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Inhibition of human copper trafficking by a small molecule significantly attenuates cancer cell proliferation

文献类型：期刊论文

作者Wang, Jing1,2; Luo, Cheng3; Shan, Changliang4; You, Qiancheng1,2; Lu, Junyan3; Elf, Shannon4; Zhou, Yu3; Wen, Yi3; Vinkenborg, Jan L.5; Fan, Jun4
刊名NATURE CHEMISTRY
出版日期2015-12
卷号7期号:12页码:968-979
ISSN号1755-4330
DOI10.1038/NCHEM.2381
文献子类Article
英文摘要Copper is a transition metal that plays critical roles in many life processes. Controlling the cellular concentration and trafficking of copper offers a route to disrupt these processes. Here we report small molecules that inhibit the human copper-trafficking proteins Atox1 and CCS, and so provide a selective approach to disrupt cellular copper transport. The knockdown of Atox1 and CCS or their inhibition leads to a significantly reduced proliferation of cancer cells, but not of normal cells, as well as to attenuated tumour growth in mouse models. We show that blocking copper trafficking induces cellular oxidative stress and reduces levels of cellular ATP. The reduced level of ATP results in activation of the AMP-activated protein kinase that leads to reduced lipogenesis. Both effects contribute to the inhibition of cancer cell proliferation. Our results establish copper chaperones as new targets for future developments in anticancer therapies.
WOS关键词SUPEROXIDE-DISMUTASE ; ANTICANCER STRATEGY ; OXIDATIVE STRESS ; METALLOCHAPERONE ; METABOLISM ; CHAPERONE ; HOMEOSTASIS ; MECHANISMS ; DISEASE ; TARGET
资助项目National Natural Science Foundation of China[21210003] ; National Natural Science Foundation of China[81230076] ; National Natural Science Foundation of China[91313000] ; Hi-Tech Research and Development Program of China[2012AA020302] ; Hi-Tech Research and Development Program of China[2012AA01A305] ; Chinese Academy of Sciences[XDA01040305] ; National Science Foundation[CHE-1213598] ; National Institutes of Health[CA140515] ; Howard Hughes Medical Institute[00000000]
WOS研究方向Chemistry
语种英语
出版者NATURE PUBLISHING GROUP
WOS记录号WOS:000365279200010
源URL[http://119.78.100.183/handle/2S10ELR8/276313]  
专题药物发现与设计中心
中科院受体结构与功能重点实验室
新药研究国家重点实验室
分析化学研究室
药物化学研究室
药理学第一研究室
通讯作者Wang, Jing
作者单位1.Univ Chicago, Howard Hughes Med Inst, Chicago, IL 60637 USA
2.Univ Chicago, Inst Biophys Dynam, Dept Biochem & Mol Biol, Dept Chem, Chicago, IL 60637 USA;
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China;
4.Emory Univ, Sch Med, Winship Canc Inst, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA;
5.Eindhoven Univ Technol, Biol Chem Lab, NL-5600 MB Eindhoven, Netherlands;
6.Northwestern Univ, Dept Mol BioSci, Evanston, IL 60208 USA;
推荐引用方式
GB/T 7714		 Wang, Jing,Luo, Cheng,Shan, Changliang,et al. Inhibition of human copper trafficking by a small molecule significantly attenuates cancer cell proliferation[J]. NATURE CHEMISTRY,2015,7(12):968-979.
APA Wang, Jing.,Luo, Cheng.,Shan, Changliang.,You, Qiancheng.,Lu, Junyan.,...&He, Chuan.(2015).Inhibition of human copper trafficking by a small molecule significantly attenuates cancer cell proliferation.NATURE CHEMISTRY,7(12),968-979.
MLA Wang, Jing,et al."Inhibition of human copper trafficking by a small molecule significantly attenuates cancer cell proliferation".NATURE CHEMISTRY 7.12(2015):968-979.

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来源：上海药物研究所

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