| RRC ID |
67700
|
| 著者 |
Ohishi K, Toume K, Arai MA, Koyano T, Kowithayakorn T, Mizoguchi T, Itoh M, Ishibashi M.
|
| タイトル |
9-Hydroxycanthin-6-one, a β-Carboline Alkaloid from Eurycoma longifolia, Is the First Wnt Signal Inhibitor through Activation of Glycogen Synthase Kinase 3β without Depending on Casein Kinase 1α.
|
| ジャーナル |
J Nat Prod
|
| Abstract |
Wnt signaling regulates various processes such as cell proliferation, differentiation, and embryo development. However, numerous diseases have been attributed to the aberrant transduction of Wnt signaling. We screened a plant extract library targeting TCF/β-catenin transcriptional modulating activity with a cell-based luciferase assay. Activity-guided fractionation of the MeOH extract of the E. longifolia root led to the isolation of 9-hydroxycanthin-6-one (1). Compound 1 exhibited TCF/β-catenin inhibitory activity. Compound 1 decreased the expression of Wnt signal target genes, mitf and zic2a, in zebrafish embryos. Treatment of SW480 cells with 1 decreased β-catenin and increased phosphorylated β-catenin (Ser 33, 37, Tyr 41) protein levels. The degradation of β-catenin by 1 was suppressed by GSK3β-siRNA, while compound 1 decreased β-catenin even in the presence of CK1α-siRNA. These results suggest that 1 inhibits Wnt signaling through the activation of GSK3β independent of CK1α.
|
| 巻・号 |
78(5)
|
| ページ |
1139-46
|
| 公開日 |
2015-5-22
|
| DOI |
10.1021/acs.jnatprod.5b00153
|
| PMID |
25905468
|
| MeSH |
Animals
Blotting, Western
Carbolines / chemistry
Carbolines / isolation & purification*
Carbolines / pharmacology*
Casein Kinase Ialpha / metabolism*
Eurycoma / chemistry*
Glycogen Synthase Kinase 3 / drug effects
Glycogen Synthase Kinase 3 / metabolism*
Glycogen Synthase Kinase 3 beta
HCT116 Cells
Humans
Indole Alkaloids / chemistry
Indole Alkaloids / isolation & purification*
Indole Alkaloids / pharmacology*
Luciferases / metabolism
Plant Roots / chemistry
Thailand
Wnt Signaling Pathway / drug effects*
Zebrafish
beta Catenin / analysis
beta Catenin / drug effects
|
| IF |
3.782
|
| リソース情報 |
| ヒト・動物細胞 |
293T(RCB2202) |
