Citrus Compounds Inhibit Inflammation- and Obesity-Related Colon Carcinogenesis in Mice

Abstract

Dietary polyphenols are important potential chemopreventive natural agents. Other agents, such as citrus compounds, are also candidates for cancer chemopreventives. They act on multiple key elements in signal transduction pathways related to cellular proliferation, differentiation, apoptosis, inflammation, and obesity. This short review article provides our findings of preclinical studies on potential chemopreventive activities of dietary citrus compounds, auraptene, collinin, and citrus unshiu segment membrane (CUSM), using clitis- and obesity-related colon tumorigenesis models. Dietary feeding with auraptene and collinin at dose levels of 0.01% and 0.05% significantly lowered the incidence (50–60% reduction) and multiplicity (67–80% reduction) of colonic adenocarcinomas induced by azoxymetahene [AOM, single intraperitoneal injection of 10 mg/kg body weight (bw)] and dextran sodium sulfate (1% in drinking water). Anti-inflammatory potency of aurapene and collinin may contribute to the effects. Administration with CUSM at 3 doses in diet significantly inhibited development of aberrant crypts foci induced by 5 weekly subcutaneous injections of AOM (15 mg/kg bw) in male db/db mice: 53% inhibition by 0.02% CUSM, 54% inhibition by 0.1% CUSM, and 59% inhibition by 0.5% CUSM. CUSM treatment also decreased serum level of triglycerides. Our findings suggest that certain citrus materials are capable of inhibiting clitis- and obesity-related colon carcinogenesis.

ACKNOWLEDGMENTS

This work was supported in part by a Grant-in-Aid for Cancer Research, for the Third-Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labour and Welfare of Japan; a Grant-in-Aid (No. 18592076 to T. Tanaka, 17015016 to T. Tanaka, and 18880030 to Y. Yasui) for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan; and a grant (H2008-12 to T. Tanaka and S2006-9 to Y. Yasui) for the Project Research from the High-Technology Center of Kanazawa Medical University. The authors wish also to thank Dr. Francesco Epifano, PhD (Dipartimento di Scienze del Farmaco, Università “G. D'Annunzio,” Italy) for providing collinin.

Notes

^a Abbreviations are as follows: AOM, azoxymethane; DSS, dextran sodium sulfate.