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

Authors
  • Shimizu, Satomi
  • Miyamoto, Shingo
  • Fujii, Gen
  • Nakanishi, Ruri
  • Onuma, Wakana
  • Ozaki, Yoshihiko
  • Fujimoto, Kyoko
  • Yano, Tomohiro
  • Mutoh, Michihiro
Type
Published Article
Journal
Journal of clinical biochemistry and nutrition
Publication Date
Jul 01, 2015
Volume
57
Issue
1
Pages
39–43
Identifiers
DOI: 10.3164/jcbn.15-28
PMID: 26236099
Source
Medline
Keywords
License
Unknown

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.

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