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15-Deoxy-delta12,14-prostaglandin J2-induced apoptosis does not require PPARgamma in breast cancer cells

Carl E Clay1, Arta Monjazeb, Jacqueline Thorburn

  • 1Department of Cancer Biology, Wake Forest University Baptist Medical Center, Medical Center Boulevard, Winston Salem, NC 27157, USA.

Journal of Lipid Research
|October 29, 2002
PubMed

Insights

Cyclopentenone prostaglandins like 15dPGJ(2) induce apoptosis in breast cancer cells. However, this study found that peroxisome proliferator-activated receptor gamma (PPARgamma) is not required for this cancer cell death.

Area of Science:

  • Molecular biology
  • Cancer research
  • Endocrinology

Background:

  • Arachidonic acid derivatives, such as cyclopentenone prostaglandins (e.g., 15dPGJ(2)), are known to activate peroxisome proliferator-activated receptor gamma (PPARgamma).
  • PPARgamma activation can lead to apoptosis and inhibit cancer cell proliferation.
  • Previous research indicated that 15dPGJ(2)-induced apoptosis in breast cancer cells involves PPAR-response element (PPRE) activity and gene expression.

Purpose of the Study:

  • To investigate the role of PPARgamma in 15dPGJ(2)-induced apoptosis in breast cancer cells.
  • To determine if PPARgamma is a necessary mediator for the anti-cancer effects of 15dPGJ(2).

Main Methods:

  • Utilized pharmacologic agents, including PPARgamma agonists (15dPGJ(2), trogliltazone, GW7845) and an antagonist (GW9662).
  • Employed genetic approaches, specifically dominant-negative expression of PPARgamma.
  • Assessed PPARgamma transcriptional activity, PPRE activity, CD36 gene expression, and apoptosis induction.

Main Results:

  • PPARgamma agonists increased PPARgamma transcriptional activity and CD36 expression, which was inhibited by the PPARgamma antagonist GW9662.
  • However, the PPARgamma antagonist GW9662 did not prevent 15dPGJ(2)-induced apoptosis.
  • Dominant-negative PPARgamma expression blocked PPRE activity but did not inhibit 15dPGJ(2)-induced apoptosis, indicating PPARgamma is not essential for this process.

Conclusions:

  • While 15dPGJ(2) activates PPARgamma-mediated transcription, PPARgamma is not required for 15dPGJ(2)-induced apoptosis in breast cancer cells.
  • Suggests alternative molecular mechanisms are responsible for the apoptotic effects of cyclopentenone prostaglandins on cancer cells.
  • Highlights the complexity of signaling pathways involved in cancer cell death induced by natural compounds.

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