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A fluorescent oxaliplatin derivative for investigation of oxaliplatin resistance using imaging techniques

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Abstract

Oxaliplatin is the backbone of chemotherapy for advanced colorectal cancer and undergoes clinical trials for treatment of other tumour entities. However, acquired resistance is a major hurdle. Confocal microscopy is a useful tool to get an insight into the mechanisms of resistance but it requires fluorescent compounds. This work describes the synthesis of the novel oxaliplatin derivative (CFDA-oxPt) featuring 5(6)-carboxyfluorescein diacetate and evaluation of its applicability for the investigation of oxaliplatin resistance using imaging techniques. CFDA-oxPt was somewhat less cytotoxic than oxaliplatin in sensitive colorectal cancer cells, with EC50 values of 26 and 5.8 µM, respectively. Nevertheless, the potency of the novel complex was significantly decreased to the EC50 of 711.2 µM in oxaliplatin-resistant cells, as was the case for oxaliplatin (EC50 = 81 µM). After incubation, both nuclear and cytosolic localisation was observed. Over time CFDA-oxPt concentrated near the cell membrane and in the vesicular structures, in contrast to the platinum-free label, which was rapidly excreted. These findings suggest that CFDA-oxPt can be used to study oxaliplatin resistance and open the route to new fluorophore-tethered oxaliplatin derivatives.

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Acknowledgements

This work was supported by the Deutsche Forschungsgemeinschaft (JA 817/4-1). The authors are grateful to Prof. Dr. Ulrich Jaehde for helpful discussions and to Prof. Dr. Christa E. Müller for providing laboratory facilities.

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Authors and Affiliations

  1. Department of Clinical Pharmacy, Pharma Centre Bonn, Institute of Pharmacy, University of Bonn, An der Immenburg 4, 53121, Bonn, Germany

    Ganna V. Kalayda & Maximilian Kullmann

  2. Institute of Inorganic Chemistry, University of Vienna, Waehringer Str. 42, 1090, Vienna, Austria

    Mathea Sophia Galanski

  3. Department of Pharmaceutical Chemistry, Pharma Centre Bonn, Institute of Pharmacy, University of Bonn, An der Immenburg 4, 53121, Bonn, Germany

    Sabrina Gollos

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  1. Ganna V. Kalayda
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  2. Maximilian Kullmann
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  4. Sabrina Gollos
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Correspondence to Ganna V. Kalayda.

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Kalayda, G.V., Kullmann, M., Galanski, M. et al. A fluorescent oxaliplatin derivative for investigation of oxaliplatin resistance using imaging techniques. J Biol Inorg Chem 22, 1295–1304 (2017). https://doi.org/10.1007/s00775-017-1502-z

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  • DOI: https://doi.org/10.1007/s00775-017-1502-z

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