Genotoxic and cytotoxic effects produced by acetogenins obtained from Annona cherimolia Mill

Biol Pharm Bull. 2008 Dec;31(12):2346-9. doi: 10.1248/bpb.31.2346.

Abstract

In the present study we extracted three isomeric acetogenins (Ace) from the seeds of Annona cherimolia Mill. (Annonaceae) and determined their genotoxic and cytotoxic potential in mice. Our results showed a significant increase in the rate of micronucleated polychromatic erythrocytes induced by Ace with respect to the value for the control group; the effect was less pronounced than that observed with daunorubicin (Dau). To evaluate cytotoxicity, we determined the proportion of polychromatic erythrocytes with respect to the number of normochromatic erythrocytes, and we found an inhibitory effect induced by Ace that was quite similar to that observed with Dau. Besides, by means of the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide test, we also determined the cytotoxicity of Ace in both a normal fibroblast mouse cell line and in a line derived from human colon cancer. In this assay, the strongest decrease in viability corresponded to the malignant cell line. Our results established for the first time the genotoxic capacity of these compounds in vivo, and confirmed their cytotoxic potential in cultured cells.

MeSH terms

  • Acetogenins / chemistry*
  • Acetogenins / toxicity*
  • Animals
  • Annona / chemistry*
  • Antineoplastic Agents, Phytogenic / toxicity*
  • Bone Marrow Cells / drug effects
  • Cell Survival / drug effects
  • Drug Screening Assays, Antitumor
  • Erythrocytes / drug effects
  • Erythrocytes / ultrastructure
  • Humans
  • In Vitro Techniques
  • Isomerism
  • Lethal Dose 50
  • Mice
  • Micronucleus Tests
  • Mutagens / toxicity*
  • Seeds / chemistry
  • Tetrazolium Salts
  • Thiazoles

Substances

  • Acetogenins
  • Antineoplastic Agents, Phytogenic
  • Mutagens
  • Tetrazolium Salts
  • Thiazoles
  • thiazolyl blue