2009
Procházková, Jirina; Stixová, Lenka; Soucek, Karel; Hofmanová, Jirina; Kozubík, Alois
In: European journal of haematology, vol. 83, no. 1, pp. 35–47, 2009, ISSN: 1600-0609 0902-4441, (Place: England).
Abstract | Links | BibTeX | Tags: Acute/*drug therapy/metabolism/*pathology, Amino Acid Chloromethyl Ketones/pharmacology, Apoptosis/*drug effects/physiology, Caspase Inhibitors, Caspases/metabolism, Cell Differentiation/drug effects, Cysteine Proteinase Inhibitors/pharmacology, Enzyme Activation/drug effects, HL-60 Cells, Humans, Indoles/*pharmacology, Leukemia, Lipoxygenase Inhibitors/pharmacology, MAP Kinase Signaling System/drug effects, Monocytes/*drug effects/pathology, NF-kappa B/antagonists & inhibitors, Promyelocytic, Tumor Necrosis Factor-alpha/*pharmacology
@article{prochazkova_monocytic_2009,
title = {Monocytic differentiation of leukemic HL-60 cells induced by co-treatment with TNF-alpha and MK886 requires activation of pro-apoptotic machinery.},
author = {Jirina Procházková and Lenka Stixová and Karel Soucek and Jirina Hofmanová and Alois Kozubík},
doi = {10.1111/j.1600-0609.2009.01240.x},
issn = {1600-0609 0902-4441},
year = {2009},
date = {2009-07-01},
journal = {European journal of haematology},
volume = {83},
number = {1},
pages = {35–47},
abstract = {The block of hematopoietic differentiation program in acute myeloid leukemia cells can be overcome by differentiating agent like retinoic acid, but it has several side effects. A study of other differentiation signaling pathways is therefore useful to predict potential targets of anti-leukemic therapy. We demonstrated previously that the co-treatment of HL-60 cells with Tumor necrosis factor-alpha (TNF-alpha) (1 ng/mL) and inhibitor of 5-lipoxygenase MK886 (5 microm) potentiated both monocytic differentiation and apoptosis. In this study, we detected enhanced activation of three main types of mitogen-activated protein kinases (MAPKs) (p38, c-Jun amino-terminal kinase [JNK], extracellular signal-regulated kinase [ERK]), so we assessed their role in differentiation using appropriate pharmacologic inhibitors. The inhibition of pro-apoptotic MAPKs (p38 and JNK) suppressed the effect of MK886 + TNF-alpha co-treatment. On the other hand, down-regulation of pro-survival ERK pathway led to increased differentiation. Those effects were accompanied by increased activation of caspases in cells treated by MK886 + TNF-alpha. Pan-caspase inhibitor ZVAD-fmk significantly decreased both number of apoptotic and differentiated cells. The same effect was observed after inhibition of caspase 9, but not caspase 3 and 8. To conclude, we evidenced that the activation of apoptotic processes and pathways supporting apoptosis (p38 and JNK MAPKs) is required for the monocytic differentiation of HL-60 cells.},
note = {Place: England},
keywords = {Acute/*drug therapy/metabolism/*pathology, Amino Acid Chloromethyl Ketones/pharmacology, Apoptosis/*drug effects/physiology, Caspase Inhibitors, Caspases/metabolism, Cell Differentiation/drug effects, Cysteine Proteinase Inhibitors/pharmacology, Enzyme Activation/drug effects, HL-60 Cells, Humans, Indoles/*pharmacology, Leukemia, Lipoxygenase Inhibitors/pharmacology, MAP Kinase Signaling System/drug effects, Monocytes/*drug effects/pathology, NF-kappa B/antagonists & inhibitors, Promyelocytic, Tumor Necrosis Factor-alpha/*pharmacology},
pubstate = {published},
tppubtype = {article}
}
The block of hematopoietic differentiation program in acute myeloid leukemia cells can be overcome by differentiating agent like retinoic acid, but it has several side effects. A study of other differentiation signaling pathways is therefore useful to predict potential targets of anti-leukemic therapy. We demonstrated previously that the co-treatment of HL-60 cells with Tumor necrosis factor-alpha (TNF-alpha) (1 ng/mL) and inhibitor of 5-lipoxygenase MK886 (5 microm) potentiated both monocytic differentiation and apoptosis. In this study, we detected enhanced activation of three main types of mitogen-activated protein kinases (MAPKs) (p38, c-Jun amino-terminal kinase [JNK], extracellular signal-regulated kinase [ERK]), so we assessed their role in differentiation using appropriate pharmacologic inhibitors. The inhibition of pro-apoptotic MAPKs (p38 and JNK) suppressed the effect of MK886 + TNF-alpha co-treatment. On the other hand, down-regulation of pro-survival ERK pathway led to increased differentiation. Those effects were accompanied by increased activation of caspases in cells treated by MK886 + TNF-alpha. Pan-caspase inhibitor ZVAD-fmk significantly decreased both number of apoptotic and differentiated cells. The same effect was observed after inhibition of caspase 9, but not caspase 3 and 8. To conclude, we evidenced that the activation of apoptotic processes and pathways supporting apoptosis (p38 and JNK MAPKs) is required for the monocytic differentiation of HL-60 cells.