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KMID : 0606920150230010026
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Biomolecules & Therapeutics
2015 Volume.23 No. 1 p.26 ~ p.30
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Atractylochromene Is a Repressor of Wnt/β-Catenin Signaling in Colon Cancer Cells
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Shim Ah-Ram
Dong Guang Zhi
Lee Hwa-Jin
Ryu Jae-Ha
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Abstract
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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.
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KEYWORD
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Atractylochromene, Wnt/β-catenin, Colon cancer, Proliferation
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