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.
Copyright © 2011 Elsevier Ltd. All rights reserved.
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