title: Overexpression of protein kinase C-beta1 isoenzyme suppresses indomethacin-induced apoptosis in gastric epithelial cells.
abstract: OBJECTIVE
  We have previously reported that nonsteroidal anti-inflammatory drugs (NSAIDs) could induce apoptosis of gastric epithelial cells both in vivo and in vitro. This study investigated the role of protein kinase C (PKC) isoforms in the regulation of NSAID-induced apoptosis.
  
  
  METHODS
  Protein levels of 12 PKC isoforms in AGS cells, in the presence or absence of indomethacin, were determined by Western blot. The effect of PKC-beta1 overexpression by transfection with its complementary DNA (cDNA) on indomethacin-induced apoptosis and apoptosis-related genes, including p53, p21(waf1/cip1), and c-myc, was further investigated.
  
  
  RESULTS
  Treatment with indomethacin decreased the abundance of PKC-beta1 and increased that of PKC-beta2, eta, and epsilon, but did not alter the expression of PKC alpha, gamma, zeta, delta, iota, and micro. Overexpression of PKC-beta1 attenuated the apoptotic response of AGS cells to indomethacin, associated with overexpression of p21(waf1/cip1) in both messenger RNA and protein levels. Inhibition of PKC-beta1-mediated overexpression of p21(waf1/cip1) by its antisense cDNA partially reduced the antiapoptotic effect of PKC-beta1.
  
  
  CONCLUSIONS
  Indomethacin-induced apoptosis in gastric cancer cells is partly mediated by differential regulation of PKC isoform expression. Enhanced expression of exogenous PKC-beta1 protects against indomethacin-induced apoptosis through up-regulation of p21(waf1/cip1).
authors.affiliation: Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, P.R. China.
authors.forename: G H
authors.initials: GH
authors.lastname: Zhu
authors.forename: B C
authors.initials: BC
authors.lastname: Wong
authors.forename: E D
authors.initials: ED
authors.lastname: Slosberg
authors.forename: M C
authors.initials: MC
authors.lastname: Eggo
authors.forename: C K
authors.initials: CK
authors.lastname: Ching
authors.forename: S T
authors.initials: ST
authors.lastname: Yuen
authors.forename: K C
authors.initials: KC
authors.lastname: Lai
authors.forename: J W
authors.initials: JW
authors.lastname: Soh
authors.forename: I B
authors.initials: IB
authors.lastname: Weinstein
authors.forename: S K
authors.initials: SK
authors.lastname: Lam
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016375:Antisense Elements (Genetics) / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D018076:DNA, Complementary / Q000494:pharmacology; D005753:Gastric Mucosa / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D064546:Protein Kinase C beta; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016375:Antisense Elements (Genetics); D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D018076:DNA, Complementary; D007527:Isoenzymes; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D007213:Indomethacin