Traumatic acid toxicity mechanisms in human breast cancer MCF-7 cells

Regul Toxicol Pharmacol. 2019 Aug:106:137-146. doi: 10.1016/j.yrtph.2019.04.023. Epub 2019 May 2.

Abstract

Traumatic acid (TA) - an oxidative derivative of unsaturated fatty acids, belongs to the cytokinins category - a group of plant hormones, which play an important role in growth and development. Previously we demonstrated its positive influence on oxidative stress parameters in normal human fibroblasts, therefore we decided to investigate its activity in cancer cells. MCF-7 breast cancer cell line was chosen as an experimental model because of proved association between the consumption of dietary fat and the incidence of breast cancer. TA cytotoxicity and its effects on MCF-7 cells proliferation, viability, apoptosis/necrosis, thiol group content, lipid peroxidation, reduced/oxidized glutathione (GSH/GSSG) and ROS (reactive oxygen species) content was examined. The results show a significant effect of TA on tested parameters. TA caused a decrease in cells proliferation and viability, GSH/GSSG ratio and thiol group content. It increases caspase 7 activity, membrane lipid peroxidation and ROS content, simultaneously reducing breast cancer cell growth through oxidative stress influence on apoptosis. The present findings reveal that TA exhibits multiple and complex activity in MCF-7 breast cancer cells and it exhibits potential anticancer properties and tumor preventive activity.

Keywords: Apoptosis; Glutathione; MCF-7; Oxidative stress; Reactive oxygen species; Traumatic acid.

MeSH terms

  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dicarboxylic Acids / adverse effects
  • Dicarboxylic Acids / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • Lipid Peroxidation / drug effects
  • MCF-7 Cells
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Dicarboxylic Acids
  • traumatic acid