Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Atractylochromene Is a Repressor of Wnt/β-Catenin Signaling in Colon Cancer Cells

  • Shim, Ah-Ram (Research Center for Cell Fate Control and College of Pharmacy, Sookmyung Women’s University) ;
  • Dong, Guang-Zhi (Research Center for Cell Fate Control and College of Pharmacy, Sookmyung Women’s University) ;
  • Lee, Hwa Jin (Department of Natural Medicine Resources, Semyung University) ;
  • Ryu, Jae-Ha (Research Center for Cell Fate Control and College of Pharmacy, Sookmyung Women’s University)
  • Received : 2014.08.19
  • Accepted : 2014.10.02
  • Published : 2015.01.01
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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 b-catenin/Tcell 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.

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References

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