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Induction of Cell Cycle Arrest and Apoptosis by Ruthenium Complex cis-(Dichloro)tetramineruthenium(III) Chloride in Human Lung Carcinoma Cells A549

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Abstract

Lung cancer is one of the leading causes of death in the world, and non-small cell lung carcinoma (NSCLC) accounts for approximately 75–85% of all lung cancers. In the present work, we studied the cytotoxic activity, cell cycle arrest and induction apoptosis of the compound cis-(dichloro)tetramineruthenium(III) chloride {cis-[RuCl2(NH3)4]Cl} in human lung carcinoma tumor cell line A549. The results of MTT and trypan blue assays showed that cis-[RuCl2(NH3)4]Cl causes reduction in the viability of A549 cells when treating with 95 and 383 μM of the compound for 48 and 72 h. Lower concentrations of the compound (19, 3.8 and 0.38 μM), however, only slightly affected cell viability. The IC50 value for the compound was about 383 μM. Survival analysis of the A549 cells after treatment with ruthenium(III) compound using long term clonogenic assay showed that it reduced colony formation ability at concentrations of 0.38 and 3.8 μM, and at concentrations of 95 and 383 μM no colonies were observed. Cell cycle analysis showed that compound ruthenium led to an accumulation of A549 cells in S phase and increased in the sub-G1 peak. In addition, cis-(dichloro)tetramineruthenium(III) chloride treatment induced apoptosis, as observed by the increased numbers of annexin V-positive cells and increased messenger RNA expression of caspase-3.

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Acknowledgments

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). Support from Coordination for the Advancement of Higher Education Staff (CAPES) was provided through a fellowship to Aliny Pereira de Lima and Cesar Augusto Sam Tiago Vilanova-Costa, and from the Brazilian National Counsel of Technological and Scientific Development (CNPq) through a fellowship to Flávia de Castro Pereira (grant No. 131960/2008-3).

Conflict of Interest

There are no financial or personal interests that might be viewed as inappropriate influences on the work presented herein.

Ethical Approval

No studies involving humans or experimental animals were conducted in this work. The human lung carcinoma A549 cells were purchased from the Rio de Janeiro Cell Bank (RJ, Brazil) and cultured in vitro.

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Authors and Affiliations

  1. Laboratório de Genética Molecular e Citogenética, Instituto de Ciências Biológicas- ICB I - Sala 200 - UFG, Campus Samambaia (Campus II)., Universidade Federal de Goiás—UFG., Goiânia, Goiás, Brazil

    Aliny Pereira de Lima, Flávia de Castro Pereira, Cesar Augusto Sam Tiago Vilanova-Costa, Jordana Ribeiro Soares, Lucas Carlos Gomes Pereira, Hellen Karine Paes Porto & Elisângela de Paula Silveira-Lacerda

  2. Instituto de Química, Universidade Federal de Uberlândia—UFU., Uberlândia, Minas Gerais, Brazil

    Luiz Alfredo Pavanin

  3. Instituto de Química, Universidade Federal de Mato Grosso—UFMT., Barra do Garça, Mato Grosso, Brazil

    Wagner Batista dos Santos

Authors
  1. Aliny Pereira de Lima
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  2. Flávia de Castro Pereira
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  3. Cesar Augusto Sam Tiago Vilanova-Costa
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  4. Jordana Ribeiro Soares
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  5. Lucas Carlos Gomes Pereira
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  6. Hellen Karine Paes Porto
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  7. Luiz Alfredo Pavanin
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  8. Wagner Batista dos Santos
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  9. Elisângela de Paula Silveira-Lacerda
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Correspondence to Elisângela de Paula Silveira-Lacerda.

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de Lima, A.P., Pereira, F.d.C., Vilanova-Costa, C.A.S.T. et al. Induction of Cell Cycle Arrest and Apoptosis by Ruthenium Complex cis-(Dichloro)tetramineruthenium(III) Chloride in Human Lung Carcinoma Cells A549. Biol Trace Elem Res 147, 8–15 (2012). https://doi.org/10.1007/s12011-011-9275-7

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  • DOI: https://doi.org/10.1007/s12011-011-9275-7

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