Dequalinium induces cytotoxicity in human leukemia NB4 cells by downregulation of Raf/MEK/ERK and PI3K/Akt signaling pathways and potentiation of specific inhibitors of these pathways.

Abstract	Delocalized lipophilic cation dequalinium (DQA) selectively accumulates in mitochondria and displays anticancer activity in different malignancies. Our previous studies indicate a DQA-induced cytotoxicity in human acute promyelocytic leukemia NB4 cells by early disturbance in mitochondrial function and oxidative stress. This study shows the ability of DQA to downregulate Raf/MEK/ERK1/2 and PI3K/Akt signaling pathways in NB4 cells which leads to cell death by apoptosis and/or necrosis. Moreover, DQA potentiates the action of specific inhibitors of these pathways. These DQA effects could be mediated by redox regulation of Akt. Our results contribute to a better understanding of the cytotoxic DQA mechanism on leukemia cells and encourage the performance of further studies in combination with other agents such as kinase inhibitors for improving the efficacy of therapies against acute promyelocytic leukemia.
Authors	Ana I García-Pérez, Eva Galeano, Elena Nieto, M Cristina Estañ, Pilar Sancho
Journal	Leukemia research (Leuk Res) Vol. 38 Issue 7 Pg. 795-803 (Jul 2014) ISSN: 1873-5835 [Electronic] England
PMID	24811390 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright	Copyright © 2014 Elsevier Ltd. All rights reserved.
Chemical References	Phosphoinositide-3 Kinase Inhibitors Dequalinium Proto-Oncogene Proteins c-akt raf Kinases Extracellular Signal-Regulated MAP Kinases Mitogen-Activated Protein Kinase Kinases Glutathione
Topics	Apoptosis (drug effects) Dequalinium (pharmacology) Down-Regulation Extracellular Signal-Regulated MAP Kinases (antagonists & inhibitors, physiology) Glutathione (metabolism) Humans Leukemia (drug therapy, pathology) Mitogen-Activated Protein Kinase Kinases (antagonists & inhibitors, physiology) Phosphatidylinositol 3-Kinases (physiology) Phosphoinositide-3 Kinase Inhibitors Proto-Oncogene Proteins c-akt (antagonists & inhibitors, physiology) Signal Transduction (drug effects) raf Kinases (antagonists & inhibitors, physiology)

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