The Journal of Membrane Biology

, Volume 247, Issue 12, pp 1239–1251

Modulation of Activity of Known Cytotoxic Ruthenium(III) Compound (KP418) with Hampered Transmembrane Transport in Electrochemotherapy In Vitro and In Vivo

  • Rosana Hudej
  • Damijan Miklavcic
  • Maja Cemazar
  • Vesna Todorovic
  • Gregor Sersa
  • Alberta Bergamo
  • Gianni Sava
  • Anze Martincic
  • Janez Scancar
  • Bernhard K. Keppler
  • Iztok Turel
Article

Abstract

To increase electrochemotherapy (ECT) applicability, the effectiveness of new drugs is being tested in combination with electroporation. Among them two ruthenium(III) compounds, (imH)[trans-RuCl4(im)(DMSO-S)] (NAMI-A) and Na[trans-RuCl4(ind)2] (KP1339), proved to possess increased antitumor effectiveness when combined with electroporation. The objective of our experimental work was to determine influence of electroporation on the cytotoxic and antitumor effect of a ruthenium(III) compound with hampered transmembrane transport, (imH)[trans-RuCl4(im)2] (KP418) in vitro and in vivo and to determine changes in metastatic potential of cells after ECT with KP418 in vitro. In addition, platinum compound cisplatin (CDDP) and ruthenium(III) compound NAMI-A were included in the experiments as reference compounds. Our results show that electroporation leads to increased cellular accumulation and cytotoxicity of KP418 in murine melanoma cell lines with low and high metastatic potential, B16-F1 and B16-F10, but not in murine fibrosarcoma cell line SA-1 in vitro which is probably due to variable effectiveness of ECT in different cell lines and tumors. Electroporation does not potentiate the cytotoxicity of KP418 as prominently as the cytotoxicity of CDDP. We also showed that the metastatic potential of cells which survived ECT with KP418 or NAMI-A does not change in vitro: resistance to detachment, invasiveness, and re-adhesion of cells after ECT is not affected. Experiments in murine tumor models B16-F1 and SA-1 showed that ECT with KP418 does not have any antitumor effect while ECT with CDDP induces significant dose-dependent tumor growth delay in the two tumor models used in vivo.

Keywords

KP418 Electrochemotherapy Ruthenium Metastatic potential In vitro In vivo 

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Rosana Hudej
    • 1
    • 2
  • Damijan Miklavcic
    • 1
  • Maja Cemazar
    • 3
    • 4
  • Vesna Todorovic
    • 3
  • Gregor Sersa
    • 3
  • Alberta Bergamo
    • 5
  • Gianni Sava
    • 5
    • 6
  • Anze Martincic
    • 7
  • Janez Scancar
    • 7
  • Bernhard K. Keppler
    • 8
  • Iztok Turel
    • 9
  1. 1.Faculty of Electrical EngineeringUniversity of LjubljanaLjubljanaSlovenia
  2. 2.BIA Separations d.o.o.AjdovscinaSlovenia
  3. 3.Institute of Oncology LjubljanaLjubljanaSlovenia
  4. 4.Faculty of Health SciencesUniversity of PrimorskaIzolaSlovenia
  5. 5.Callerio FoundationTriesteItaly
  6. 6.Department of biomedical ScienceUniversity of TriesteTriesteItaly
  7. 7.Jozef Stefan InstituteLjubljanaSlovenia
  8. 8.Institute of Inorganic ChemistryUniversity of ViennaViennaAustria
  9. 9.Faculty of Chemistry and Chemical TechnologyUniversity of LjubljanaLjubljanaSlovenia

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