TY - JOUR T1 - Hexachlorophene Inhibits Wnt/β-Catenin Pathway by Promoting Siah-Mediated β-Catenin Degradation JF - Molecular Pharmacology JO - Mol Pharmacol SP - 960 LP - 966 DO - 10.1124/mol.106.024729 VL - 70 IS - 3 AU - Seoyoung Park AU - Jungsug Gwak AU - Munju Cho AU - Taeyun Song AU - Jaejoon Won AU - Dong-Eun Kim AU - Jae-Gook Shin AU - Sangtaek Oh Y1 - 2006/09/01 UR - http://molpharm.aspetjournals.org/content/70/3/960.abstract N2 - Aberrant activation of Wnt/β-catenin signaling and subsequent up-regulation of β-catenin response transcription (CRT) is a critical event in the development of human colon cancer. Thus, Wnt/β-catenin signaling is an attractive target for the development of anticancer therapeutics. In this study, we identified hexachlorophene as an inhibitor of Wnt/β-catenin signaling from cell-based small-molecule screening. Hexachlorophene antagonized CRT that was stimulated by Wnt3a-conditioned medium by promoting the degradation of β-catenin. This degradation pathway is Siah-1 and adenomatous polyposis colidependent, but glycogen synthase kinase-3β and F-box β-transducin repeat-containing protein-independent. In addition, hexachlorophene represses the expression of cyclin D1, which is a known β-catenin target gene, and inhibits the growth of colon cancer cells. Our findings suggest that hexachlorophene attenuates Wnt/β-catenin signaling through the Siah-1-mediated β-catenin degradation. The American Society for Pharmacology and Experimental Therapeutics ER -