title: 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.affiliation: Departamento de Bioquímica y Biología Molecular, Universidad de Alcalá, Alcala de Henares, Madrid, Spain. ana.garcia@uah.es
authors.forename: Ana I
authors.initials: AI
authors.lastname: García-Pérez
authors.forename: Eva
authors.initials: E
authors.lastname: Galeano
authors.forename: Elena
authors.initials: E
authors.lastname: Nieto
authors.forename: Pilar
authors.initials: P
authors.lastname: Sancho
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003868:Dequalinium / Q000494:pharmacology; D004357:Drug Synergism; D005978:Glutathione / Q000032:analysis / Q000096:biosynthesis; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D007938:Leukemia / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009928:Organ Specificity; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000032:analysis; D013501:Surface-Active Agents / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; D013501:Surface-Active Agents; D013481:Superoxides; D003868:Dequalinium; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D005978:Glutathione