Citrus Auraptene Suppresses Azoxymethane-Induced Colonic Preneoplastic Lesions in C57BL/KsJ-db/db Mice

Abstract:

The current study was designed to investigate whether dietary citrus auraptene (AUR) suppresses the development of azoxymethane (AOM)-induced colorectal preneoplastic lesions in C57BL/KsJ-db/db (db/db) mice with obese and diabetic phenotypes. Female db/db and wild (+/+) mice were divided into the AOM + AUR, AOM alone, AUR alone, and the untreated groups in each phenotype. AOM was given 3 weekly intraperitoneal injections (10 mg/kg bw). AUR (250 ppm) was given in diet during the study (for 10 wk). Dietary AUR significantly reduced the number of aberrant crypt foci (ACF) and β -catenin-accumulated crypt (BCAC) in both phenotypes. The treatment also lowered cell proliferation activity and increased apoptotic cells in both lesions. Our findings indicate that dietary AUR is able to suppress the early phase of colon carcinogenesis in both phenotypes, suggesting possible application of AUR as a chemopreventive agent in both the high-risk and general populations for colorectal cancer.

Acknowledgments and Notes

We express our thanks to the staff of the Research Animal Facility. This study was supported by the Grant-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare of Japan; the Grant-in-Aid for the 3rd Term for a Comprehensive 10-year Strategy for Cancer Control from the Ministry of Health, Labour and Welfare of Japan; the Grants-in-Aid for Scientific Research (nos. 00120029 and 18592076) from the Ministry of Education, Culture, Sports, Science and Technology of Japan; and the grants (H2006-6 and C2006-3) from Kanazawa Medical University.