title: Atractylochromene Is a Repressor of Wnt/β-Catenin Signaling in Colon Cancer Cells.
abstract: Wnt/β-catenin signaling pathway was mutated in about 90% of the sporadic and hereditary colorectal cancers. The abnormally activated β-catenin increases the cancer cell proliferation, differentiation and metastasis through increasing the expression of its oncogenic target genes. In this study, we identified an inhibitor of β-catenin dependent Wnt pathway from rhizomes of Atractylodes macrocephala Koidzumi (Compositae). The active compound was purified by activity-guided purification and the structure was identified as 2,8-dimethyl-6-hydroxy-2-(4-methyl-3-pentenyl)-2H-chromene (atractylochromene, AC). AC suppressed β-catenin/T-cell factor transcriptional activity of HEK-293 reporter cells when they were stimulated by Wnt3a or inhibitor of glycogen synthase kinase-3β. AC down-regulated the nuclear level of β-catenin through the suppression of galectin-3 mediated nuclear translocation of β-catenin in SW-480 colon cancer cells. Furthermore, AC inhibits proliferation of colon cancer cell. Taken together, AC from A. macrocephala might be a potential chemotherapeutic agent for the prevention and treatment of human colon cancer.
authors.affiliation: Research Center for Cell Fate Control and College of Pharmacy, Sookmyung Women's University, Seoul 140-742.
authors.forename: Ah-Ram
authors.initials: AR
authors.lastname: Shim
authors.affiliation: Research Center for Cell Fate Control and College of Pharmacy, Sookmyung Women's University, Seoul 140-742.
authors.forename: Guang-Zhi
authors.initials: GZ
authors.lastname: Dong
authors.affiliation: Department of Natural Medicine Resources, Semyung University, Jecheon 390-711, Republic of Korea.
authors.forename: Hwa Jin
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Research Center for Cell Fate Control and College of Pharmacy, Sookmyung Women's University, Seoul 140-742.
authors.forename: Jae-Ha
authors.initials: JH
authors.lastname: Ryu
keywords: Atractylochromene; Colon cancer; Proliferation; Wnt/β-catenin