15-deoxy-(Delta12,14)-prostaglandin J2 (15d-PGJ2) induces cell death through caspase-independent mechanism in A172 human glioma cells.
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.
Cho
W H
WH
Department of Neurosurgery, College of Medicine, Pusan National University, Pusan, 602-739, Korea.
Choi
C H
CH
Park
J Y
JY
Kang
S K
SK
Kim
Y K
YK
D001932:Brain Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D005910:Glioma / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism
C477819:15-deoxyprostaglandin J2; D017382:Reactive Oxygen Species; D020928:Mitogen-Activated Protein Kinases; D020169:Caspases; D015230:Prostaglandin D2