Neurochemical Research

, Volume 31, Issue 10, pp 1247–1254 | Cite as

15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) Induces Cell Death Through Caspase-independent Mechanism in A172 Human Glioma Cells

  • W. H. Cho
  • C. H. Choi
  • J. Y. Park
  • S. K. Kang
  • Y. K. Kim
Original Paper


15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is a naturally occurring cyclopentenone metabolite of prostaglandin D2 (PGD2) and is known as a specific potent ligand for the peroxisome proliferators activator receptor-γ (PPARγ). 15d-PGJ2 inhibits cell growth and induces apoptosis in a number of different cancer cells. However, the underlying mechanism by which 15d-PGJ2 induces cell death remains to be defined. The present study was undertaken to determine the effect of 15d-PGJ2 on cell death in A172 human glioma cells. 15d-PGJ2 caused reactive oxygen species (ROS) generation. 15d-PGJ2-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-PGJ2 and inhibitors of MAPK subfamilies also were not effective in preventing 15d-PGJ2-induced cell death. 15d-PGJ2 treatment caused mitochondrial dysfunction, as evidenced by depolarization of mitochondrial membrane potential. 15d-PGJ2 induced caspase activation at 24 h of treatment, but the 15d-PGJ2-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-PGJ2 treatment. Taken together, these findings indicate that 15d-PGJ2 triggers cell death through a caspase-independent mechanism and ROS production and disruption of mitochondrial membrane potential play an important role in the 15d-PGJ2-induced cell death in A172 human glioma cells.


15d-PGJ2 Caspase-independent apoptosis Mitochondrial depolarization Reactive oxygen species Human A172 glioma cells 



This work was partly supported by the program of MOST/KOSEF (R13–2005–009).


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Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  • W. H. Cho
    • 1
  • C. H. Choi
    • 1
  • J. Y. Park
    • 2
  • S. K. Kang
    • 2
  • Y. K. Kim
    • 2
    • 3
  1. 1.Department of Neurosurgery, College of MedicinePusan National UniversityPusanKorea
  2. 2.Department of Physiology, College of MedicinePusan National UniversityPusanKorea
  3. 3.Department of MRC for ischemic tissue regeneration, College of MedicinePusan National UniversityPusanKorea

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