Tussilagone suppresses colon cancer cell proliferation by promoting the degradation of 尾-catenin
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文摘
Abnormal activation of the Wnt/尾-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 尾-catenin dependent Wnt pathway. TSL suppressed 尾-catenin/T-cell factor transcriptional activity and down-regulated 尾-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尾. Since the mRNA level was not changed by TSL, proteasomal degradation might be responsible for the decreased level of 尾-catenin. In SW480 and HCT116 colon cancer cell lines, TSL suppressed the 尾-catenin activity and also decreased the expression of cyclin D1 and c-myc, representative target genes of the Wnt/尾-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.

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