Atractylochromene Is a Repressor of Wnt/beta-Catenin Signaling in Colon Cancer Cells.
10.4062/biomolther.2014.095
- Author:
Ah Ram SHIM
1
;
Guang Zhi DONG
;
Hwa Jin LEE
;
Jae Ha RYU
Author Information
1. Research Center for Cell Fate Control and College of Pharmacy, Sookmyung Women's University, Seoul 140-742, Republic of Korea. ryuha@sookmyung.ac.kr
- Publication Type:Original Article
- Keywords:
Atractylochromene;
Wnt/beta-catenin;
Colon cancer;
Proliferation
- MeSH:
Atractylodes;
beta Catenin;
Cell Proliferation;
Colonic Neoplasms*;
Colorectal Neoplasms;
Galectin 3;
Glycogen Synthase;
Humans;
Neoplasm Metastasis;
Rhizome;
Wnt Signaling Pathway
- From:Biomolecules & Therapeutics
2015;23(1):26-30
- CountryRepublic of Korea
- Language:English
-
Abstract:
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-3beta. 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.
