3-Deoxy-2β,16-dihydroxynagilactone E, a natural compound from Podocarpus nagi, preferentially inhibits JAK2/ STAT3 signaling by allosterically interacting with the regulatory domain of JAK2 and induces apoptosis of cancer cells
文献类型：期刊论文
| 作者 | Hui Shan3; Sheng Yao1 ; Yang Ye1; Qiang Yu3
|
| 刊名 | 中国药理学报:英文版
 |
| 出版日期 | 2019 |
| 卷号 | 40.0期号:012页码:1578 |
| 关键词 | JAK/STAT 3-deoxy-2β,16-dihydroxynagilactone E tyrosine kinase inhibitor allosteric inhibitor cancer |
| ISSN号 | 1671-4083 |
| 英文摘要 | The Janus kinase(JAK)/signal transducer and activator of transcription(STAT)pathways,especially the JAK2/STAT3 pathway,play vital roles in the development of many malignancies.Overactivation of STAT3 promotes cancer cell survival and proliferation.Therefore,the JAK2/STAT3-signaling pathway has been considered a promising target for cancer therapy.In this study,we identified a natural compound 3-deoxy-2β,16-dihydroxynagilactone E(B6)from the traditional Chinese medicinal plant Podoajrpus nagi as a potent inhibitor of STAT3 signaling.B6 preferentially inhibited the phosphorylation of STAT3 by interacting with and inactivating JAK2,the main upstream kinase of STAT3.B6 dose-dependently inhibited IL-6-induced STAT3 signaling with an IC50 of 0.2 nM.In contrast to other JAK2 inhibitors,B6 did not interact with the catalytic domain but instead with the FERM-SH2 domain of JAK2.This interaction was JAK-specific since B6 had little effect on other tyrosine kinases.Furthermore,B6 potently inhibited the growth and induced apoptosis of MDA-MB-231 and MDA-MB-468 breast cancer cells with overactivated STAT3.Taken together,our study uncovers a novel compound and a novel mechanism for the regulation of JAK2 and offers a new therapeutic approach for the treatment of cancers with overactivated JAK2/STAT3. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/294580]  |
| 专题 | 新药研究国家重点实验室 |
| 作者单位 | 1.State Key Laboratory of Drug Research and Natural Products Chemistry Department,Shanghai Institute of Materia Medica,Chinese Academy of Sciences 2.中国科学院大学 3.Division of Antitumor Pharmacology,Shanghai Institute of Materia Medica,Chinese Academy of Sciences |
| 推荐引用方式 GB/T 7714 | Hui Shan,Sheng Yao,Yang Ye,et al. 3-Deoxy-2β,16-dihydroxynagilactone E, a natural compound from Podocarpus nagi, preferentially inhibits JAK2/ STAT3 signaling by allosterically interacting with the regulatory domain of JAK2 and induces apoptosis of cancer cells[J]. 中国药理学报:英文版,2019,40.0(012):1578. |
| APA | Hui Shan,Sheng Yao,Yang Ye,&Qiang Yu.(2019).3-Deoxy-2β,16-dihydroxynagilactone E, a natural compound from Podocarpus nagi, preferentially inhibits JAK2/ STAT3 signaling by allosterically interacting with the regulatory domain of JAK2 and induces apoptosis of cancer cells.中国药理学报:英文版,40.0(012),1578. |
| MLA | Hui Shan,et al."3-Deoxy-2β,16-dihydroxynagilactone E, a natural compound from Podocarpus nagi, preferentially inhibits JAK2/ STAT3 signaling by allosterically interacting with the regulatory domain of JAK2 and induces apoptosis of cancer cells".中国药理学报:英文版 40.0.012(2019):1578. |
入库方式： OAI收割
来源：上海药物研究所
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