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

Abstract

Abnormal activation of the Wnt/beta-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 beta-catenin dependent Wnt pathway. TSL suppressed beta-catenin/T-cell factor transcriptional activity and down-regulated beta-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-3 beta. Since the mRNA level was not changed by TSL, proteasomal degradation might be responsible for the decreased level of beta-catenin. In SW480 and HCT116 colon cancer cell lines, TSL suppressed the p-catenin activity and also decreased the expression of cyclin D1 and c-myc, representative target genes of the Wnt/beta-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. (C) 2013 Elsevier Inc. All rights reserved.