Esculetin modulates cytotoxicity induced by oxidants in NB4 human leukemia cells

Exp Toxicol Pathol. 2017 Oct 2;69(8):700-712. doi: 10.1016/j.etp.2017.08.001. Epub 2017 Sep 7.

Abstract

Esculetin is a polyphenolic compound with cytoprotective properties. We previously demonstrated the induction of apoptosis by esculetin in NB4 human leukemia cells, as a model, by a mechanism not well understood. To analyse the antioxidant activity of esculetin on apoptosis, we have studied the influence of co-treatments of esculetin at a concentration of 100μM with exogenous ROS donors, namely tert-butyl-hydroperoxide and hydrogen peroxide, on NB4 cells. Esculetin (100μM) exerts a protective effect on cell viability and death necrosis or late apoptosis caused by the oxidant t-BHP whereas it potentiates decrease of cell viability and cell death caused by H2O2. In the first case, the O2- scavenging activity of esculetin (100μM) could be implicated. In the last one, cytotoxicity by apoptosis induction seems to be related to the increase in O2-, among other possible mechanisms. These results contribute to the study of the antitumor properties of esculetin by regulation of redox balance in leukemia cells.

Keywords: Antioxidants; Apoptosis; Esculetin; Hydrogen peroxide; Reactive oxygen species; t-Butylhydroperoxide.

MeSH terms

  • Antioxidants / pharmacology*
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Drug Synergism
  • Humans
  • Hydrogen Peroxide / toxicity
  • Leukemia, Promyelocytic, Acute / metabolism
  • Leukemia, Promyelocytic, Acute / pathology
  • Oxidants / toxicity*
  • Oxidation-Reduction
  • Superoxides / metabolism
  • Umbelliferones / pharmacology*
  • tert-Butylhydroperoxide / toxicity

Substances

  • Antioxidants
  • Oxidants
  • Umbelliferones
  • Superoxides
  • tert-Butylhydroperoxide
  • Hydrogen Peroxide
  • esculetin