The role of 15-deoxy-Δ12,14-prostaglandin J2, an endogenous ligand of peroxisome proliferator-activated receptor γ, in tumor angiogenesis

Abstract

Peroxisome proliferator-activated receptor gamma (PPAR gamma), a nuclear hormone receptor, is a ligand-activated transcription factor involved in adipogenesis, glucose homeostasis and lipid metabolism. 15-Deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), an endogenous ligand of PPAR gamma, has multifaceted cellular functions. Angiogenesis plays an important role in the pathophysiology of ischemic and neoplastic disorders, especially cancer. 15d-PGJ2 is involved in regulation of angiogenic mediators including vascular endothelial growth factor and hence participates in the blood vessel formation by means of angiogenesis. However, depending on the experimental conditions, this cyclopentenone prostaglandin can exert opposite effects on angiogenesis. 15d-PGJ(2) inhibits angiogenesis via suppression of pro-inflammatory enzymes and cytokines, while it also stimulates angiogenesis via induction of heme oxygenase-1, endothelial nitric-oxide synthase, and hypoxia inducible factor-la. The aim of this review is to highlight such dual effects of 15d-PGJ2 on angiogenesis and underlying molecular mechanisms. (C) 2008 Elsevier Inc. All rights reserved.