論文 - 詳細
| RRC ID | 65583 |
|---|---|
| 著者 | Yonezawa H, Ogawa M, Katayama S, Shimizu Y, Omori N, Oku Y, Sakyo T, Uehara Y, Nishiya N. |
| タイトル | Clotrimazole inhibits the Wnt/β-catenin pathway by activating two eIF2α kinases: The heme-regulated translational inhibitor and the double-stranded RNA-induced protein kinase. |
| ジャーナル | Biochem Biophys Res Commun |
| Abstract |
The Wnt/β-catenin signaling pathway controls cell proliferation and differentiation, and therefore, when this pathway is excessively activated, it causes tumorigenesis. Our chemical suppressor screening in zebrafish embryos identified antifungal azoles including clotrimazole, miconazole, and itraconazole, as Wnt/β-catenin signaling inhibitors. Here we show the mechanism underlying the Wnt/β-catenin pathway inhibition by antifungal azoles. Clotrimazole reduced β-catenin revels in a proteasome-independent fashion. By gene knockdown of two translational regulators, heme-regulated translational inhibitor and double-stranded RNA-induced protein kinase, we show that they mediate the clotrimazole-induced inhibition of the Wnt/β-catenin pathway. Thus, clotrimazole inhibits the Wnt/β-catenin pathway by decreasing β-catenin protein levels through translational regulation. Antifungal azoles represent genuine candidate compounds for anticancer drugs or chemopreventive agents that reduce adenomatous polyps. |
| 巻・号 | 506(1) |
| ページ | 183-188 |
| 公開日 | 2018-11-17 |
| DOI | 10.1016/j.bbrc.2018.10.053 |
| PII | S0006-291X(18)32199-5 |
| PMID | 30342850 |
| MeSH | Animals Antifungal Agents Azoles / pharmacology Clotrimazole / pharmacology* Enzyme Activation / drug effects Gene Knockdown Techniques Humans Protein Biosynthesis / drug effects Protein Biosynthesis / genetics Wnt Signaling Pathway / drug effects* beta Catenin / drug effects beta Catenin / metabolism eIF-2 Kinase / metabolism* |
| IF | 2.985 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 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 | |
| ゼブラフィッシュ | RIKEN WT |