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Digoxin reduces the mutagenic effects of Mitomycin C in human and rodent cell lines

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Abstract

Digoxin is a drug widely used to treat heart failure and studies have demonstrated its potential as anticancer agent. In addition, digoxin presents the potential to interact with a series of other compounds used in medicine. The aim of the present study was to evaluate in vitro the cytotoxicity, genotoxicity and mutagenicity of digoxin and its potential to interact with the mutagen Mitomycin C (MMC). The cytotoxicity of digoxin was assessed by employing the MTT method and the comet assay was performed to assess the genotoxicity of this medicine in CHO-K1 and HeLa cell lines. Besides, the cytokinesis-block micronucleus assay was performed to assess the mutagenicity and the antimutagenicity of this drug. The Ames assay was also performed with TA98 and TA100 strains of S. typhimurium. Results showed that digoxin was cytotoxic, genotoxic and mutagenic for HeLa and CHO-K1 cell lines at concentrations many times higher than those observed in human therapeutic conditions. Nevertheless, an antimutagenic effect against the mutagen MMC was observed on both cell lines in concentrations near those used therapeutically in humans. This chemoprotective effect observed is an interesting finding that should be better explored regarding its impact in anticancer chemotherapy.

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Acknowledgements

The authors would like to acknowledge the financial support from the Fundação de Amparo à Pesquisa de Minas Gerais—FAPEMIG (APQ-01254-15; CBB-PPM-00560-13), and the Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq (478629/2013-3).

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Authors and Affiliations

  1. Laboratório de Biologia Celular e Mutagênese (LaBCeM), Universidade Federal de São João del Rei (UFSJ), Divinópolis, MG, 35501-506, Brazil

    Júlia Teixeira de Oliveira, Maria C. da Silva Barbosa, Luiz F. de Camargos, Isabella Viana Gomes da Silva, Vanessa J. da Silva Vieira dos Santos & Fabio Vieira dos Santos

  2. Núcleo de Pesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei (UFSJ), Divinópolis, MG, 35501-296, Brazil

    Júlia Teixeira de Oliveira, Maria C. da Silva Barbosa, Luiz F. de Camargos, Fernando de Pilla Varotti & Fabio Vieira dos Santos

  3. Serviço de Biologia Celular (SBC), Fundação Ezequiel Dias (FUNED), Belo Horizonte, MG, 30510-010, Brazil

    Luciana M. da Silva

  4. Departamento de Zootecnia (DZOO), Universidade Federal de São João del Rei (UFSJ), São João del Rei, MG, 36301-160, Brazil

    Leonardo Marmo Moreira

  5. Departamento de Ciências Naturais (DCNAT), Universidade Federal de São João del Rei (UFSJ), São João del Rei, MG, 36301-160, Brazil

    Juliana Pereira Lyon

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  1. Júlia Teixeira de Oliveira
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  2. Maria C. da Silva Barbosa
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  3. Luiz F. de Camargos
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  4. Isabella Viana Gomes da Silva
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Correspondence to Fabio Vieira dos Santos.

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de Oliveira, J.T., Barbosa, M.C.d., de Camargos, L.F. et al. Digoxin reduces the mutagenic effects of Mitomycin C in human and rodent cell lines. Cytotechnology 69, 699–710 (2017). https://doi.org/10.1007/s10616-017-0078-3

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