LGH00031, a novel ortho-quinonoid inhibitor of cell division cycle 25B, inhibits human cancer cells via ROS generation
文献类型：期刊论文
| 作者 | Zhou, Yu-bo ; Feng, Xu; Wang, Li-na; Du, Jun-qing; Zhou, Yue-yang; Yu, Hai-ping; Zang, Yi; Li, Jing-ya; Li, Jia
|
| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2009-09 |
| 卷号 | 30期号:9页码:1359-1368 |
| 关键词 | LGH00031 ortho-quinone CDC25B irreversible inhibitor ROS |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2009.131 |
| 文献子类 | Article |
| 英文摘要 | Aim: To discover novel cell division cycle 25 (CDC25) B inhibitors and elucidate the mechanisms of inhibition in cancer cells. Methods: Cell growth inhibition was detected by MTT assay, the cell cycle was analyzed by flow cytometry, and protein expression and phosphorylation was examined by Western blot analysis. Results: LGH00031 inhibited CDC25B irreversibly in vitro in a dose-dependent manner, and impaired the proliferation of tumor cell lines. In synchronized HeLa cells, LGH00031 delayed the cell cycle progression at the G(2)/M phase. LGH00031 increased cyclin-dependent kinase 1 (CDK1) tyrosine 15 phosphorylation and cyclin B1 protein level. The activity of LGH00031 against CDC25B in vitro relied on the existence of 1,4-dithiothreitol (DTT) or dihydrolipoic acid and oxygen. The oxygen free radical scavenger catalase and superoxide dismutase reduced the inactivation of CDC25 by LGH00031, confirming that reactive oxygen species (ROS) mediate the inactivation process in vitro. LGH00031 accelerated cellular ROS production in a dose-dependent manner, and N-acetyl cysteine (NAC) markedly decreased the ROS production induced by LGH00031. Correspondingly, the LGH00031-induced decrease in cell viability and cell cycle arrest, cyclin B1 protein level, and phosphorylation of CDK1 tyrosine 15 were also rescued by NAC that decreased ROS production. Conclusion: The activity of LGH00031 at the molecular and cellular level is mediated by ROS. |
| WOS关键词 | CDC25 PHOSPHATASES ; TRANSGENIC MICE ; IN-VIVO ; DISCOVERY ; ANALOGS ; SPECIFICITY ; MECHANISM |
| 资助项目 | National Natural Science Foundation of China[30801405] ; Major State Hi-tech Research and Development Program[2006AA02Z315] ; Qi Ming Xing Foundation of Shanghai Ministry of Science and Technology[08QH14005] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:3672212 |
| WOS记录号 | WOS:000269894400019 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279141]  |
| 专题 | 国家新药筛选中心 药物安全性评价中心 |
| 通讯作者 | Li, Jia |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhou, Yu-bo,Feng, Xu,Wang, Li-na,et al. LGH00031, a novel ortho-quinonoid inhibitor of cell division cycle 25B, inhibits human cancer cells via ROS generation[J]. ACTA PHARMACOLOGICA SINICA,2009,30(9):1359-1368. |
| APA | Zhou, Yu-bo.,Feng, Xu.,Wang, Li-na.,Du, Jun-qing.,Zhou, Yue-yang.,...&Li, Jia.(2009).LGH00031, a novel ortho-quinonoid inhibitor of cell division cycle 25B, inhibits human cancer cells via ROS generation.ACTA PHARMACOLOGICA SINICA,30(9),1359-1368. |
| MLA | Zhou, Yu-bo,et al."LGH00031, a novel ortho-quinonoid inhibitor of cell division cycle 25B, inhibits human cancer cells via ROS generation".ACTA PHARMACOLOGICA SINICA 30.9(2009):1359-1368. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。