Cytotoxicity of electrophilic iron(II)-clathrochelates in human promyelocytic leukemia cell line

Bioorg Med Chem Lett. 2016 Jan 15;26(2):626-629. doi: 10.1016/j.bmcl.2015.11.060. Epub 2015 Nov 26.

Abstract

We observed that electrophilic iron(II)-clathrochelates exhibit significant cytotoxicity in human promyelocytic leukemia cells (IC50=6.5±4.6μM), which correlates with the enhancement of intracellular oxidative stress (17-fold increase with respect to the cells treated with the solvent only). Based on in vitro studies we suggested that this effect is caused by alkylation of glutathione leading to inhibition of the cellular antioxidative system and by catalytic generation of reactive oxygen species by products of the alkylation reaction.

Keywords: Alkylation; Cancer; Clathrochelate; Glutathione; Iron.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylation / drug effects
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Ferrous Compounds / chemistry*
  • Ferrous Compounds / pharmacology*
  • Glutathione / metabolism
  • Granulocyte Precursor Cells / drug effects*
  • Granulocyte Precursor Cells / metabolism
  • Granulocyte Precursor Cells / pathology
  • Humans
  • Leukemia, Promyelocytic, Acute / drug therapy*
  • Leukemia, Promyelocytic, Acute / metabolism
  • Leukemia, Promyelocytic, Acute / pathology
  • Oxidative Stress / drug effects*
  • Reactive Oxygen Species / metabolism

Substances

  • Antineoplastic Agents
  • Ferrous Compounds
  • Reactive Oxygen Species
  • Glutathione