Suppression of intestinal carcinogenesis in Apc-mutant mice by limonin

• Published in: Journal of Clinical Biochemistry and Nutrition Vol. 57; no. 1; pp. 39 - 43
• Main Authors: Shimizu, Satomi, Fujimoto, Kyoko, Mutoh, Michihiro, Ozaki, Yoshihiko, Yano, Tomohiro, Nakanishi, Ruri, Onuma, Wakana, Fujii, Gen, Miyamoto, Shingo
• Format: Journal Article
• Language: English
• Published: Japan SOCIETY FOR FREE RADICAL RESEARCH JAPAN 01.07.2015; Japan Science and Technology Agency; the Society for Free Radical Research Japan
• Subjects: c-Myc; Carcinogenesis; colon cancer; limonin; Lymphocytes; Min mice; Original; Tcf/Lef; Tcf/Lef; c-Myc; limonin; colon cancer; Min mice
• ISSN: 0912-0009; 1880-5086
• DOI: 10.3164/jcbn.15-28

Limonoids in citrus fruits are known to possess multiple biological functions, such as anti-proliferative functions in human cancer cell lines. Therefore, we aimed to investigate the suppressive effect of limonin on intestinal polyp development in Apc-mutant Min mice. Five-week-old female Min mice were fed a basal diet or a diet containing 250 or 500 ppm limonin for 8 weeks. The total number of polyps in mice treated with 500 ppm limonin decreased to 74% of the untreated control value. Neoplastic cell proliferation in the polyp parts was assessed by counting PCNA positive cells, and a tendency of reduction was obtained by limonin treatment. Moreover, expression levels of c-Myc and MCP-1 mRNA in the polyp part were reduced by administration of limonin. We finally confirmed the effects of limonin on β-catenin signaling, and found limonin significantly inhibited T-cell factor/lymphocyte enhancer factor-dependent transcriptional activity in a dose-dependent manner in the Caco-2 human colon cancer cell line. Our results suggest that limonin might be a candidate chemopreventive agent against intestinal carcinogenesis.