Antineoplastic effects of peroxisome proliferator-activated receptor γ agonists

Peroxisome proliferator-activated receptors (PPAR) are members of a superfamily of nuclear hormone receptors. Activation of PPAR isoforms elicits both antineoplastic and anti-inflammatory effects in several types of mammalian cells. PPARs are ligand-activated transcription factors and have a subfamily of three different isoforms: PPARalpha, PPARgamma, and PPARbeta/delta. All isoforms heterodimerise with the 9-cisretinoic acid receptor RXR, and play an important part in the regulation of several metabolic pathways, including lipid biosynthesis and glucose metabolism. Endogenous ligands of PPARgamma include long-chain polyunsaturated fatty acids, eicosanoid derivates, and oxidised lipids. Newly developed synthetic ligands include thiazolidinediones-a group of potent PPARgamma agonists and antidiabetic agents. Here, we review PPARgamma-induced antineoplastic signalling pathways, and summarise the antineoplastic effects of PPARgamma agonists in different cancer cell lines, animal models, and clinical trials.