Troglitazone, a ligand for peroxisome proliferator-activated receptor gamma, inhibits chemically-induced aberrant crypt foci in rats

The biological roles of peroxisome proliferator-activated receptors (PPARs) in various diseases, including inflammation and cancer, have been highligh ted recently, Although PPAR gamma ligand is suspected to play an important role in carcinogenesis, its effects on colon tumorigenesis remain undetermi ned. The present time-course study was conducted to investigate possible mo difying effects of a PPAR gamma ligand, troglitazone, on the development an d growth of aberrant crypt foci (ACF), putative precursor lesions for colon carcinoma, induced by azoxymethane (AOM) or dextran sodium sulfate (DSS) i n male F344 rats. Oral troglitazone (10 or 30 mg/kg body weight (b.w.)) sig nificantly reduced AOM (two weekly subcutaneous injections, 20 mg/kg b.w.)- induced ACF, Treatment with troglitazone increased apoptosis and decreased polyamine content and ornithine decarboxylase (ODC) activity in the colonic mucosa of rats treated with AOM. Gastric gavage of troglitazone also inhib ited colitis and ACF induced by DSS (1% in drinking water), in conjunction with increased apoptosis and reduced colonic mucosal polyamine level and OD C activity. Our results suggest that troglitazone, a synthetic PPAR gamma l igand, can inhibit the early stage of colon tumorigenesis with or without c olitis.