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The cellular distribution and oxidation state of platinum(II) and platinum(IV) antitumour complexes in cancer cells

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Abstract

The cellular distribution of platinum in A2780 ovarian cancer cells treated with cisplatin and platinum(IV) complexes with a range of reduction potentials has been examined using elemental analysis (synchrotron radiation-induced X-ray emission). The cellular distribution of platinum(IV) drugs after 24 h is similar to that of cisplatin, consistent with the majority of administered platinum(IV) drugs being reduced. Micro-X-ray absorption near-edge spectra of cells treated with cisplatin and platinum(IV) complexes confirmed the reduction of platinum(IV) to platinum(II). In cells treated, the most difficult to reduce complex, cis,trans,cis-[PtCl2(OH)2(NH3)2], platinum(IV) was detected in the cells along with platinum(II). The observations are in accordance with the relative ease of reduction of the platinum(IV) complexes used and support the requirement of reduction for activation of platinum(IV) complexes.

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Abbreviations

en:

ethane-1,2-diamine

GM:

growth medium

PBS:

phosphate buffered saline

RPMI:

Roswell Park Memorial Institute

SRIXE:

synchrotron radiation-induced X-ray emission

XAFS:

X-ray absorption fine structure

XANES:

X-ray absorption near-edge spectroscopy

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Acknowledgements

The authors would like to thank the Australian Research Council and The University of Sydney Cancer Research Fund for financial support. This work was supported by the Australian Synchrotron Research Program, which is funded by the Commonwealth of Australia under the Major National Research Facilities Program. Use of the Advanced Photon Source was supported by the U.S. Department of Energy, Basic Energy Sciences, Office of Energy Research, under contract no. W-31-109-Eng-38. We would like to extend our sincerest thanks to Jacqueline Isaacs of the Department of Anatomy and Histology, The University of Sydney, for preparation of the thin sections, and Professors Peter Lay and Hans Freeman for advice and suggestions.

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Authors and Affiliations

  1. Centre for Heavy Metals Research, School of Chemistry F11, The University of Sydney, 2006, N.S.W. , Australia

    Matthew D. Hall, Carolyn T. Dillon & Trevor W. Hambley

  2. Department of Radiation Oncology, Royal Prince Alfred Hospital, 2050, Camperdown, N.S.W. , Australia

    Mei Zhang

  3. Department of Medical Oncology, Sydney Cancer Centre, Royal Prince Alfred Hospital, 2050, Camperdown, N.S.W. , Australia

    Philip Beale

  4. Experimental Facilities Division, Argonne National Laboratory, Argonne, Il , 60439, USA

    Zhonghou Cai, Barry Lai & Anton P. J. Stampfl

  5. Physics Division, Australian Nuclear Science and Technology Organisation, 2234, Lucas Heights, N.S.W. , Australia

    Anton P. J. Stampfl

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  1. Matthew D. Hall
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  8. Trevor W. Hambley
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Correspondence to Trevor W. Hambley.

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Hall, M.D., Dillon, C.T., Zhang, M. et al. The cellular distribution and oxidation state of platinum(II) and platinum(IV) antitumour complexes in cancer cells. J Biol Inorg Chem 8, 726–732 (2003). https://doi.org/10.1007/s00775-003-0471-6

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  • DOI: https://doi.org/10.1007/s00775-003-0471-6

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