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

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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.

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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

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Acknowledgements

The authors acknowledge the support of the Australian Research Council (TWH and EJN; DP150103369), an Australian Postgraduate Award (CS) and the Westpac Bicentennial Foundation (EJN). We thank Christopher Chang (UC Berkeley) for the provision of CF4, Nicholas Proschogo for assistance with ICP-MS measurements, and acknowledge the scientific and technical assistance of the Australian Microscopy and Microanalysis Research Facility at the Australian Centre for Microscopy and Microanalysis (ACMM) at the University of Sydney.

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Authors and Affiliations

  1. School of Chemistry, The University of Sydney, Sydney, NSW, 2006, Australia

    Mia C. Akerfeldt, Carmen M.-N. Tran, Clara Shen, Trevor W. Hambley & Elizabeth J. New

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  1. Mia C. Akerfeldt
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  2. Carmen M.-N. Tran
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  3. Clara Shen
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  4. Trevor W. Hambley
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  5. Elizabeth J. New
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Correspondence to Elizabeth J. New.

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Akerfeldt, M.C., Tran, C.MN., Shen, C. et al. Interactions of cisplatin and the copper transporter CTR1 in human colon cancer cells. J Biol Inorg Chem 22, 765–774 (2017). https://doi.org/10.1007/s00775-017-1467-y

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  • DOI: https://doi.org/10.1007/s00775-017-1467-y

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