Dequalinium induces human leukemia cell death by affecting the redox balance.

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.

• Authors: Ana I García-Pérez, Eva Galeano, Elena Nieto, Pilar Sancho
• Journal: Leukemia research (Leuk Res) Vol. 35 Issue 10 Pg. 1395-401 (Oct 2011) ISSN: 1873-5835 [Electronic] England
• PMID: 21477862 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

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

Topics

• Apoptosis (drug effects)
• Blotting, Western
• Cell Line, Tumor
• Dequalinium (pharmacology)
• Drug Synergism
• Glutathione (analysis, biosynthesis)
• Humans
• JNK Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)
• Leukemia (drug therapy, enzymology, pathology)
• Mitochondria (drug effects, 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, metabolism)