Aspirin- and non-steroidal anti-inflammatory drug (NSAID)-induced apoptosis is one of the important mechanisms for their anti-tumour effect in gastric cancer. We aimed at determining the role of bcl-2 family proteins and caspases in the apoptotic process. Gastric cancer cell lines AGS (wild-type p53) and MKN-28 (mutant p53) were used. Cell proliferation was measured by MTT assay. Apoptosis was determined by acridine orange staining. Protein expressions were determined by western blotting. Aspirin and indomethacin inhibited cell proliferation and induced apoptosis in both cells. AGS cells were more sensitive compared with MKN-28 cells. The pro-apoptotic proteins bax and bak were overexpressed after treatment, while the protein level of bcl-2 remained unchanged. Apoptosis was accompanied by an increase in caspase-3 activity and cleavage of caspase-3 and poly(ADP-ribose) polymerase. Inhibition of caspase-3 rescued aspirin-induced apoptosis. Our results suggest that one of the major pathways which mediates the anti-tumour response of aspirin and indomethacin in gastric cancer cells is through up-regulation of bax and bak and activation of caspase-3. Bax and bak are important in the chemoprevention of gastric cancer.
authors.affiliation: Department of Medicine and Institute of Molecular Biology, University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: X M
authors.initials: XM
authors.lastname: Zhou
authors.forename: B C
authors.initials: BC
authors.lastname: Wong
authors.forename: X M
authors.initials: XM
authors.lastname: Fan
authors.forename: H B
authors.initials: HB
authors.lastname: Zhang
authors.forename: M C
authors.initials: MC
authors.lastname: Lin
authors.forename: H F
authors.initials: HF
authors.lastname: Kung
authors.forename: D M
authors.initials: DM
authors.lastname: Fan
authors.forename: S K
authors.initials: SK
authors.lastname: Lam
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001241:Aspirin / Q000494:pharmacology*; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000096:biosynthesis / Q000235:genetics; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C494772:BAK1 protein, human; C494826:BAX protein, human; C494811:BCL2L1 protein, human; D061945:Caspase Inhibitors; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D001241:Aspirin; D007213:Indomethacin