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Tumor Biology

, Volume 33, Issue 4, pp 943–956 | Cite as

Cyclosporine A enables vincristine-induced apoptosis during reversal of multidrug resistance phenotype in chronic myeloid leukemia cells

  • Paloma Silva de Souza
  • Flavia da Cunha Vasconcelos
  • Luis Felipe R. Silva
  • Raquel Ciuvalschi MaiaEmail author
Research Article

Abstract

Multidrug resistance (MDR) is considered a multifactorial phenotype which prevents a successful clinical cancer treatment. This phenomenon is mainly associated with mechanisms that include drug extrusion by P-glycoprotein (Pgp) overexpression and resistance to apoptosis derived by members of the inhibitor of apoptosis proteins (IAPs), such as XIAP. Studies have proposed the use of compounds that are able to inhibit or modulate Pgp function, with no changes in the physiological expression of this protein. Based on that, the present study aimed to evaluate the reversal of MDR phenotype through modulation of Pgp efflux pump activity in leukemia multidrug-resistant cells, using a low dose of cyclosporine A (CsA). We showed that modulation of Pgp activity by using CsA did not induce cytotoxic effects in leukemia cells, independently of Pgp expression. However, during the modulation condition, we could observe that vincristine-induced apoptosis was significant in resistant cells, which was also coupled with decreasing expression of the inhibitor of apoptosis protein XIAP. In summary, our data suggest that CsA is able to reversing MDR phenotype in vitro, inducing sensibility in multidrug-resistant cells with no alterations in Pgp expression. These findings contribute to our knowledge for the circumvention of MDR in cancer cells and could be helpful for new treatment approaches.

Keywords

P-glycoprotein Cyclosporine A Vincristine MDR phenotype XIAP Chronic myeloid leukemia 

Notes

Acknowledgments

This work was supported by grants from Institutos Nacionais de Ciência e Tecnologia para Controle do Câncer, CNPq 573806/2008-0; FAPERJ EE26/170.026/2008, FAPERJ/PP-SUS, and Programa de Oncobiologia (Fundação do Câncer/UFRJ).

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2012

Authors and Affiliations

  • Paloma Silva de Souza
    • 1
    • 2
  • Flavia da Cunha Vasconcelos
    • 1
    • 2
  • Luis Felipe R. Silva
    • 1
  • Raquel Ciuvalschi Maia
    • 1
    • 3
    Email author
  1. 1.Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Pesquisa em Hemato-Oncologia Molecular, Coordenação Geral Técnico-CientíficaInstituto Nacional de Câncer (INCA)Rio de JaneiroBrazil
  2. 2.Programa de Pós Graduação Stricto Sensu em OncologiaINCARio de JaneiroBrazil
  3. 3.Serviço de Hematologia, Hospital do Câncer IINCARio de JaneiroBrazil

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