Peroxisome proliferator-activated receptor gamma and cancers.

Abstract

The peroxisome proliferator-activated receptor gamma (PPARgamma) ligands have anticancer activity against a wide variety of neoplastic cells in vitro. Animal studies have chronicled their in vivo anticancer effects and chemopreventive capabilities. In addition, moderate anticancer activities of PPARgamma ligands with minimal toxicities have been observed in patients with liposarcomas and prostate cancers. These compounds can slow growth and induce partial differentiation of selected cancer cells. They can decrease levels of cyclin D(1) and E, inflammatory cytokines, and nuclear factor kappaB and increase expression of p21(waf1) and p27(kip1). Surprisingly, some or many of these effects may occur independently of PPARgamma. Other data suggest that PPARgamma may behave as a tumor suppressor gene, although several compelling murine models, paradoxically, suggest that under selected circumstances, PPARgamma ligands may stimulate cancer formation. Nevertheless, the bulk of studies showed that PPARgamma ligands do have antiproliferative activity against many transformed cells and may be helpful in the setting of adjuvant and chemopreventive treatments of several common tumors, including colon, prostate, and breast cancers.