Document Detail


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.
MedLine Citation:
PMID:  12046064     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Hong-Liang Li; Dan-Dan Chen; Xiao-Hong Li; Hai-Wei Zhang; Yan-Qing Lu; Chun-Ling Ye; Xian-Da Ren
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  World journal of gastroenterology : WJG     Volume:  8     ISSN:  1007-9327     ISO Abbreviation:  World J. Gastroenterol.     Publication Date:  2002 Jun 
Date Detail:
Created Date:  2002-06-04     Completed Date:  2002-08-06     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  100883448     Medline TA:  World J Gastroenterol     Country:  China    
Other Details:
Languages:  eng     Pagination:  431-5     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Jinan University Pharmacy College, Guangzhou 510632, Guangdong, China.
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / metabolism*,  pathology
Apoptosis / drug effects
Benzenesulfonates / pharmacology
Caspases / metabolism
Cell Division / drug effects
DNA-Binding Proteins / metabolism
Humans
I-kappa B Proteins*
NF-kappa B / metabolism
Oxazoles / pharmacology
Proto-Oncogene Proteins c-bcl-2 / metabolism
Reactive Oxygen Species / metabolism
Stomach Neoplasms / metabolism*,  pathology
Tumor Cells, Cultured
Tumor Suppressor Protein p53 / metabolism
Chemical
Reg. No./Substance:
0/4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide; 0/Benzenesulfonates; 0/DNA-Binding Proteins; 0/I-kappa B Proteins; 0/NF-kappa B; 0/Oxazoles; 0/Proto-Oncogene Proteins c-bcl-2; 0/Reactive Oxygen Species; 0/Tumor Suppressor Protein p53; 139874-52-5/NF-kappaB inhibitor alpha; EC 3.4.22.-/Caspases

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