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Investigations of cellular copper metabolism in ovarian cancer cells using a ratiometric fluorescent copper dye

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Abstract

Imbalances in metal homeostasis have been implicated in the progression and drug response of cancer cells. Understanding these changes will enable identification of new treatment regimes and precision medicine approaches to cancer treatment. In particular, there has been considerable interest in the interplay between copper homeostasis and response to platinum-based chemotherapeutic agents. Here, we have studied differences in the Cu uptake and distributions in the ovarian cancer cell line, A2780, and its cisplatin resistant form, A2780.CisR, by measuring total Cu content and the bioavailable Cu pool. Atomic absorption spectroscopy (AAS) revealed a lower total Cu uptake in A2780.CisR compared to A2780 cells. Conversely, live-cell confocal microscopy studies with the ratiometric Cu(I)-sensitive fluorescent dye, InCCu1, revealed higher relative cellular content of labile Cu in A2780.CisR cells compared with A2780 cells. These results demonstrate that Cu trafficking, homeostasis and speciation are different in the Pt-sensitive and resistant cells and may be associated with the predominance of different phenotypes for A2780 (epithelial) and A2780.CisR (mesenchymal) cells.

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Data availability

Original data for this article are available on request from aviva.levina@sydney.edu.au.

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Acknowledgements

We are grateful for Australian Centre for Microscopy and Microanalysis (ACMM) especially Dr Gerald Shami and Dr Yingying Su for assistance with cell culture and confocal microscopy, Bosch Molecular Biology facility at the University of Sydney for IncuCyte experiments, Em. Prof. Trevor W. Hambley for providing A2780 and A2780.CisR cells, Dr Clara Shen for providing InCCu1 probe, Dr Jia Hao Yeo for confocal microscopy training, and Dr Nicholas Proschogo for ICP-MS measurements.

Funding

We are grateful for financial supported by Australian Research Council (ARC, DP160104172), that helped fund this research and to the Chemistry Department, Jazan University, Kingdom of Saudi Arabia for a PhD scholarship (SMA).

Author information

Authors and Affiliations

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

    Sumayah Mohammed Asiri, Aviva Levina, Elizabeth J. New & Peter A. Lay

  2. The University of Sydney Nano Institute (Sydney Nano), The University of Sydney, Sydney, NSW, 2006, Australia

    Elizabeth J. New

  3. Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Sydney, Sydney, NSW, 2006, Australia

    Elizabeth J. New

  4. Sydney Analytical, The University of Sydney, Sydney, NSW, 2006, Australia

    Peter A. Lay

Authors
  1. Sumayah Mohammed Asiri
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  2. Aviva Levina
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  3. Elizabeth J. New
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  4. Peter A. Lay
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Correspondence to Elizabeth J. New or Peter A. Lay.

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Mohammed Asiri, S., Levina, A., New, E.J. et al. Investigations of cellular copper metabolism in ovarian cancer cells using a ratiometric fluorescent copper dye. J Biol Inorg Chem 28, 43–55 (2023). https://doi.org/10.1007/s00775-022-01978-9

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