Journal
FOOD AND CHEMICAL TOXICOLOGY
Volume 48, Issue 8-9, Pages 2247-2252Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2010.05.056
Keywords
Lignans; Arctigenin; Arctiin; Matairesinol; Wnt/beta-catenin signaling; Colon cancer
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Funding
- National Research Foundation of Korea (NRF) through Center project for Korea-Mongolia Science and Technology Cooperation
- KIST Gangneung Institute [2Z03411]
- Ministry of Education, Science and Technology (MEST) [2U03920]
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As aberrant activation of Wnt/beta-catenin signaling is one of the major mechanisms of carcinogenesis in colon cancer, identification of inhibitors of this pathway may aid in colon cancer prevention. We investigated the ability of the lignans arctiin, matairesinol and arctigenin from Saussurea salicifolia to inhibit Wnt/beta-catenin signaling in SW480 human colon cancer cells. The lignans inhibited SW480 cell growth. In addition, the transcriptional activity of a reporter construct containing the TCF binding element (TBE) was decreased after the treatment with all three lignans. Although arctiin, matairesinol and arctigenin have similar structures, arctigenin affected Wnt/beta-catenin signaling most significantly. Further, arctigenin reduced the level of beta-catenin by inducing its phosphorylation and thus its degradation. Arctigenin also decreased expression of the beta-catenin/TCF downstream genes CCND1, survivin and CTNNB1, and induced apoptosis. These results suggest that arctigenin, an aglycone with a methoxyl group, potently inhibits the growth of human colon cancer cells via the Wnt/beta-catenin signaling pathway. (C) 2010 Published by Elsevier Ltd.
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