Changes of NF-kB, p53, Bcl-2 and Caspase in Apoptosis Induced by JTE-522 in Human Gastric Adenocarcinoma Cell Line AGS Cells: Role of Reactive Oxygen Species

World J Gastroenterol. 2002 Jun;8(3):431-5. doi: 10.3748/wjg.v8.i3.431.


Aim: To identify whether JTE-522 can induce apoptosis in AGS cells and ROS also involved in the process, and to investigate the changes in NF-kB, p53, bcl-2 and caspase in the apoptosis process.

Methods: Cell culture, MTT, Electromicroscopy, agarose gel electrophoresis, lucigenin, Western blot and electrophoretic mobility shift assay (EMSA) analysis were employed to investigate the effect of JTE-522 on cell proliferation and apoptosis in AGS cells and related molecular mechanisms.

Results: JTE-522 inhibited the growth of AGS cells and induced the apoptosis. Lucigenin assay showed the generation of ROS in cells under incubation with JTE-522. The increased ROS generation might contribute to the induction of AGS cells to apoptosis. EMSA and Western blot revealed that NF-kB activity was almost completely inhibited by preventing the degradation of IkBalpha. Additionally, by using Western blot we confirmed that the level of bcl-2 was decreased, whereas p53 showed a great increase following JTE-522 treatment. Their changes were in a dose-dependent manner.

Conclusion: These findings suggest that reactive oxygen species, NF-kB, p53, bcl-2 and caspase-3 may play an important role in the induction of apoptosis in AGS cells after treatment with JTE-522.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Apoptosis / drug effects
  • Benzenesulfonates / pharmacology
  • Caspases / metabolism
  • Cell Division / drug effects
  • DNA-Binding Proteins / metabolism
  • Humans
  • I-kappa B Proteins*
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / metabolism
  • Oxazoles / pharmacology
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reactive Oxygen Species / metabolism
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / metabolism


  • 4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide
  • Benzenesulfonates
  • DNA-Binding Proteins
  • I-kappa B Proteins
  • NF-kappa B
  • NFKBIA protein, human
  • Oxazoles
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • Tumor Suppressor Protein p53
  • NF-KappaB Inhibitor alpha
  • Caspases