JBIC Journal of Biological Inorganic Chemistry

, Volume 22, Issue 5, pp 765–774

Interactions of cisplatin and the copper transporter CTR1 in human colon cancer cells

  • Mia C. Akerfeldt
  • Carmen M.-N. Tran
  • Clara Shen
  • Trevor W. Hambley
  • Elizabeth J. New
Original Paper

DOI: 10.1007/s00775-017-1467-y

Cite this article as:
Akerfeldt, M.C., Tran, C.MN., Shen, C. et al. J Biol Inorg Chem (2017) 22: 765. doi:10.1007/s00775-017-1467-y
Part of the following topical collections:
  1. AsBIC8: 8th Asian Biological Inorganic Chemistry Special Issue

Abstract

There is much interest in understanding the mechanisms by which platinum-based anticancer agents enter cells, and the copper transporter CTR1 has been the focus of many recent studies. While there is a clinical correlation between CTR1 levels and platinum efficacy, cellular studies have provided conflicting evidence relating to the relationship between cisplatin and CTR1. We report here our studies of the relationship between cisplatin and copper homeostasis in human colon cancer cells. While the accumulation of copper and platinum do not appear to compete with each other, we did observe that cisplatin perturbs CTR1 distribution within 10 min, a far shorter incubation time than commonly employed in cellular studies of cisplatin. Furthermore, on these short time-scales, cisplatin caused an increase in the cytoplasmic labile copper pool. While the predominant focus of studies to date has been on CTR1, these studies highlight the importance of investigating the interaction of cisplatin with other copper proteins.

Keywords

Anticancer drug Cisplatin Copper Metal transport 

Abbreviations

Atox1

Antioxidant 1 copper chaperone

CCS

Copper chaperone for superoxide dismutase

Cox17

Copper chaperone for cytochrome C oxidase

CTR1

Copper transporter 1

DLD-1

Human colon adenocarcinoma

DMT1

Divalent metal transporter 1

GF-AAS

Graphite furnace atomic absorption spectroscopy

GFP

Green fluorescent protein

HEK

Human embryonic kidney

ICP-MS

Inductively coupled plasma mass spectrometry

Funding information

Funder NameGrant NumberFunding Note
Australian Research Council
  • DP150103369

Copyright information

© SBIC 2017

Authors and Affiliations

  • Mia C. Akerfeldt
    • 1
  • Carmen M.-N. Tran
    • 1
  • Clara Shen
    • 1
  • Trevor W. Hambley
    • 1
  • Elizabeth J. New
    • 1
  1. 1.School of ChemistryThe University of SydneySydneyAustralia

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