論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | 293T(RCB2202) |