Peroxisome Proliferator-activated Receptor {gamma} and Cancers

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Peroxisome Proliferator-activated Receptor ${gamma}$ and Cancers¹

H. Phillip Koeffler²

Cedars-Sinai Medical Center/University of California, Los Angeles School of Medicine, Division of Hematology/Oncology, Los Angeles, California 90048

The peroxisome proliferator-activated receptor ${gamma}$ (PPAR ${gamma}$ ) ligandshave anticancer activity against a wide variety of neoplasticcells in vitro. Animal studies have chronicled their in vivoanticancer effects and chemopreventive capabilities. In addition,moderate anticancer activities of PPAR ${gamma}$ ligands with minimaltoxicities have been observed in patients with liposarcomasand prostate cancers. These compounds can slow growth and inducepartial differentiation of selected cancer cells. They can decreaselevels of cyclin D₁ and E, inflammatory cytokines, and nuclearfactor ${kappa}$ B and increase expression of p21^waf1 and p27^kip1. Surprisingly,some or many of these effects may occur independently of PPAR ${gamma}$ .Other data suggest that PPAR ${gamma}$ may behave as a tumor suppressorgene, although several compelling murine models, paradoxically,suggest that under selected circumstances, PPAR ${gamma}$ ligands maystimulate cancer formation. Nevertheless, the bulk of studiesshowed that PPAR ${gamma}$ ligands do have antiproliferative activityagainst many transformed cells and may be helpful in the settingof adjuvant and chemopreventive treatments of several commontumors, including colon, prostate, and breast cancers.

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