Peroxisome proliferator-activated receptor gamma ligands suppress colon carcinogenesis induced by azoxymethane in mice.

Peroxisome proliferator-activated receptor gamma (PPARgamma) is known to regulate growth arrest and terminal differentiation of adipocytes and is used clinically as a new class of antidiabetic drugs. Recently, several studies have reported that treatment of cancer cells with PPARgamma ligands induces cell differentiation and apoptosis, suggesting a potential application as chemopreventive agents against carcinogenesis. However, contradictory results have been reported with regards to the biologic role of PPARgamma in carcinogenesis. Tanaka et al.(24) have recently reported the suppressive effect of a PPARgamma ligand, troglitazone (Tro), on the formation of aberrant crypt foci (ACF) in rats. In the present study, 3 different kinds of PPARgamma ligands were subjected to the experiments to confirm their suppressive effects on colon carcinogenesis. Three PPARgamma ligands, pioglitazone (Pio) (200 ppm), rosiglitazone (Rosi) (200 ppm), and Tro (1000 ppm) were investigated on the induction of ACF, a putative precancerous lesion of the colon, and colon tumor formation using an azoxymethane (AOM)-induced colon cancer model in BALB/c mice, and dose dependency of a PPARgamma ligand was also examined. PPARgamma ligands reduced the ACF formation by AOM (10 mg/kg body weight) and induction of colon tumors were also markedly suppressed by a continuous feeding of Pio at 200 ppm. Our findings indicate that PPARgamma ligands are indeed potential chemopreventive agents for colon carcinogenesis.