Dequalinium induces human leukemia cell death by affecting the redox balance

Leuk Res. 2011 Oct;35(10):1395-401. doi: 10.1016/j.leukres.2011.03.012. Epub 2011 Apr 8.

Abstract

Dequalinium, an amphiphilic quinolinium derivative, selectively accumulates in mitochondria and displays anticancer activity in cells from different malignancies. Previous studies indicate a differential DQA-induced cytotoxicity in NB4 and K562 human leukemia cells as a consequence of an early disturbance in mitochondrial function. Results in this paper show that DQA induces a concentration-dependent oxidative stress by decreasing GSH level and increasing ROS in a cell type specific way. Inhibitors of the JNK and p38 stress regulated kinases potentiate DQA-induced NB4 cell death suggesting a protective function for these enzymes. K562 cells with relatively high GSH levels remained resistant to DQA action.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Blotting, Western
  • Cell Line, Tumor
  • Dequalinium* / pharmacology
  • Drug Synergism
  • Glutathione / analysis
  • Glutathione / biosynthesis
  • Humans
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Leukemia / drug therapy*
  • Leukemia / enzymology
  • Leukemia / pathology
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Organ Specificity
  • Oxidation-Reduction / drug effects
  • Oxidative Stress / drug effects
  • Protein Kinase Inhibitors / pharmacology
  • Reactive Oxygen Species / metabolism
  • Superoxides / analysis
  • Surface-Active Agents / pharmacology
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Protein Kinase Inhibitors
  • Reactive Oxygen Species
  • Surface-Active Agents
  • Superoxides
  • Dequalinium
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Glutathione