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

Jing Wang, Cheng Luo, Changliang Shan, Qiancheng You, Junyan Lu, Shannon Elf, Yu Zhou, Yi Wen, Jan L. Vinkenborg, Jun Fan, Heebum Kang, Ruiting Lin, Dali Han, Yuxin Xie, Jason Karpus, Shijie Chen, Shisheng Ouyang, Chihao Luan, Naixia Zhang, Hong DingMaarten Merkx, Hong Liu, Jing Chen, Hualiang Jiang, Chuan He*

*Corresponding author for this work

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)968-979
Number of pages12
JournalNature chemistry
Volume7
Issue number12
DOIs
StatePublished - Dec 1 2015

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

Fingerprint Dive into the research topics of 'Inhibition of human copper trafficking by a small molecule significantly attenuates cancer cell proliferation'. Together they form a unique fingerprint.

Cite this