title: Deciphering the Roles of Thiazolidinediones and PPARγin Bladder Cancer.
abstract: The use of thiazolidinedione (TZD) therapy in type II diabetic patients has proven useful in the lowering of blood glucose levels. However, recent investigations have shown that there may be potential health concerns associated, including the risk of developing bladder cancer as well as complications in the cardiovasculature. TZDs are ligands for the nuclear receptor PPARγ, and activation causes lipid uptake and insulin sensitization, both of which are critical processes for diabetic patients whose bodies are unable to utilize insulin effectively. Several studies have shown that PPARγ/TZDs decrease IGF-1 levels and, thus, reduce cancer growth in carcinomas such as the pancreas, colon, liver, and prostate. However, other studies have shed light on the potential of the receptor as a biomarker for uroepithelial carcinomas, particularly due to its stimulatory effect on migration of bladder cancer cells. Furthermore, PPARγmay provide the tumor-promoting microenvironment by de novo synthesis of nutrients that are needed for bladder cancer development. In this review, we closely examine the TZD class of drugs and their effects on PPARγin patient studies along with additional molecular factors that are positive modulators, such as protein phosphatase 5 (PP5), which may have considerable implications for bladder cancer therapy.
authors.affiliation: Center for Hypertension and Personalized Medicine, Department of Physiology & Pharmacology, University of Toledo College of Medicine, Toledo, OH 43614, USA.
authors.forename: Melody
authors.initials: M
authors.lastname: Chiu
authors.affiliation: Center for Hypertension and Personalized Medicine, Department of Physiology & Pharmacology, University of Toledo College of Medicine, Toledo, OH 43614, USA.
authors.forename: Lucien
authors.initials: L
authors.lastname: McBeth
authors.affiliation: Department of Urology, University of Toledo College of Medicine, Toledo, OH 43614, USA.
authors.forename: Puneet
authors.initials: P
authors.lastname: Sindhwani
authors.affiliation: Center for Hypertension and Personalized Medicine, Department of Physiology & Pharmacology, University of Toledo College of Medicine, Toledo, OH 43614, USA; Department of Urology, University of Toledo College of Medicine, Toledo, OH 43614, USA.
authors.forename: Terry D
authors.identifier: 0000-0002-7599-1529
authors.initials: TD
authors.lastname: Hinds