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. 2017 Aug;69(4):699-710.
doi: 10.1007/s10616-017-0078-3. Epub 2017 Mar 20.

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

Júlia Teixeira de Oliveira  1   2 , Maria C da Silva Barbosa  1   2 , Luiz F de Camargos  1   2 , Isabella Viana Gomes da Silva  1 , Fernando de Pilla Varotti  2 , Luciana M da Silva  3 , Leonardo Marmo Moreira  4 , Juliana Pereira Lyon  5 , Vanessa J da Silva Vieira Dos Santos  1 , Fabio Vieira Dos Santos  6   7
Affiliations

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

Júlia Teixeira de Oliveira et al. Cytotechnology. 2017 Aug.

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.

Keywords: Antimutagenicity; Desmutagen; Genotoxicity; Mutagenicity.

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Conflict of interest statement

The authors declare that there are no conflicts of interest.

Figures

Fig. 1
Fig. 1
Schema of treatments in CBMN assay for evaluation of the antimutagenicity in HeLa and CHO-K1 cell lines
Fig. 2
Fig. 2
Cell viability obtained from the MTT assay performed with the CHO-K1 cell line after treatment with different concentrations of digoxin in 24–48 h of exposition. *(p < 0.05)
Fig. 3
Fig. 3
Mean of the scores and standard deviation obtained in Alkaline Comet assay performed with different concentrations of digoxin in CHO-K1 and HeLa cell lines. MMS: methyl methanesulfonate (120 µM); *statistically different (p < 0.05) from negative control (PBS)
Fig. 4
Fig. 4
Mean of the frequency of revertants per plate and standard deviation in Ames assay performed with the strains TA98 and TA100 of Salmonella typhimurium to assess different concentrations of digoxin, with (+S9) or without (−S9) metabolic activation
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