Document Detail


15-deoxy-(Delta12,14)-prostaglandin J2 (15d-PGJ2) induces cell death through caspase-independent mechanism in A172 human glioma cells.
MedLine Citation:
PMID:  17006759     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
15-Deoxy-(Delta12,14)-prostaglandin J(2) (15d-PGJ(2)) is a naturally occurring cyclopentenone metabolite of prostaglandin D(2) (PGD(2)) and is known as a specific potent ligand for the peroxisome proliferators activator receptor-gamma (PPARgamma). 15d-PGJ(2) inhibits cell growth and induces apoptosis in a number of different cancer cells. However, the underlying mechanism by which 15d-PGJ(2) induces cell death remains to be defined. The present study was undertaken to determine the effect of 15d-PGJ(2) on cell death in A172 human glioma cells. 15d-PGJ(2) caused reactive oxygen species (ROS) generation. 15d-PGJ(2)-induced ROS production and cell death were prevented by the antioxidant N-acetylcysteine. Activation of mitogen-activated protein kinases (MAPK) was not observed in cells treated with 15d-PGJ(2 )and inhibitors of MAPK subfamilies also were not effective in preventing 15d-PGJ(2)-induced cell death. 15d-PGJ(2) treatment caused mitochondrial dysfunction, as evidenced by depolarization of mitochondrial membrane potential. 15d-PGJ(2) induced caspase activation at 24 h of treatment, but the 15d-PGJ(2)-induced cell death was not prevented by caspase inhibitors. The antiapoptotic protein XIAP levels and release of apoptosis inducing factor (AIF) into the cytosol were not altered by 15d-PGJ(2) treatment. Taken together, these findings indicate that 15d-PGJ(2) triggers cell death through a caspase-independent mechanism and ROS production and disruption of mitochondrial membrane potential play an important role in the 15d-PGJ(2)-induced cell death in A172 human glioma cells.
Authors:
W H Cho; C H Choi; J Y Park; S K Kang; Y K Kim
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neurochemical research     Volume:  31     ISSN:  0364-3190     ISO Abbreviation:  Neurochem. Res.     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-11-03     Completed Date:  2007-01-24     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7613461     Medline TA:  Neurochem Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1247-54     Citation Subset:  IM    
Affiliation:
Department of Neurosurgery, College of Medicine, Pusan National University, Pusan, 602-739, Korea.
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MeSH Terms
Descriptor/Qualifier:
Brain Neoplasms / enzymology,  metabolism,  pathology*
Caspases / metabolism
Cell Death / drug effects*
Cell Line, Tumor
Glioma / enzymology,  metabolism,  pathology*
Humans
Mitogen-Activated Protein Kinases / antagonists & inhibitors,  metabolism
Prostaglandin D2 / analogs & derivatives*,  pharmacology
Reactive Oxygen Species / metabolism
Chemical
Reg. No./Substance:
0/15-deoxyprostaglandin J2; 0/Reactive Oxygen Species; 41598-07-6/Prostaglandin D2; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 3.4.22.-/Caspases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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