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

Journal Article · Fri Jan 03 04:00:00 EST 2014 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2013.11.062· OSTI ID:22242240

Li, Hua ^[1]; Lee, Hwa Jin ^[2]; Ahn, Yeon Hwa; Kwon, Hye Jin; Jang, Chang-Young; Kim, Woo-Young ^[1]; Ryu, Jae-Ha ^[1]

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1. College of Pharmacy and Research Center for Cell Fate Control, Sookmyung Women’s University, 52 Hyochangwon-Gil, Yongsan-Gu, Seoul 140-742 (Korea, Republic of)
2. Department of Natural Medicine Resources, Semyung University, 65 Semyung-ro, Jecheon, Chungbuk 390-711 (Korea, Republic of)

Highlights: •Tussilagone (TSL) was purified from plant as an inhibitor of Wnt/β-catenin pathway. •TSL suppressed the β-catenin/T-cell factor transcriptional activity. •The proteasomal degradation of β-catenin was induced by TSL. •TSL suppressed the Wnt/β-catenin target genes, cyclin D1 and c-myc. •TSL inhibit the proliferation of colon cancer cells. -- 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.

• OSTI ID: 22242240
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 443; ISSN BBRCA9; ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CELL PROLIFERATION
CYTOPLASM
GENES
GLYCOGEN
LARGE INTESTINE
MESSENGER-RNA
NEOPLASMS
THERMOLUMINESCENCE