A perylene derivative regulates HIF-1 alpha and Stat3 signaling pathways
文献类型：期刊论文
| 作者 | Chen, Han1,3; Guan, Yongli1; Yuan, Gu3; Zhang, Qiang3; Jing, Naijie1,2 |
| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY
 |
| 出版日期 | 2014-02-15 |
| 卷号 | 22期号:4页码:1496-1505 |
| 关键词 | Stat3: The Signal Transducer And Activator Of Transcription 3 Hif-1 Alpha: Hypoxia-inducible Factor-1 Alpha Pancreatic Cancer Therapy Breast Cancer Therapy Tel03: a Dual Inhibitor Of Hif-1 Alpha And Stat3 |
| ISSN号 | 0968-0896 |
| DOI | 10.1016/j.bmc.2013.10.018 |
| 英文摘要 | It is becoming increasingly evident that improving the cure rate of many cancers will require treatment regimens hit more than one validated tumor targets. Developing an anti-cancer agent that targets two oncoproteins simultaneously is a promising strategy for accomplishing this goal. It would be expected to promote drug efficacy, reduce therapy-resistant without introducing additional toxic side effects. HIF-1 alpha is a key regulator of the cellular response to hypoxia and is involved in tumor angiogenesis and cancer cell survival, glucose metabolism, and invasion. Stat3 has several oncogenic functions, including suppression of anti-tumor immune responses and promotion of inflammation. Recently, we have identified the perylene derivative, TEL03, as a dual inhibitor that targets both HIF-1 alpha and Stat3. TEL03 blocks the expression of both HIF-1 alpha and Stat3, regulated oncogenes (e. g., Bcl-2, VEGF, Glut1, and others) in cancer cells, and induces cancer cell apoptosis. The results demonstrated that: (i) TEL03 blocks Stat3 phosphorylation, and inhibits Stat3 transcriptional activity; and (ii) interferes the binding of HIF-1 alpha to p300/CBP inducing its degradation by proteasomes under hypoxic conditions. Our in vivo tests showed that as a dual inhibitor, TEL03 dramatically inhibited tumor growth, and provided the evidence that targeting both HIF-1 alpha and Stat3 simultaneously could be a promising strategy for breast and pancreatic cancer therapies. (C) 2014 Published by Elsevier Ltd. |
| 语种 | 英语 |
| WOS记录号 | WOS:000331112900029 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://ir.iccas.ac.cn/handle/121111/52875]  |
| 专题 | 中国科学院化学研究所 |
| 通讯作者 | Chen, Han |
| 作者单位 | 1.Baylor Coll Med, Dept Med, Houston, TX 77030 USA 2.Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA 3.Peking Univ, Coll Chem & Mol Engn, Dept Biol Chem,Beijing Natl Lab Mol Sci, Key Lab Bioorgan Chem & Mol Engn Minist Educ, Beijing 100871, Peoples R China |
| 推荐引用方式 GB/T 7714 | Chen, Han,Guan, Yongli,Yuan, Gu,et al. A perylene derivative regulates HIF-1 alpha and Stat3 signaling pathways[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2014,22(4):1496-1505. |
| APA | Chen, Han,Guan, Yongli,Yuan, Gu,Zhang, Qiang,&Jing, Naijie.(2014).A perylene derivative regulates HIF-1 alpha and Stat3 signaling pathways.BIOORGANIC & MEDICINAL CHEMISTRY,22(4),1496-1505. |
| MLA | Chen, Han,et al."A perylene derivative regulates HIF-1 alpha and Stat3 signaling pathways".BIOORGANIC & MEDICINAL CHEMISTRY 22.4(2014):1496-1505. |
入库方式： OAI收割
来源：化学研究所
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