Journal
JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION
Volume 57, Issue 1, Pages 39-43Publisher
JOURNAL CLINICAL BIOCHEMISTRY & NUTRITION
DOI: 10.3164/jcbn.15-28
Keywords
limonin; Min mice; colon cancer; c-Myc; Tcf/Lef
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Funding
- Ministry of Health, Labour, and Welfare of Japan
- Japan Cancer Society
- National Cancer Center Research Core Facility [23-A-7]
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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 beta-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.
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