Involvement of c-jun N-terminal kinase activation in 15-deoxy-delta12,14-prostaglandin J2-and prostaglandin A1-induced apoptosis in AGS gastric epithelial cells

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 t...

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Bibliographic Details
Published in:Molecular carcinogenesis 2003-05, Vol.37 (1), p.16-24
Main Authors: Liu, Jean-Dean, Lin, Shyr-Yi, Ho, Yuan-Soon, Pan, Shiann, Hung, Ling-Fang, Tsai, Shu-Huei, Lin, Jen-Kun, Liang, Yu-Chih
Format: Article
Language:English
Subjects:
Apoptosis - drug effects
Caspase 3
Caspases - metabolism
Cell Division - drug effects
Enzyme Activation - drug effects
Humans
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinases - genetics
Mitogen-Activated Protein Kinases - metabolism
Mutation
Prostaglandin D2 - analogs & derivatives
Prostaglandin D2 - pharmacology
Prostaglandins A - pharmacology
Receptors, Cytoplasmic and Nuclear - metabolism
Signal Transduction
Stomach Neoplasms - pathology
Transcription Factors - metabolism
Transfection
Tumor Cells, Cultured
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Summary: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-Delta(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 PPARalpha or PPARgamma, 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.
ISSN:0899-1987