Reversal of multidrug resistance in murine lymphoma cells by amphiphilic dihydropyridine antioxidant derivative

Marina Cindric, Ana Cipak, Julianna Serly, Aiva Plotniece, Morana Jaganjac, Lidija Mrakovcic, Tomislava Lovakovic, Azra Dedic, Ivo Soldo, Gunars Duburs, Neven Zarkovic, József Molnár

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10 Citations (Scopus)

Abstract

Background: Multidrug resistance, the principal mechanism by which cancer cells develop resistance to chemotherapy drugs, is a major factor in the failure of many forms of chemotherapies. Aim: The aim of the study was to investigate the effect of K-2-11 on the reversal of multidrug resistance. Materials and Methods: The effects of amphiphilic dihydropyridine derivative K-2-11 were tested on MDR1-expressing mouse lymphoma cells and their parental control. The effects of K-2-11 with and without doxorubicin were studied by determination of cell viability, cell proliferation and production of reactive oxygen species. Results: K-2-11 caused complete reversal of multidrug resistance of the MDR cells, being much more efficient than the positive control verapamil. Accordingly, the cytotoxic effects of doxorubicin were enhanced by K-2-11, both in the MDR and in parental cell line, while K-2-11 alone did not affect cell viability. K-2-11 also acted as an antioxidant, reducing the cellular generation of reactive oxygen species. Conclusion: Our results indicate the high potential of K-2-11 as a novel antioxidant with potent MDR-blocking ability that should be studied further for development in adjuvant anticancer treatments.

Original languageEnglish
Pages (from-to)4063-4069
Number of pages7
JournalAnticancer research
Volume30
Issue number10
Publication statusPublished - Oct 1 2010

Keywords

  • Antioxidant
  • Cancer
  • Dihydropyridine derivative
  • Doxorubicin
  • MDR reversal
  • Oxidative stress

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Cindric, M., Cipak, A., Serly, J., Plotniece, A., Jaganjac, M., Mrakovcic, L., Lovakovic, T., Dedic, A., Soldo, I., Duburs, G., Zarkovic, N., & Molnár, J. (2010). Reversal of multidrug resistance in murine lymphoma cells by amphiphilic dihydropyridine antioxidant derivative. Anticancer research, 30(10), 4063-4069.