• Molecular pharmacology · Sep 2006

    Hexachlorophene inhibits Wnt/beta-catenin pathway by promoting Siah-mediated beta-catenin degradation.

    • Seoyoung Park, Jungsug Gwak, Munju Cho, Taeyun Song, Jaejoon Won, Dong-Eun Kim, Jae-Gook Shin, and Sangtaek Oh.
    • PharmcoGenomics Research Center, Inje University, Busan 614-735, Korea.
    • Mol. Pharmacol. 2006 Sep 1; 70 (3): 960-6.

    AbstractAberrant activation of Wnt/beta-catenin signaling and subsequent up-regulation of beta-catenin response transcription (CRT) is a critical event in the development of human colon cancer. Thus, Wnt/beta-catenin signaling is an attractive target for the development of anticancer therapeutics. In this study, we identified hexachlorophene as an inhibitor of Wnt/beta-catenin signaling from cell-based small-molecule screening. Hexachlorophene antagonized CRT that was stimulated by Wnt3a-conditioned medium by promoting the degradation of beta-catenin. This degradation pathway is Siah-1 and adenomatous polyposis colidependent, but glycogen synthase kinase-3beta and F-box beta-transducin repeat-containing protein-independent. In addition, hexachlorophene represses the expression of cyclin D1, which is a known beta-catenin target gene, and inhibits the growth of colon cancer cells. Our findings suggest that hexachlorophene attenuates Wnt/beta-catenin signaling through the Siah-1-mediated beta-catenin degradation.

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