Cytotoxic and Chemopreventive Effects of Gemin D Against Different Mutagens Using In Vitro and In Vivo Assays

Anticancer Agents Med Chem. 2017;17(5):712-718. doi: 10.2174/1871520616666160906092502.

Abstract

Background: Gemin D (GD) is an ellagitannin found in several plant species rich in phenolic compounds. Its many beneficial properties include antioxidant and antitumoral.

Objective: The present study assessed the genotoxicity, cytotoxicity, antigenotoxicity, and anticytotoxicity of GD by in vitro and in vivo assays.

Method: The Ames mutagenicity assay in Salmonella typhimurium, Micronucleus and Comet tests in mice were used to evaluate the biological activities mentioned above. To assess the GD's protective effects against DNA damage induced by different mutagens we performed co-, pre- and/or post-treatment in these assays.

Results: There was no genotoxic effect of GD via Ames and Micronucleus tests, but in the Comet assay the highest dose induced DNA damage. This same highest dose presented a significant cytotoxicity in mice. In the antigenotoxicity, GD protected DNA against the action of 4-nitroquinoline-1-oxide and sodium azide by Ames test, and also against the harmful action of cyclophosphamide in pre- and co-treatment by Micronucleus and Comet tests, but it did not protect DNA in post-treatment. Regarding to anticytotoxicity, GD provoked an anticytotoxic effect only during pre-treatment.

Conclusion: Therefore, GD showed relevant antigenotoxic, anticytotoxic and cytotoxic effects, which indicate that it may be a probable candidate for chemoprevention or for the development of new cancer therapies.

Keywords: Ellagitannin; ames test; comet assay; cytotoxic and protective effects against different mutagens; gemin D; micronucleus test.

MeSH terms

  • 4-Nitroquinoline-1-oxide
  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Cyclophosphamide
  • DNA Damage
  • Dose-Response Relationship, Drug
  • Hydrolyzable Tannins / chemistry
  • Hydrolyzable Tannins / pharmacology*
  • Male
  • Mice
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Mutagenicity Tests
  • Salmonella typhimurium / drug effects*
  • Salmonella typhimurium / genetics
  • Sodium Azide
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Hydrolyzable Tannins
  • gemin D
  • 4-Nitroquinoline-1-oxide
  • Cyclophosphamide
  • Sodium Azide