In vitro and in vivo anti-tumor effects of selected platinum(IV) and dinuclear platinum(II) complexes against lung cancer cells

  • Milos Arsenijevic
  • Marija Milovanovic
  • Snezana Jovanovic
  • Natalija Arsenijevic
  • Bojana Simovic Markovic
  • Marina Gazdic
  • Vladislav Volarevic
Original Paper

DOI: 10.1007/s00775-017-1459-y

Cite this article as:
Arsenijevic, M., Milovanovic, M., Jovanovic, S. et al. J Biol Inorg Chem (2017). doi:10.1007/s00775-017-1459-y

Abstract

In the present study, cytotoxic effects of cisplatin, the most usually used chemotherapeutic agent, were compared with new designed platinum(IV) ([PtCl4(en)] (en = ethylenediamine) and [PtCl4(dach)]) (dach = (±)-trans-1,2-diaminocyclohexane) and platinum(II) complexes ([{trans-Pt(NH3)2Cl}2(μ-pyrazine)](ClO4)2 (Pt1), [{trans-Pt(NH3)2Cl}2(μ-4,4′-bipyridyl)](ClO4)2DMF(Pt2),[{trans-Pt(NH3)2Cl}2(μ-1,2-bis(4pyridyl)ethane)](ClO4)2 (Pt3)), in vitro and in vivo against human and murine lung cancer cells, to determine anti-tumor potential of newly synthesized platinum-based drugs in the therapy of lung cancer. Results obtained by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide], Lactate dehydrogenase and Annexin V/Propidium Iodide assays showed that, among all tested complexes, [PtCl4(en)] had the highest cytotoxicity against human and murine lung carcinoma cells in vitro. [PtCl4(en)] showed significantly higher cytotoxicity then cisplatin in all tested concentrations, mainly by inducing apoptosis in lung cancer cells. [PtCl4(en)] was well tolerated in vivo. Clinical signs of [PtCl4(en)]-induced toxicity, such as changes in food, water consumption or body weight, nephrotoxicity or hepatotoxicity was not observed in [PtCl4(en)]-treated mice. [PtCl4(en)] managed to increase presence of CD45+ leukocytes, including F4/80+ macrophages, CD11c+ dendritic cells, CD4+ helper and CD8+ cytotoxic T cells (CTLs) in the lungs, cytotoxic NK, NKT and CTLs in the spleens of tumor bearing mice, resulting with reduction of metastatic lesions in the lungs, indicating its potential to stimulate anti-tumor immune response in vivo. Due to its anti-tumor cytotoxicity, biocompatibility, and potential for stimulation of anti-tumor immune response, [PtCl4(en)] may be a good candidate for further testing in the field of medicinal chemistry.

Keywords

Lung cancer Cytotoxicity Platinum(IV) complexes Platinum(II) complexes 

Copyright information

© SBIC 2017

Authors and Affiliations

  • Milos Arsenijevic
    • 1
  • Marija Milovanovic
    • 2
  • Snezana Jovanovic
    • 3
  • Natalija Arsenijevic
    • 4
  • Bojana Simovic Markovic
    • 2
  • Marina Gazdic
    • 5
  • Vladislav Volarevic
    • 2
  1. 1.Department of Thoracic Surgery, Faculty of Medical SciencesUniversity of KragujevacKragujevacSerbia
  2. 2.Department of Microbiology and Immunology, Faculty of Medical Sciences, Center for Molecular Medicine and Stem Cell ResearchUniversity of KragujevacKragujevacSerbia
  3. 3.Department of Chemistry, Faculty of ScienceUniversity of KragujevacKragujevacSerbia
  4. 4.Department for Preventive and Pediatric Dentistry, Faculty of Medical SciencesUniversity of KragujevacKragujevacSerbia
  5. 5.Department of Genetics, Faculty of Medical SciencesUniversity of KragujevacKragujevacSerbia

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