17-Hydroxy-jolkinolide B Inhibits Signal Transducers and Activators of Transcription 3 Signaling by Covalently Cross-Linking Janus Kinases and Induces Apoptosis of Human Cancer Cells
文献类型：期刊论文
| 作者 | Wang, Ying2; Ma, Xiuquan1; Yan, Shousheng2; Shen, Shensi2; Zhu, Huiling2; Gu, Yuan2; Wang, Hongbing3; Qin, Guowei3; Yu, Qiang2
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| 刊名 | CANCER RESEARCH
 |
| 出版日期 | 2009-09-15 |
| 卷号 | 69期号:18页码:7302-7310 |
| ISSN号 | 0008-5472 |
| DOI | 10.1158/0008-5472.CAN-09-0462 |
| 文献子类 | Article |
| 英文摘要 | Constitutive activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway occurs frequently in cancer cells and contributes to oncogenesis. Among the members of STAT family, STAT3 plays a pivotal role in the development and progression of human tumors. The STAT3-mediated signaling pathway has been recognized as a promising anticancer target. Here, we show that 17-Hydroxy-jolkinolide B (HJB), a diterpenoid from the Chinese medicinal herb Euphorbia fischeriana Steud, strongly inhibits interleukin (IL)-6-induced as well as constitutive STAT3 activation. Furthermore, we show that HJB directly targets the JAK family kinases, JAK1, JAK2, and TYK2, by inducing dimerization of the JAKs via cross-linking. Addition of DTT or glutathione prevents the JAK cross-inking and blocks the inhibitory effects of BJB on IL-6-induced STAT3 activation, suggesting that HJB may react with cystein residues of JAKs to form covalent bonds that inactivate JAKs. Liquid chromatography/mass spectrometry analysis confirmed that each HJB reacted with two thiols. The effect of HJB on the JAK/STAT3 pathway is specific as HJB has no effect on platelet-derived growth factor, epidermal growth factor, or insulin-like growth factor I signaling pathways. Finally, we show that HJB inhibits growth and induces apoptosis of tumor cells, particularly those tumor cells with constitutively activated STAT3. We propose that the natural compound HJB is a promising anticancer drug candidate as a potent STAT3 signaling inhibitor. [Cancer Res 2009;69(18):7302-10] |
| WOS关键词 | IL-6-INDUCED STAT3 ACTIVATION ; POTENT ANTITUMOR-ACTIVITY ; CONSTITUTIVE ACTIVATION ; TYROSINE KINASES ; MYELOMA CELLS ; TUMOR-CELLS ; EUPHORBIA-FISCHERIANA ; POLYCYTHEMIA-VERA ; MULTIPLE-MYELOMA ; JAK/STAT PATHWAY |
| 资助项目 | China National Natural Science Foundation[90713029] ; Shanghai Science and Technology Research[08DZ1971403] ; China Ministry of Science and Technology Research[2008ZX10002-020] |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000269954000024 |
| 出版者 | AMER ASSOC CANCER RESEARCH |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279131]  |
| 专题 | 药理学第一研究室 药物化学研究室 |
| 通讯作者 | Yu, Qiang |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Organ Chem, Dept Bioorgan Chem, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Pharmacol, Shanghai 201203, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Nat Prod Chem, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Wang, Ying,Ma, Xiuquan,Yan, Shousheng,et al. 17-Hydroxy-jolkinolide B Inhibits Signal Transducers and Activators of Transcription 3 Signaling by Covalently Cross-Linking Janus Kinases and Induces Apoptosis of Human Cancer Cells[J]. CANCER RESEARCH,2009,69(18):7302-7310. |
| APA | Wang, Ying.,Ma, Xiuquan.,Yan, Shousheng.,Shen, Shensi.,Zhu, Huiling.,...&Yu, Qiang.(2009).17-Hydroxy-jolkinolide B Inhibits Signal Transducers and Activators of Transcription 3 Signaling by Covalently Cross-Linking Janus Kinases and Induces Apoptosis of Human Cancer Cells.CANCER RESEARCH,69(18),7302-7310. |
| MLA | Wang, Ying,et al."17-Hydroxy-jolkinolide B Inhibits Signal Transducers and Activators of Transcription 3 Signaling by Covalently Cross-Linking Janus Kinases and Induces Apoptosis of Human Cancer Cells".CANCER RESEARCH 69.18(2009):7302-7310. |
入库方式： OAI收割
来源：上海药物研究所
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