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Ref Type Journal Article
PMID (21321609)
Authors Wang W, Liu H, Wang S, Hao X, Li L
Title A diterpenoid derivative 15-oxospiramilactone inhibits Wnt/β-catenin signaling and colon cancer cell tumorigenesis.
Abstract Text The Wnt/β-catenin signaling pathway is a highly conserved pathway in organism evolution and regulates many biological processes. Aberrant activation of the Wnt/β-catenin signaling pathway is closely related to tumorigenesis. In order to identify potent small molecules to treat the over-activated Wnt signaling-mediated cancer, such as colon cancer, we established a mammalian cell line-based reporter gene screening system. The screen revealed a diterpenoid derivative, 15-oxospiramilactone (NC043) that inhibits Wnt3a or LiCl-stimulated Top-flash reporter activity in HEK293T cells and growth of colon cancer cells, SW480 and Caco-2. Treatment of SW480 cells with NC043 led to decreases in the mRNA and/or protein expression of Wnt target genes Axin2, Cyclin D1 and Survivin , as well as decreases in the protein levels of Cdc25c and Cdc2. NC043 did not affect the cytosol-nuclear distribution and protein level of soluble β-catenin, but decreased β-catenin/TCF4 association in SW480 cells. Moreover, NC043 inhibited anchorage-independent growth and xenograft tumorigenesis of SW480 cells. Collectively these results demonstrate that NC043 is a novel small molecule that inhibits canonical Wnt signaling downstream of β-catenin stability and may be a potential compound for treating colorectal cancer.


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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
NC043 NC043 1 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
NC043 CTNNB1 Inhibitor 27 NC043 inhibits the interaction of CTNNB1 with TCF7L2 to block Wnt signaling resulting in apoptosis and interruption of the cell cycle (PMID: 21321609, PMID: 30774387).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
APC inact mut colorectal cancer sensitive NC043 Preclinical - Cell line xenograft Actionable In a preclinical study, NC043 inhibited Wnt pathway activation and growth of colorectal cancer cell lines harboring APC truncation mutations in culture and in cell line xenograft models (PMID: 21321609). 21321609