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.
2006
Stika, Jirí; Vondrácek, Jan; Hofmanová, Jirina; Simek, Vladimír; Kozubík, Alois
MK-886 enhances tumour necrosis factor-alpha-induced differentiation and apoptosis. Journal Article
In: Cancer letters, vol. 237, no. 2, pp. 263–271, 2006, ISSN: 0304-3835, (Place: Ireland).
Abstract | Links | BibTeX | Tags: *Apoptosis, Arachidonate 5-Lipoxygenase/metabolism, Cell Cycle, Cell Differentiation, Cell Line, Cell Survival, HL-60 Cells, Humans, Indoles/*pharmacology, Lipoxygenase Inhibitors/*pharmacology, Signal Transduction, Time Factors, Tumor, Tumor Necrosis Factor-alpha/*metabolism
@article{stika_mk-886_2006,
title = {MK-886 enhances tumour necrosis factor-alpha-induced differentiation and apoptosis.},
author = {Jirí Stika and Jan Vondrácek and Jirina Hofmanová and Vladimír Simek and Alois Kozubík},
doi = {10.1016/j.canlet.2005.06.012},
issn = {0304-3835},
year = {2006},
date = {2006-06-01},
journal = {Cancer letters},
volume = {237},
number = {2},
pages = {263–271},
abstract = {We investigated the role of the 5-lipoxygenase (5-LOX) pathway of arachidonic acid metabolism in tumour necrosis factor-alpha (TNF-alpha)-induced differentiation of human leukemic HL-60 cells using MK-886, an inhibitor of 5-LOX activating protein. MK-886 augmented cell cycle arrest and differentiation induced by TNF-alpha; however, both effects were probably 5-LOX-independent, because a general LOX inhibitor, NDGA, had no effect. Apoptosis was significantly elevated after combined TNF-alpha and MK-886 treatment, which could be partially associated with changes of Mcl-1 protein expression. NF-kappaB signalling or activation of JNKs were not modulated by MK-886. Thus, in addition to apoptosis, MK-886 can enhance TNF-alpha-induced differentiation.},
note = {Place: Ireland},
keywords = {*Apoptosis, Arachidonate 5-Lipoxygenase/metabolism, Cell Cycle, Cell Differentiation, Cell Line, Cell Survival, HL-60 Cells, Humans, Indoles/*pharmacology, Lipoxygenase Inhibitors/*pharmacology, Signal Transduction, Time Factors, Tumor, Tumor Necrosis Factor-alpha/*metabolism},
pubstate = {published},
tppubtype = {article}
}
We investigated the role of the 5-lipoxygenase (5-LOX) pathway of arachidonic acid metabolism in tumour necrosis factor-alpha (TNF-alpha)-induced differentiation of human leukemic HL-60 cells using MK-886, an inhibitor of 5-LOX activating protein. MK-886 augmented cell cycle arrest and differentiation induced by TNF-alpha; however, both effects were probably 5-LOX-independent, because a general LOX inhibitor, NDGA, had no effect. Apoptosis was significantly elevated after combined TNF-alpha and MK-886 treatment, which could be partially associated with changes of Mcl-1 protein expression. NF-kappaB signalling or activation of JNKs were not modulated by MK-886. Thus, in addition to apoptosis, MK-886 can enhance TNF-alpha-induced differentiation.