PMID- 19220423
OWN - NLM
STAT- MEDLINE
DCOM- 20090702
LR  - 20161125
IS  - 1600-0609 (Electronic)
IS  - 0902-4441 (Linking)
VI  - 83
IP  - 1
DP  - 2009 Jul
TI  - Monocytic differentiation of leukemic HL-60 cells induced by co-treatment with 
      TNF-alpha and MK886 requires activation of pro-apoptotic machinery.
PG  - 35-47
LID - 10.1111/j.1600-0609.2009.01240.x [doi]
AB  - 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.
FAU - Prochazkova, Jirina
AU  - Prochazkova J
AD  - Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of Czech 
      Republic, vvi, Brno, Czech Republic.
FAU - Stixova, Lenka
AU  - Stixova L
FAU - Soucek, Karel
AU  - Soucek K
FAU - Hofmanova, Jirina
AU  - Hofmanova J
FAU - Kozubik, Alois
AU  - Kozubik A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090205
PL  - England
TA  - Eur J Haematol
JT  - European journal of haematology
JID - 8703985
RN  - 0 (Amino Acid Chloromethyl Ketones)
RN  - 0 (Caspase Inhibitors)
RN  - 0 (Cysteine Proteinase Inhibitors)
RN  - 0 (Indoles)
RN  - 0 (Lipoxygenase Inhibitors)
RN  - 0 (NF-kappa B)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone)
RN  - 080626SQ8C (MK-886)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Amino Acid Chloromethyl Ketones/pharmacology
MH  - Apoptosis/*drug effects/physiology
MH  - Caspase Inhibitors
MH  - Caspases/metabolism
MH  - Cell Differentiation/drug effects
MH  - Cysteine Proteinase Inhibitors/pharmacology
MH  - Enzyme Activation/drug effects
MH  - HL-60 Cells
MH  - Humans
MH  - Indoles/*pharmacology
MH  - Leukemia, Promyelocytic, Acute/*drug therapy/metabolism/*pathology
MH  - Lipoxygenase Inhibitors/pharmacology
MH  - MAP Kinase Signaling System/drug effects
MH  - Monocytes/*drug effects/pathology
MH  - NF-kappa B/antagonists & inhibitors
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 2009/02/18 09:00
MHDA- 2009/07/03 09:00
CRDT- 2009/02/18 09:00
PHST- 2009/02/18 09:00 [entrez]
PHST- 2009/02/18 09:00 [pubmed]
PHST- 2009/07/03 09:00 [medline]
AID - EJH1240 [pii]
AID - 10.1111/j.1600-0609.2009.01240.x [doi]
PST - ppublish
SO  - Eur J Haematol. 2009 Jul;83(1):35-47. doi: 10.1111/j.1600-0609.2009.01240.x. Epub 
      2009 Feb 5.