Peroxisome proliferator-activated receptor modulators as potential chemopreventive agents

Peroxisome proliferator-activated receptors (PPARs), members of the superfamily of nuclear steroid hormone receptors, have traditionally been studied for their role in lipid, glucose, and energy homeostasis. Recent evidence suggests that pharmacological activation of PPARgamma and PPARalpha, and inhibition of PPARdelta, may prevent cancer. PPARgamma agonists induce differentiation, inhibit the growth of established tumor cells in vitro and in vivo, and have chemopreventive effects in animal models. PPARalpha has anti-inflammatory and differentiating activity and protects against the oxidative damage associated with aging. In contrast, PPARdelta expression may be a factor in colorectal carcinogenesis. PPARdelta is normally repressed by the adenomatous polyposis coli tumor suppressor gene, and impaired adenomatous polyposis coli is strongly associated with human colorectal cancer risk. This review presents a rationale for using PPAR modulators as cancer chemopreventive drugs.