The influence of peroxisome proliferator-activated receptor γ (PPARγ) ligands on cancer cell tumorigenicity

Peroxisome proliferator-activated receptor gamma (PPAR gamma) belongs to the nuclear receptor superfamily of PPARs (PPAR alpha, PPAR beta/delta, PPAR gamma). Numerous studies have concentrated on the key role of PPARs in inflammation and a variety of cancers which include prostate, breast, glioblastoma, neuroblastoma, pancreatic, hepatic, leukemia, and bladder and thyroid tumors. This review, specifically deals with anti-tumor and tumorigenicity effects of PPAR gamma and its natural and synthetic agonists including Troglitazone, Cladosporol A, B, 15-Deoxi-Delta(12-14)-Prostaglondin J2 (15-d-PGJ2), Ciglitazon, docosahexaenoic acid, eicosapentaenoic acid Alpha-eleostreac acid, Amorfrutin C, Sphingosine 1-phosphate, Evodiamine, Excavatolide B vs respected antagonists as GW9662, bisphenol-A-diglycidyl-ether. Considering the contradictory role of PPAR gamma on tumorigenicity, a number of studies demonstrate mechanisms involved in tumorigenicity effects of PPAR gamma agonists while several studies suggest key roles of PPAR gamma agonists in anti-proliferation, metastasis, angiogenesis, apoptosis and immunomodulatory through activation of signaling pathways in different cancer cells as well as in cancer stem cells. The aim of this review is summarizing of tumorigenicity and anti-tumorigenicity activities of PPAR gamma agonists and antagonists as well as therapeutic activities of these reagents as a coadjutant drug in the treatment of different cancers.