Monocytic differentiation of leukemic HL-60 cells induced by co-treatment with TNF-alpha and MK886 requires activation of pro-apoptotic machinery

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F09%3A00028604" target="_blank" >RIV/00216224:14310/09:00028604 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68081707:_____/09:00327497

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Monocytic differentiation of leukemic HL-60 cells induced by co-treatment with TNF-alpha and MK886 requires activation of pro-apoptotic machinery

Popis výsledku v původním jazyce

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 byMK886 + 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.

Název v anglickém jazyce

Monocytic differentiation of leukemic HL-60 cells induced by co-treatment with TNF-alpha and MK886 requires activation of pro-apoptotic machinery

Popis výsledku anglicky

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 byMK886 + 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.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2009

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

European Journal of Haematology

ISSN

0902-4441

e-ISSN

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Svazek periodika

83

Číslo periodika v rámci svazku

February

Stát vydavatele periodika

DK - Dánské království

Počet stran výsledku

13

Strana od-do

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Kód UT WoS článku

000266875000004

EID výsledku v databázi Scopus

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