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[Cancer Research 61, 2424-2428, March 15, 2001]
© 2001 American Association for Cancer Research

Advances in Brief

Ligands for Peroxisome Proliferator-activated Receptors {alpha} and {gamma} Inhibit Chemically Induced Colitis and Formation of Aberrant Crypt Foci in Rats1

Takuji Tanaka2,,3, Hiroyuki Kohno2, Shin-ichiro Yoshitani, Shigeki Takashima, Ataru Okumura, Akira Murakami and Masashi Hosokawa

Departments of Pathology [T. T., H. K.] and General and Gastrointestinal Surgery [S-i. Y., S. T.], Kanazawa Medical University, Ishikawa 920-0293; Department of Endocrinological Metabolism, Anjo Kosei Hospital, Aichi 446-8602 [A. O.]; Department of Biotechnological Science, Faculty of Biology-Oriented Science and Technology, Kinki University, Wakayama 649-6493 [A. M.]; and Graduate School of Fisheries Sciences, Hokkaido University, Hokkaido 041-8611 [M. H.], Japan

The biological role of the peroxisome proliferator-activated receptors (PPARs) in various diseases, including inflammation and cancer, has been highlighted recently. Although PPAR{gamma} ligands have been found to inhibit mammary carcinogenesis in rodents, the effects on colon tumorigenesis are controversial. In the present study, three different experiments were conducted to investigate the modifying effects of PPARs ligands (PPAR{alpha} and PPAR{gamma}) on colitis and an early phase of colitis-related colon carcinogenesis in male F344 rats. In the first experiment, gastric gavage of troglitazone (PPAR{gamma} ligand, 10 or 100 mg/kg body weight) or bezafibrate (PPAR{alpha} ligand, 10 or 100 mg/kg body weight) inhibited colitis induced by dextran sodium sulfate (DSS) and lowered trefoil factor-2 content in colonic mucosa. In the second experiment, dietary administration (0.01 or 0.05% in diet) of troglitazone and bezafibrate for 4 weeks significantly reduced azoxymethane (AOM, two weekly s.c. injections, 20 mg/kg body weight)-induced formation of aberrant crypts foci, which are precursor lesions for colon carcinoma. In the third experiment, dietary administration (0.01% in diet for 6 weeks) of pioglitazone (PPAR{gamma} ligand), troglitazone, and bezafibrate effectively suppressed DSS/AOM-induced ACF. Administration of both ligands significantly reduced cell proliferation activity in colonic mucosa exposed to DSS and AOM. Our results suggest that synthetic PPARs ligands (PPAR{alpha} and PPAR{gamma}) can inhibit the early stages of colon tumorigenesis with or without colitis.




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