Aim: 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 could induce cell differentiation and apoptosis, suggesting a potential application as chemopreventive agents against carcinogenesis. In the present study, 3 different kinds of PPARgamma ligands were subjected to the experiments to confirm their suppressive effects on liver carcinogenesis.
Methods: Three PPARgamma ligands, pioglitazone (Pio) (200 ppm), rosiglitazone (Rosi) (200 ppm), and troglitazone (Tro) (1,000 ppm) were investigated on the induction of the placental form of rat glutathione S-transferase (rGST P) positive foci, a precancerous lesion of the liver, and liver cancer formation using a diethylnitrosamine-induced liver cancer model in Wistar rats, and dose dependency of a PPARgamma ligand was also examined.
Results: PPARgamma ligands reduced the formation of rGST P-positive foci by diethylnitrosamine and induction of liver cancers was also markedly suppressed by a continuous feeding of Pio at 200 ppm.
Conclusion: PPARgamma ligands are potential chemopreventive agents for liver carcinogenesis.