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J Clin Biochem Nutr. 2015 Jul;57(1):39-43. doi: 10.3164/jcbn.15-28. Epub 2015 Jun 17.

Suppression of intestinal carcinogenesis in Apc-mutant mice by limonin.

Author information

1
Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan ; Graduate School of Life Sciences, Toyo University, 1-1-1 Izumino, Itakura-machi, Oga-gun, Gunma 374-0193, Japan.
2
Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
3
Faculty of Biology-Oriented Science and Technology, Kinki University, 930 Nishimitani, Kinokawa City, Wakayama 649-6493, Japan.
4
Division of Molecular Biology, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki 859 3298, Japan.
5
Graduate School of Life Sciences, Toyo University, 1-1-1 Izumino, Itakura-machi, Oga-gun, Gunma 374-0193, Japan.

Abstract

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.

KEYWORDS:

Min mice; Tcf/Lef; c-Myc; colon cancer; limonin

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