PROCHÁZKOVÁ, Jiřina, Lenka STIXOVÁ, Karel SOUČEK, Jiřina HOFMANOVÁ and Alois KOZUBÍK. Monocytic differentiation of leukemic HL-60 cells induced by co-treatment with TNF-alpha and MK886 requires activation of pro-apoptotic machinery. European Journal of Haematology. 2009, vol. 83, February, 13 pp. ISSN 0902-4441.
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Basic information
Original name Monocytic differentiation of leukemic HL-60 cells induced by co-treatment with TNF-alpha and MK886 requires activation of pro-apoptotic machinery
Authors PROCHÁZKOVÁ, Jiřina (203 Czech Republic, guarantor), Lenka STIXOVÁ (203 Czech Republic), Karel SOUČEK (203 Czech Republic), Jiřina HOFMANOVÁ (203 Czech Republic) and Alois KOZUBÍK (203 Czech Republic).
Edition European Journal of Haematology, 2009, 0902-4441.
Other information
Original language English
Type of outcome Article in a journal
Field of Study Genetics and molecular biology
Country of publisher Denmark
Confidentiality degree is not subject to a state or trade secret
Impact factor Impact factor: 2.345
RIV identification code RIV/00216224:14310/09:00028604
Organization unit Faculty of Science
UT WoS 000266875000004
Keywords in English caspases; MAPK; MK886; NFkappaB; TNF-alpha
Tags International impact, Reviewed
Changed by Changed by: Mgr. Jiřina Medalová, Ph.D., učo 176525. Changed: 25/3/2010 11:28.
Abstract
Acute myeloid leukemia cells can be cured by differentiating therapy, but it has side effects. A study of other differentiation signaling pathways is therefore useful. We demonstrated previously that the co-treatment of HL-60 cells with Tumor necrosis factor-a (TNF-a) (1 ng/mL) and inhibitor of 5-lipoxygenase MK886 (5 lM) potentiated both monocytic differentiation and apoptosis. In this study, we detected enhanced activation of three main types of MAPKs (p38, JNK, ERK). The inhibition of pro-apoptotic MAPKs (p38 and JNK) suppressed the effect of MK886 + TNF-a co-treatment. On the other hand, down-regulation of prosurvival ERK pathway led to increased differentiation. Those effects were accompanied by increased activation of caspases in cells treated by MK886 + TNF-a. 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.
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