The potential of antidiabetic thiazolidinediones for anticancer therapy.
The thiazolidinediones (TZDs) are a class of synthetic compounds for treatment of insulin-resistant Type 2 diabetes mellitus. TZDs are known activators of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma), and exert their antidiabetic action largely through this nuclear receptor family. Moreover, increasing experimental evidences of PPAR-gamma-independent effects are accumulating. Apart from the established metabolic actions, TZD treatment exerts additional biological effect such as control of cell growth, differentiation, motility and programmed cell death. In this context, considerable interest has focused on TZDs as potential chemopreventive agents in oncology; however, despite encouraging observation on the potential anticancer effect of these drugs in several in vitro experimental models, controversial results have been obtained with animal models and in pilot clinical trials. This review summarises the molecular mechanisms of the antineoplastic actions of TZDs and the relevance of these findings in human pathology and therapy.
Galli
Andrea
A
University of Florence, Gastroenterology Unit, Department of Clinical Pathophysiology, Viale Morgani 85,50134 - Firenze, Florence, Italy. a.galli@dfc.unifi.it
Mello
Tommaso
T
Ceni
Elisabetta
E
Surrenti
Elisabetta
E
Surrenti
Calogero
C
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002471:Cell Transformation, Neoplastic; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045162:Thiazolidinediones / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones