title: Antineoplastic effects of peroxisome proliferator-activated receptor gamma agonists.
abstract: 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: PPAR alpha, PPAR gamma, and PPAR beta/delta. All isoforms heterodimerise with the 9-cis-retinoic acid receptor RXR, and play an important part in the regulation of several metabolic pathways, including lipid biosynthesis and glucose metabolism. Endogenous ligands of PPAR gamma include long-chain polyunsaturated fatty acids, eicosanoid derivates, and oxidised lipids. Newly developed synthetic ligands include thiazolidinediones-a group of potent PPAR gamma agonists and antidiabetic agents. Here, we review PPAR gamma-induced antineoplastic signalling pathways, and summarise the antineoplastic effects of PPAR gamma agonists in different cancer cell lines, animal models, and clinical trials.
authors.affiliation: Department of Neurosciences, Alzheimer Research Laboratory, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Grommes
authors.forename: Gary E
authors.initials: GE
authors.lastname: Landreth
authors.forename: Michael T
authors.initials: MT
authors.lastname: Heneka
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002986:Clinical Trials as Topic; D006801:Humans; D023421:Models, Animal; D009369:Neoplasms / Q000188:drug therapy*; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000627:therapeutic use; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000819:agonists / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors