Tussilagone suppresses colon cancer cell proliferation by promoting the degradation of β-catenin.

Abstract

Abnormal activation of the Wnt/β-catenin signaling pathway frequently induces colon cancer progression. In the present study, we identified tussilagone (TSL), a compound isolated from the flower buds of Tussilago farfara, as an inhibitor on β-catenin dependent Wnt pathway. TSL suppressed β-catenin/T-cell factor transcriptional activity and down-regulated β-catenin level both in cytoplasm and nuclei of HEK293 reporter cells when they were stimulated by Wnt3a or activated by an inhibitor of glycogen synthase kinase-3β. Since the mRNA level was not changed by TSL, proteasomal degradation might be responsible for the decreased level of β-catenin. In SW480 and HCT116 colon cancer cell lines, TSL suppressed the β-catenin activity and also decreased the expression of cyclin D1 and c-myc, representative target genes of the Wnt/β-catenin signaling pathway, and consequently inhibited the proliferation of colon cancer cells. Taken together, TSL might be a potential chemotherapeutic agent for the prevention and treatment of human colon cancer.

• Authors: Hua Li, Hwa Jin Lee, Yeon Hwa Ahn, Hye Jin Kwon, Chang-Young Jang, Woo-Young Kim, Jae-Ha Ryu
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 443 Issue 1 Pg. 132-7 (Jan 03 2014) ISSN: 1090-2104 [Electronic] United States
• PMID: 24269588 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Sesquiterpenes
• Wnt Proteins
• beta Catenin
• tussilagone

Topics

• Antineoplastic Agents (pharmacology)
• Cell Proliferation (drug effects)
• Colonic Neoplasms (metabolism, pathology)
• HEK293 Cells
• Humans
• Metabolic Networks and Pathways (drug effects)
• Proteolysis (drug effects)
• Sesquiterpenes (pharmacology)
• Wnt Proteins (antagonists & inhibitors)
• beta Catenin (metabolism)