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

Júlia Teixeira de Oliveira1,2, Maria C da Silva Barbosa1,2, Luiz F de Camargos1,2

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

Cytotechnology
|March 22, 2017
PubMed

Insights

Digoxin exhibits anticancer potential but can be cytotoxic, genotoxic, and mutagenic at high doses. However, at therapeutic concentrations, it shows a protective effect against the mutagen Mitomycin C (MMC).

Area of Science:

  • Pharmacology
  • Toxicology
  • Oncology

Background:

  • Digoxin is a widely used heart failure medication with demonstrated anticancer properties.
  • Digoxin's potential to interact with other medical compounds necessitates further investigation.
  • Understanding digoxin's toxicological profile is crucial given its dual role.

Purpose of the Study:

  • To evaluate the in vitro cytotoxicity, genotoxicity, and mutagenicity of digoxin.
  • To assess digoxin's potential to interact with Mitomycin C (MMC).
  • To explore digoxin's chemoprotective effects in the context of chemotherapy.

Main Methods:

  • Cytotoxicity assessed via MTT assay.
  • Genotoxicity evaluated using the comet assay in CHO-K1 and HeLa cells.
  • Mutagenicity and antimutagenicity determined by cytokinesis-block micronucleus assay and Ames test (S. typhimurium TA98, TA100).

Main Results:

  • Digoxin demonstrated cytotoxicity, genotoxicity, and mutagenicity in HeLa and CHO-K1 cells at supra-therapeutic concentrations.
  • An antimutagenic effect of digoxin against Mitomycin C (MMC) was observed at therapeutically relevant concentrations.
  • Digoxin showed a chemoprotective effect against MMC-induced mutagenicity in both cell lines.

Conclusions:

  • Digoxin exhibits a dual effect: cytotoxic/genotoxic/mutagenic at high doses, but antimutagenic at therapeutic doses.
  • The observed chemoprotective effect of digoxin against MMC warrants further research for anticancer chemotherapy applications.
  • Digoxin's interactions and effects at therapeutic levels may offer novel strategies in cancer treatment.
Keywords:
AntimutagenicityDesmutagenGenotoxicityMutagenicity

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