Peroxisome Proliferator-Activated Receptor γ Pathway Targeting in Carcinogenesis: Implications for Chemoprevention
- Authors' Affiliation: Department of Otolaryngology and University of Minnesota Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota
- Requests for reprints:
Frank Ondrey, Department of Otolaryngology and University of Minnesota Masonic Cancer Center, University of Minnesota, 410 Delaware Street Southeast, MMC396, Minneapolis, MN 55455. Phone: 612-625-9449; Fax: 612-625-2101; E-mail: ondre002{at}umn.edu.
Abstract
The peroxisome proliferator-activated receptor (PPAR) γ is one member of the nuclear receptor superfamily that contains in excess of 80 described receptors. PPARγ activators are a diverse group of agents that range from endogenous fatty acids or derivatives (linolenic, linoleic, and 15-deoxy-Δ12,14-prostaglandin J2) to Food and Drug Administration-approved thiazolidinedione drugs [pioglitazone (Actos) and rosiglitazone (Avandia)] for the treatment of diabetes. Once activated, PPARγ will preferentially bind with retinoid X receptor α and signal antiproliferative, antiangiogenic, and prodifferentiation pathways in several tissue types, thus making it a highly useful target for down-regulation of carcinogenesis. Although PPAR-γ activators show many anticancer effects on cell lines, their advancement into human advanced cancer clinical trials has met with limited success. This article will review translational findings in PPARγ activation and targeting in carcinogenesis prevention as they relate to the potential use of PPARγ activators clinically as cancer chemoprevention strategies.
Footnotes
-
↵1 Margolis RN, Evans RM, O'Malley BW, NURSA Atlas Consortium. The Nuclear Receptor Signaling Atlas: development of a functional atlas of nuclear receptors. Mol Endocrinol 2005;19:2433–6.
-
↵2 Yang X, Downes M, Yu RT, et al. Nuclear receptor expression links the circadian clock to metabolism. Cell 2006;126:801–10.
-
↵3 Unpublished data.
-
↵4 www.clinicaltrials.gov NCT00408434.
-
↵6 Unpublished data.
-
- Accepted August 11, 2008.
- Received April 23, 2008.
- Revision received August 3, 2008.
