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Platinum(II)-oxalato complexes of seliciclib (CYC202) derivatives show different cellular effects and lesser adverse effects in mouse lymphoma model than cisplatin

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Abstract

This work presents a deeper pharmacological evaluation of two formerly prepared and characterized, and highly in vitro cytotoxic platinum(II) oxalato complexes [Pt(ox)(L1)2] (1) and [Pt(ox)(L2)2] (2), containing the derivatives of cyclin-dependent kinase inhibitor (CDKi) seliciclib ((R)-roscovitine, CYC202) coordinating as N-donor carrier ligands, i.e., 2-(1-ethyl-2-hydroxyethylamino)-N6-(4-methoxybenzyl)-9-isopropyladenine (L1) and 2-chloro-N6-(2,4-dimethoxybenzyl)-9-isopropyladenine (L2). The positive results of in vitro cytotoxicity screening on human cancer cell lines (HeLa, HOS, A2780, A2780R, G361 and MCF7 with IC50 at low micromolar levels) published previously, motivated us to perform extended preclinical in vitro experiments to reveal the mechanisms associated with the induction of cancer cell death. In addition, the in vivo antitumor activity was evaluated using the mouse lymphocytic leukaemia L1210 model. The obtained results revealed that complex 1 exceeds the antitumor effect of cisplatin (as for the extension of life-span of mice) and shows far less adverse effects as compared to reference drug cisplatin. The in vitro and ex vivo studies of cellular effects and molecular mechanisms of cell death induction showed that the mechanism of action of complex 1 is essentially different from that of cisplatin. The obtained results showed a possible way how to obtain antitumor active platinum(II) oxalato complexes with better therapeutic profile than contemporary used platinum-based therapeutics.

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Abbreviations

Casp:

Caspase

CDK:

Cyclin-dependent kinase

CDKi:

Cyclin-dependent kinase inhibitor

PBS:

Phosphate-buffered saline

PI:

Propidium iodide

Ctrl:

Control

References

  1. Kelland L (2007) Nat Rev Cancer 7:573–584. https://doi.org/10.1038/nrc2167

    Article  CAS  PubMed  Google Scholar 

  2. Štarha P, Trávníček Z, Popa I (2010) J Inorg Biochem 104:639–647. https://doi.org/10.1016/j.jinorgbio.2010.02.005

    Article  CAS  PubMed  Google Scholar 

  3. Trávníček Z, Štarha P, Popa I, Vrzal R, Dvořák Z (2010) Eur J Med Chem 45:4609–4614. https://doi.org/10.1016/j.ejmech.2010.07.025

    Article  CAS  PubMed  Google Scholar 

  4. Vrzal R, Štarha P, Dvořák Z, Trávníček Z (2010) J Inorg Biochem 104:1130–1132. https://doi.org/10.1016/j.jinorgbio.2010.07.002

    Article  CAS  PubMed  Google Scholar 

  5. Raymond E, Faivre S, Chaney S, Woynarowski J, Cvitkovic E (2002) Mol Cancer Ther 1:227–235

    CAS  PubMed  Google Scholar 

  6. Štarha P, Hošek J, Vančo J, Dvořák Z, Suchý P, Popa I, Pražanová G, Trávníček Z (2014) PLoS One 9:e90341. https://doi.org/10.1371/journal.pone.0090341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Trávníček Z, Matiková-Maľarová M, Novotná R, Vančo J, Štěpánková K, Suchý P (2011) J Inorg Biochem 105:937–948. https://doi.org/10.1016/j.jinorgbio.2011.04.002

    Article  CAS  PubMed  Google Scholar 

  8. Nair BC, Vallabhaneni S, Tekmal RR, Vadlamudi RK (2011) Breast Cancer Res 13:R80. https://doi.org/10.1186/bcr2929

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. William-Faltaos S, Rouillard D, Lechat P, Bastian G (2006) Anticancer Res 26:2093–2099

    CAS  PubMed  Google Scholar 

  10. Noji M, Kizu R, Takeda Y, Akiyama N, Yoshizaki I, Eriguchi M, Kidani Y (2005) Biomed Pharmacother 59:224–229. https://doi.org/10.1016/j.biopha.2004.06.006

    Article  CAS  PubMed  Google Scholar 

  11. Porter AG, Jänicke RU (1999) Cell Death Differ 6:99–104. https://doi.org/10.1038/sj.cdd.4400476

    Article  CAS  PubMed  Google Scholar 

  12. Dasari S, Tchounwou PB (2014) Eur J Pharmacol 740:364–378. https://doi.org/10.1016/j.ejphar.2014.07.025

    Article  CAS  PubMed  Google Scholar 

  13. Zajac J, Kostrhunova H, Novohradsky V, Vrana O, Raveendran R, Gibson D, Kasparkova J, Brabec V (2016) J Inorg Biochem 156:89–97. https://doi.org/10.1016/j.jinorgbio.2015.12.003

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors thank Dr. Kateřina Kubešová for preparation of the cell pellets for the flow cytometry studies, Dr. Pawel Jewula for performing flow cytometry experiments, and Ms. Gabriela Pražanová for performing a part of immunohistochemical evaluations. This research was funded by the Ministry of Education, Youth and Sports of the Czech Republic (project LO1305).

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Authors and Affiliations

  1. Division of Biologically Active Complexes and Molecular Magnets, Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacký University in Olomouc, Šlechtitelů 27, 783 71, Olomouc, Czech Republic

    Ján Vančo, Pavel Štarha, Jan Hošek & Zdeněk Trávníček

  2. Department of Human Pharmacology and Toxicology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Palackého třída 1946/1, 612 42, Brno, Czech Republic

    Marta Chalupová & Pavel Suchý Jr.

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  1. Ján Vančo
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  2. Pavel Štarha
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  3. Jan Hošek
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  6. Zdeněk Trávníček
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Correspondence to Zdeněk Trávníček.

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Vančo, J., Štarha, P., Hošek, J. et al. Platinum(II)-oxalato complexes of seliciclib (CYC202) derivatives show different cellular effects and lesser adverse effects in mouse lymphoma model than cisplatin. J Biol Inorg Chem 25, 67–73 (2020). https://doi.org/10.1007/s00775-019-01735-5

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  • DOI: https://doi.org/10.1007/s00775-019-01735-5

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