2. Academic Validation
  3. Inhibition of human copper trafficking by a small molecule significantly attenuates cancer cell proliferation

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

  • Nat Chem. 2015 Dec;7(12):968-79. doi: 10.1038/nchem.2381.
Jing Wang 1 2,  Cheng Luo 3,  Changliang Shan 4,  Qiancheng You 1 2,  Junyan Lu 3,  Shannon Elf 4,  Yu Zhou 3,  Yi Wen 3,  Jan L Vinkenborg 5,  Jun Fan 4,  Heebum Kang 4,  Ruiting Lin 4,  Dali Han 1 2,  Yuxin Xie 1 2,  Jason Karpus 1 2,  Shijie Chen 3,  Shisheng Ouyang 3,  Chihao Luan 6,  Naixia Zhang 3,  Hong Ding 3,  Maarten Merkx 5,  Hong Liu 3,  Jing Chen 4,  Hualiang Jiang 3,  Chuan He 1 2
Affiliations

Affiliations

  • 1 Department of Chemistry, Department of Biochemistry and Molecule Biology, Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
  • 2 Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
  • 3 Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • 4 Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
  • 5 Laboratory of Chemical Biology, Eindhoven University of Technology, 5600 MB Eindhoven, Netherlands.
  • 6 Department of Molecular BioSciences, Northwestern University, Evanston, Illinois 60208, USA.
PMID: 26587712 DOI: 10.1038/nchem.2381
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.

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Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-107636
    99.97%, Atox1/CCS Inhibitor