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Peroxisome Proliferator-activated Receptor Modulators As Potential Chemopreventive Agents
National Cancer Institute, Division of Cancer Prevention, Bethesda, Maryland 20892-7322 [L. K., J. R. F., J. A. C.] Department of Pharmacology, Georgetown University School of Medicine, Washington, D.C. 20057 [R. I. G.]
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 PPAR
and PPAR
, and inhibition of PPAR
, may prevent cancer. PPAR agonists induce differentiation, inhibit the growth of established tumor cells in vitro and in vivo, and have chemopreventive effects in animal models. PPAR has anti-inflammatory and differentiating activity and protects against the oxidative damage associated with aging. In contrast, PPAR expression may be a factor in colorectal carcinogenesis. PPAR 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.
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