論文 - 詳細
| RRC ID | 44392 |
|---|---|
| 著者 | Fukuda Y, Kanbe M, Watanabe M, Dan K, Matsuzaki K, Kitanaka S, Miyata S. |
| タイトル | 3EZ,20Ac-ingenol, a catalytic inhibitor of topoisomerases, downregulates p-Akt and induces DSBs and apoptosis of DT40 cells. |
| ジャーナル | Arch Pharm Res |
| Abstract |
We have previously reported that many ingenol compounds derived from Euphorbia kansui exhibit topoisomerase (topo) II inhibitory activity. Of these compounds, 3EZ,20Ac-ingenol inhibited topo I activity. Camptothecin, which inhibits the religation activity of topo I without interfering with the binding of topo I to DNA and induces topo I-mediated DNA cleavage, was used as a positive control. In this study, we found that 3EZ,20Ac-ingenol did not hamper the binding of topo I to DNA in the same manner as camptothecin but affected the inhibition of cleavage of one DNA strand. 3EZ,20Ac-ingenol inhibited cell proliferation by blocking cell cycle progression in the G2/M phase. To define the mechanism of inhibition of DT40 cell proliferation, the change in Akt activity was observed because Akt activity is regulated in response to DNA damage. Western blot analysis revealed that 3EZ,20Ac-ingenol downregulated the expression of p-Akt, and apoptosis was detected by the presence of DNA double-strand breaks and caspase 3 activation. |
| 巻・号 | 36(8) |
| ページ | 1029-38 |
| 公開日 | 2013-8-1 |
| DOI | 10.1007/s12272-013-0108-4 |
| PMID | 23595550 |
| PMC | PMC3731510 |
| MeSH | Animals Apoptosis / drug effects* Apoptosis / physiology Catalysis Cell Proliferation / drug effects Chickens DNA Breaks, Double-Stranded / drug effects* Diterpenes / chemistry Diterpenes / pharmacology* Dose-Response Relationship, Drug Down-Regulation / drug effects* Down-Regulation / physiology Proto-Oncogene Proteins c-akt / antagonists & inhibitors* Proto-Oncogene Proteins c-akt / metabolism Topoisomerase Inhibitors / chemistry Topoisomerase Inhibitors / pharmacology* |
| IF | 2.934 |
| 引用数 | 7 |
| WOS 分野 | PHARMACOLOGY & PHARMACY CHEMISTRY, MEDICINAL |
| 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 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 2 |
| 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 | DT40(RCB1464) ΔBLM-DT40(RCB1811) ΔWRN-DT40(RCB1812) |