中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 药理学第一研究室
Chikusetsusaponin IVa Butyl Ester (CS-IVa-Be), a Novel IL6R Antagonist, Inhibits IL6/STAT3 Signaling Pathway and Induces Cancer Cell Apoptosis

文献类型：期刊论文

作者Yang, Jie2,4; Qian, Shihui4; Cai, Xueting2,4; Lu, Wuguang2,4; Hu, Chunping2,4; Sun, Xiaoyan2,4; Yang, Yang2,4; Yu, Qiang3; Gao, S. Paul1; Cao, Peng2,4
刊名MOLECULAR CANCER THERAPEUTICS
出版日期2016-06
卷号15期号:6页码:1190-1200
ISSN号1535-7163
DOI10.1158/1535-7163.MCT-15-0551
文献子类Article
英文摘要The activation of IL6/STAT3 signaling is associated with the pathogenesis of many cancers. Agents that suppress IL6/STAT3 signaling have cancer-therapeutic potential. In this study, we found that chikusetsusaponin IVa butyl ester (CS-IVa-Be), a triterpenoid saponin extracted from Acanthopanas gracilistylus W.W. Smith, induced cancer cell apoptosis. CS-IVa-Be inhibited constitutive and IL6-induced STAT3 activation, repressed STAT3 DNA-binding activity, STAT3 nuclear translocation, IL6-induced STAT3 luciferase reporter activity, IL6-induced STAT3-regulated antiapoptosis gene expression in MDA-MB-231 cells, and IL6-induced TF-1 cell proliferation. Surprisingly, CS-IVa-Be inhibited IL6 family cytokines rather than other cytokines induced STAT3 activation. Further studies indicated that CS-IVa-Be is an antag-onist of IL6 receptor via directly binding to the IL6R alpha with a K-d of 663 +/- 74 nmol/L and the GP130 (IL6R beta) with a K-d of 1,660 +/- 243 nmol/L, interfering with the binding of IL6 to IL6R (IL6R alpha and GP130) in vitro and in cancer cells. The inhibitory effect of CS-IVa-Be on the IL6-IL6R alpha-GP130 interaction was relatively specific as CS-IVa-Be showed higher affinity to IL6R alpha than to LIFR (K-d: 4,910 +/- 1,240 nmol/L) and LeptinR (K-d: 4,990 +/- 915 nmol/L). We next demonstrated that CS-IVa-Be not only directly induced cancer cell apoptosis but also sensitized MDA-MB-231 cells to TRAIL-induced apoptosis via upregulating DR5. Our findings suggest that CS-IVa-Be as a novel IL6R antagonist inhibits IL6/STAT3 signaling pathway and sensitizes the MDA-MB-231 cells to TRAIL-induced cell death. (C) 2016 AACR.
WOS关键词HEPATOCELLULAR-CARCINOMA CELLS ; TRAIL-INDUCED APOPTOSIS ; MESENCHYMAL STEM-CELLS ; BREAST-CANCER ; DOWN-REGULATION ; RHEUMATOID-ARTHRITIS ; RECEPTOR ; STAT3 ; INTERLEUKIN-6 ; ACTIVATION
资助项目Jiangsu Province Funds for Distinguished Young Scientists[BK20140049] ; National Natural Science Foundation of China[81403151] ; National Natural Science Foundation of China[81202576]
WOS研究方向Oncology
语种英语
WOS记录号WOS:000377427600004
出版者AMER ASSOC CANCER RESEARCH
源URL[http://119.78.100.183/handle/2S10ELR8/276026]  
专题药理学第一研究室
通讯作者Cao, Peng
作者单位1.Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, 1275 York Ave, New York, NY 10021 USA
2.Nanjing Univ Chinese Med, Affiliated Hosp Integrated Tradit Chinese & Weste, Nanjing, Jiangsu, Peoples R China;
3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China;
4.Jiangsu Prov Acad Tradit Chinese Med, Lab Cellular & Mol Biol, Nanjing, Jiangsu, Peoples R China;
推荐引用方式
GB/T 7714		 Yang, Jie,Qian, Shihui,Cai, Xueting,et al. Chikusetsusaponin IVa Butyl Ester (CS-IVa-Be), a Novel IL6R Antagonist, Inhibits IL6/STAT3 Signaling Pathway and Induces Cancer Cell Apoptosis[J]. MOLECULAR CANCER THERAPEUTICS,2016,15(6):1190-1200.
APA Yang, Jie.,Qian, Shihui.,Cai, Xueting.,Lu, Wuguang.,Hu, Chunping.,...&Cao, Peng.(2016).Chikusetsusaponin IVa Butyl Ester (CS-IVa-Be), a Novel IL6R Antagonist, Inhibits IL6/STAT3 Signaling Pathway and Induces Cancer Cell Apoptosis.MOLECULAR CANCER THERAPEUTICS,15(6),1190-1200.
MLA Yang, Jie,et al."Chikusetsusaponin IVa Butyl Ester (CS-IVa-Be), a Novel IL6R Antagonist, Inhibits IL6/STAT3 Signaling Pathway and Induces Cancer Cell Apoptosis".MOLECULAR CANCER THERAPEUTICS 15.6(2016):1190-1200.

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。