Atractylochromene Is a Repressor of Wnt/beta-Catenin Signaling in Colon Cancer Cells

作者：Shim Ah Ram; Dong Guang Zhi; Lee Hwa Jin; Ryu Jae Ha^*

来源：Biomolecules & Therapeutics, 2015, 23(1): 26-30.

DOI：10.4062/biomolther.2014.095

• Atractylochromene
• Wnt/beta-catenin
• Colon cancer
• Proliferation

Wnt/beta-catenin signaling pathway was mutated in about 90% of the sporadic and hereditary colorectal cancers. The abnormally activated beta-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 beta-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 beta-catenin/T-cell factor transcriptional activity of HEK-293 reporter cells when they were stimulated by Wnt3a or inhibitor of glycogen synthase kinase-3 beta. AC down-regulated the nuclear level of beta-catenin through the suppression of galectin-3 mediated nuclear translocation of beta-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.

• 出版日期2015-1-1