Gastroenterology

Gastroenterology

Volume 124, Issue 2, February 2003, Pages 361-367
Gastroenterology

Basic–Alimentary Tract
Peroxisome proliferator-activated receptor γ ligands suppress colon carcinogenesis induced by azoxymethane in mice

https://doi.org/10.1053/gast.2003.50067Get rights and content

Abstract

Background & Aims: Peroxisome proliferator-activated receptor γ (PPARγ) 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 PPARγ 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 PPARγ in carcinogenesis. Tanaka et al.24 have recently reported the suppressive effect of a PPARγ ligand, troglitazone (Tro), on the formation of aberrant crypt foci (ACF) in rats. In the present study, 3 different kinds of PPARγ ligands were subjected to the experiments to confirm their suppressive effects on colon carcinogenesis. Methods: Three PPARγ 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 PPARγ ligand was also examined. Results: PPARγ 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. Conclusions: Our findings indicate that PPARγ ligands are indeed potential chemopreventive agents for colon carcinogenesis.

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Supported in part by the priority research grant from Yokohama City University (to A.N.), a grant (SH44211) from the Human Science foundation (to A.N.), and a grant (Tokuteiryouiki C13204072, to A.N.) from the Ministry of Education, Culture, Sports, Science and Technology, Japan.

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