The role of oxidative stress in 63 T-induced cytotoxicity against human lung cancer and normal lung fibroblast cell lines

Invest New Drugs. 2019 Oct;37(5):849-864. doi: 10.1007/s10637-018-0704-8. Epub 2018 Nov 29.

Abstract

It has been shown previously that molecules built on benzanilide and thiobenzanilide scaffolds possess differential biological properties including selective anticancer activity. In our previous study, we examined the cytotoxic activity and mechanism of action of the thiobenzanilide derivative N,N'-(1,2-phenylene)bis3,4,5-trifluorobenzothioamide (63 T) as a potential chemotherapeutic compound in an experimental model employing A549 lung adenocarcinoma cells and CCD39Lu non-tumorigenic lung fibroblasts. Since the results suggested oxidative stress as a co-existing mechanism of the cytotoxic effect exerted by 63 T on tested cells, studies involving the analysis of reactive oxygen species (ROS) generation and markers of oxidative stress in cells incubated with 63 T were carried out. It may be concluded that the selective activity of 63 T against cancer cells shown in our experiments is caused, at least in part, by the response of the tested cells to 63 T mediated oxidative stress in both tested cell lines.

Keywords: Antioxidative enzymes; Lung cancer; Lung fibroblast; Oxidative stress; Reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / drug therapy
  • Adenocarcinoma of Lung / metabolism
  • Adenocarcinoma of Lung / pathology*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis
  • Benzene Derivatives / pharmacology*
  • Cell Proliferation
  • Cells, Cultured
  • DNA Damage / drug effects
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibroblasts / pathology*
  • Humans
  • Lipid Peroxidation / drug effects
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology*
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Oxidative Stress / drug effects*
  • Reactive Oxygen Species / metabolism
  • Thioamides / pharmacology*

Substances

  • Antineoplastic Agents
  • Benzene Derivatives
  • N,N'-(1,2-phenylene)bis(3,4,5-trifluorobenzothioamide)
  • Reactive Oxygen Species
  • Thioamides