JTE-522-induced apoptosis in human gastric adenocarcinoma [correction of adenocarcinoma] cell line AGS cells by caspase activation accompanying cytochrome C release, membrane translocation of Bax and loss of mitochondrial membrane potential.

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  • Author(s): Li HL;Li HL; Chen DD; Li XH; Zhang HW; Lü JH; Ren XD; Wang CC
  • Source:
    World journal of gastroenterology [World J Gastroenterol] 2002 Apr; Vol. 8 (2), pp. 217-23.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Baishideng Publishing Group Country of Publication: United States NLM ID: 100883448 Publication Model: Print Cited Medium: Print ISSN: 1007-9327 (Print) Linking ISSN: 10079327 NLM ISO Abbreviation: World J Gastroenterol Subsets: MEDLINE
    • Publication Information:
      Publication: 2014- : Pleasanton, CA : Baishideng Publishing Group
      Original Publication: Beijing : WJG Press, c1998-
    • Subject Terms:
      Adenocarcinoma* ; Stomach Neoplasms*; Apoptosis/*drug effects ; Benzenesulfonates/*pharmacology ; Caspases/*metabolism ; Cytochrome c Group/*metabolism ; Mitochondria/*drug effects ; Oxazoles/*pharmacology ; Proto-Oncogene Proteins/*metabolism; Amino Acid Chloromethyl Ketones/pharmacology ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology ; Apoptosis/physiology ; Caspase Inhibitors ; Cyclooxygenase Inhibitors/pharmacology ; Cysteine Proteinase Inhibitors/pharmacology ; Enzyme Activation ; Humans ; In Situ Nick-End Labeling ; Membrane Potentials/physiology ; Mitochondria/metabolism ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Tumor Cells, Cultured ; bcl-2-Associated X Protein
    • Abstract:
      Aim: To investigate the role of the mitochondrial pathway in JTE-522-induced apoptosis and to investigate the relationship between cytochrome C release, caspase activity and loss of mitochondrial membrane potential (Deltapsim).
      Methods: Cell culture, cell counting, ELISA assay, TUNEL, flow cytometry, Western blot and fluorometric assay were employed to investigate the effect of JTE-522 on cell proliferation and apoptosis in AGS cells and related molecular mechanism.
      Results: JTE-522 inhibited the growth of AGS cells and induced the apoptosis. Caspases 8 and 9 were activated during apoptosis as judged by the appearance of cleavage products from procaspase and the caspase activities to cleave specific fluorogenic substrates. To elucidate whether the activation of caspases 8 and 9 was required for the apoptosis induction, we examined the effect of caspase-specific inhibitors on apoptosis. The results showed that caspase inhibitors significantly inhibited the apoptosis induced by JTE-522. In addition, the membrane translocation of Bax and cytosolic release of cytochrome C accompanying with the decrease of the uptake of Rhodamin 123, were detected at an early stage of apoptosis. Furthermore, Bax translocation, cytochrome C release, and caspase 9 activation were blocked by Z-VAD.fmk and Z-IETD-CHO.
      Conclusion: The present data indicate a crucial association between activation of caspases 8, 9, cytochrome C release, membrane translocation of Bax, loss of Deltapsim and JTE-522-induced apoptosis in AGS cells.
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    • Accession Number:
      0 (4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide)
      0 (Amino Acid Chloromethyl Ketones)
      0 (Anti-Inflammatory Agents, Non-Steroidal)
      0 (BAX protein, human)
      0 (Benzenesulfonates)
      0 (Caspase Inhibitors)
      0 (Cyclooxygenase Inhibitors)
      0 (Cysteine Proteinase Inhibitors)
      0 (Cytochrome c Group)
      0 (Oxazoles)
      0 (Proto-Oncogene Proteins)
      0 (Proto-Oncogene Proteins c-bcl-2)
      0 (bcl-2-Associated X Protein)
      0 (benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone)
      EC 3.4.22.- (Caspases)
    • Publication Date:
      Date Created: 20020402 Date Completed: 20021203 Latest Revision: 20190430
    • Publication Date:
      20240829
    • Accession Number:
      PMC4658354
    • Accession Number:
      10.3748/wjg.v8.i2.217
    • Accession Number:
      11925595