The role of 15-deoxy-delta(12,14)-prostaglandin J(2), an endogenous ligand of peroxisome proliferator-activated receptor gamma, in tumor angiogenesis.
Peroxisome proliferator-activated receptor gamma (PPARgamma), 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 PPARgamma, has multifaceted cellular functions. Angiogenesis plays an important role in the pathophysiology of ischemic and neoplastic disorders, especially cancer. 15d-PGJ(2) 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-1alpha. The aim of this review is to highlight such dual effects of 15d-PGJ(2) on angiogenesis and underlying molecular mechanisms.
Kim
Eun-Hee
EH
National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
Surh
Young-Joon
YJ
D006801:Humans; D008024:Ligands; D009369:Neoplasms / Q000098:blood supply*; D009389:Neovascularization, Pathologic; D047495:PPAR gamma / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000378:metabolism / Q000502:physiology
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D008024:Ligands; D047495:PPAR gamma; D015230:Prostaglandin D2