, Volume 27, Issue 3, pp 459–469 | Cite as

The ruthenium complexes cis-(dichloro)tetramineruthenium(III) chloride and cis-tetraammine(oxalato)ruthenium(III) dithionate overcome resistance inducing apoptosis on human lung carcinoma cells (A549)

  • Cesar Augusto Sam Tiago Vilanova-Costa
  • Hellen Karine Paes Porto
  • Flávia de Castro Pereira
  • Aliny Pereira de Lima
  • Wagner Batista dos Santos
  • Elisângela de Paula Silveira-LacerdaEmail author


Lung cancer is one of the leading causes of death in the world, and non-small cell lung carcinoma accounts for approximately 75–85 % of all lung cancers. In the present work, we studied the antitumor activity of the compound cis-(dichloro)tetramineruthenium(III) chloride {cis-[RuCl2(NH3)4]Cl} against human lung carcinoma tumor cell line A549. The present study aimed to investigate the relationship between the expression of MDR1 and CYP450 genes in human lung carcinoma cell lines A549 treated with cisCarboPt, cisCRu(III) and cisDRu(III). The ruthenium-based coordinated complexes presented low cytotoxic and antiproliferative activities, with high IC50 values, 196 (±15.49), 472 (±20.29) and 175 (±1.41) for cisCarboPt, cisCRu(III) and cisDRu(III), respectively. The tested compounds induced apoptosis in A549 tumor cells as evidenced by caspase 3 activation, but only at high concentrations. Results also revealed that the amplification of P-gp gene is greater in A549 cells exposed to cisCarboPt and cisCRu(III) than cisDRu(III). Taken together all these results strongly demonstrate that MDR-1 over-expression in A549 cells could be associated to a MDR phenotype of these cells and moreover, it is also contributing to the platinum, and structurally-related compound, resistance in these cells. The identification and characterization of novel mechanisms of drug resistance will enable the development of a new generation of anti-cancer drugs that increase cancer sensitivity and/or represent more effective chemotherapeutic agents.


Carboplatin cis-(Dichloro)tetrammineruthenium(III) chloride cis-Tetraammine(oxalato)ruthenium(III) dithionate A549 MDR-1 CYPs 



The authors gratefully acknowledge the financial support of Research and Projects Financing (FINEP) (Grant No.01.06.0941.00/CT-Saúde to Elisângela de Paula Silveira-Lacerda) and Foundation for the Support of Research in the State of Goias (FAPEG). Coordination for the Advancement of Higher Education Staff (CAPES) through fellowship to Cesar Augusto Sam Tiago Vilanova-Costa, Flávia de Castro Pereira and Hellen Karine Paes Porto; and Brazilian National Council of Technological and Scientific Development (CNPq) through fellowship to Aliny Pereira de Lima (Grant No. 141648/2010-4). There are no financial or personal interests that might be viewed as inappropriate influences on the work presented herein. This manuscript was completely financed by governmental and nonprofit institutions, the Brazilian National Counsel of Technological and Scientific Development (CNPq), Research and Projects Financing (FINEP), Coordination for the Advancement of Higher Education Staff (CAPES) and Foundation for the Support of Research in the State of Goias (FAPEG).

Ethical Approval

No studies involving humans or experimental animals were conducted in this work. The human lung carcinoma A549 cells were purchased from the American Type Culture Collection (ATCC, Rockville, MD, USA) and cultured in vitro.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Cesar Augusto Sam Tiago Vilanova-Costa
    • 1
  • Hellen Karine Paes Porto
    • 1
  • Flávia de Castro Pereira
    • 1
  • Aliny Pereira de Lima
    • 1
  • Wagner Batista dos Santos
    • 2
  • Elisângela de Paula Silveira-Lacerda
    • 1
    Email author
  1. 1.Laboratório de Genética Molecular e Citogenética, Instituto de Ciências BiológicasUniversidade Federal de Goiás - UFGGoiâniaBrazil
  2. 2.Instituto de Ciências Exatas e da TerraUniversidade Federal de Mato Grosso - UFMTBarra do GarçasBrazil

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