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Involvement of c‐jun N‐terminal kinase activation in 15‐deoxy‐δ 12,14 ‐prostaglandin J 2 –and prostaglandin A 1 –induced apoptosis in AGS gastric epithelial cells
Author(s) -
Liu JeanDean,
Lin ShyrYi,
Ho YuanSoon,
Pan Shiann,
Hung LingFang,
Tsai ShuHuei,
Lin JenKun,
Liang YuChih
Publication year - 2003
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.10119
Subject(s) - apoptosis , biology , kinase , transfection , prostaglandin , prostaglandin d2 , dna fragmentation , microbiology and biotechnology , c jun , programmed cell death , endocrinology , biochemistry , transcription factor , gene
Cyclopentenone prostaglandins (CyPGs), derivatives of arachidonic acid, have been suggested to exert growth‐inhibitory activity through peroxisome proliferator‐activated receptor (PPAR)‐dependent and ‐independent mechanisms. Here we examined various eicosanoids for growth inhibition and found that the terminal derivative of prostaglandin (PG) J 2 metabolism, 15‐deoxy‐Δ 12,14 ‐PGJ 2 (15d‐PGJ 2 ), and PGA 1 markedly inhibited the growth and induced apoptosis in AGS gastric carcinoma cells. There were no significant increases in cell death and DNA‐fragmentation in the cells with overexpression of PPARα or PPARγ, indicating the possibility that 15d‐PGJ 2 and PGA 1 induced apoptosis through PPAR‐independent pathway. Moreover, 15d‐PGJ 2 and PGA 1 activated the c‐jun N‐terminal kinase (JNK) and caspase‐3 activity in dose‐ and time‐dependent manners. To examine further the role of JNK signaling cascades in apoptosis induced by 15d‐PGJ 2 and PGA 1 , we transfected dominant‐negative (DN) mutants of JNK plasmid into the cells to analyze the apoptotic characteristics of cells overexpressing DN‐JNK following exposure to 15d‐PGJ 2 and PGA 1 . Overexpression of DN‐JNK significantly repressed both endogenous JNK and caspase‐3 activity, and subsequently decreased apoptosis induced by 15d‐PGJ 2 and PGA 1 . These results suggested that CyPGs, such as 15d‐PGJ 2 and PGA 1 , activated JNK signaling pathway, and that JNK activation may be involved in 15d‐PGJ 2 ‐ and PGA 1 ‐induced apoptosis. © 2003 Wiley‐Liss, Inc.