15-Deoxy-Δ12,14-prostaglandin J2-induced apoptosis does not require PPARγ in breast cancer cells

Carl E. Clay, Arta M Monjazeb, Jacqueline Thorburn, Floyd H. Chilton, Kevin P. High

Research output: Contribution to journalArticle

99 Scopus citations

Abstract

Naturally occurring derivatives of arachidonic acid are potent agonists for the nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARγ) and block cancer cell proliferation through the induction of apoptosis. We have previously reported that induction of apoptosis using cyclopentenone prostaglandins of the J series, including 15deoxyΔ12,14PGJ2 (15dPGJ2), is associated with a high degree of PPAR-response element (PPRE) activity and requires early de novo gene expression in breast cancer cells. In the current study, we used pharmacologic and genetic approaches to test the hypothesis that PPARγ is required for 15dPGJ2-induced apoptosis. The PPARγ agonists 15dPGJ2, trogliltazone (TGZ), and GW7845, a synthetic and highly selective tyrosine-based PPARγ agonist, all increased transcriptional activity of PPARγ, and expression of CD36, a PPARγ-dependent gene. Transcriptional activity and CD36 expression was reduced by GW9662, a selective and irreversible PPARγ antagonist, but GW9662 did not block apoptosis induced by 15dPGJ2. Moreover, dominant negative expression of PPARγ blocked PPRE transcriptional activity, but did not block 15dPGJ2-induced apoptosis. These studies show that while 15dPGJ2 activates PPRE-mediated transcription, PPARγ is not required for 15dPGJ2-induced apoptosis in breast cancer cells. Other likely mechanisms through which cyclopentenone prostaglandins induce apoptosis of cancer cells are discussed.

Original languageEnglish (US)
Pages (from-to)1818-1828
Number of pages11
JournalJournal of Lipid Research
Volume43
Issue number11
DOIs
StatePublished - Nov 1 2002
Externally publishedYes

Keywords

  • Arachidonic acid metabolism
  • Cyclopentenone prostaglandins
  • Peroxisome proliferator-activated receptor γ

ASJC Scopus subject areas

  • Endocrinology

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