The effect of ATM and ERK1/2 inhibition on mitoxantrone-induced cell death of leukaemic cells

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11150%2F11%3A10104937" target="_blank" >RIV/00216208:11150/11:10104937 - isvavai.cz</a>

Výsledek na webu

<a href="http://fb.cuni.cz/file/5576/FB2011A0012.pdf" target="_blank" >http://fb.cuni.cz/file/5576/FB2011A0012.pdf</a>

DOI - Digital Object Identifier

—

Jazyk výsledku

angličtina

Název v původním jazyce

The effect of ATM and ERK1/2 inhibition on mitoxantrone-induced cell death of leukaemic cells

Popis výsledku v původním jazyce

The aim of our research was to study the effect of mitoxantrone and two protein kinase inhibitors - caffeine (inhibitor of ATM kinase) and U0126 (inhibitor of MEK1/2 kinase) on MOLT-4 and Jurkat leukaemic cell lines. In this work we show that the inhibition of MEK1/2 is associated with an increased mortality of cells after mitoxantrone (MTX) treatment. Inhibition of ATM by caffeine postponed MTX-induced cell death in MOLT-4 cells. MTX itself induced cell cycle arrest and accumulation of the cells in late S and G2/M phase. Inhibition of ATM, but not of MEK1/2, abrogated MTX-induced cell cycle arrest. Inhibition of MEK1/2 did not change MTX-induced upregulation of p53 and p21, but inhibition of ATM decreased markedly upregulation of p53 and p21 and p53 phosphorylations on serine 15 and serine 392. It can be concluded that: 1) MTX-induced phosphorylation of p53 on serine 15 and serine 392 is ATM-dependent and MEK1/2-ERK1/2 independent. 2) ATM inhibition by caffeine prevents G2 cell arrest

Název v anglickém jazyce

The effect of ATM and ERK1/2 inhibition on mitoxantrone-induced cell death of leukaemic cells

Popis výsledku anglicky

The aim of our research was to study the effect of mitoxantrone and two protein kinase inhibitors - caffeine (inhibitor of ATM kinase) and U0126 (inhibitor of MEK1/2 kinase) on MOLT-4 and Jurkat leukaemic cell lines. In this work we show that the inhibition of MEK1/2 is associated with an increased mortality of cells after mitoxantrone (MTX) treatment. Inhibition of ATM by caffeine postponed MTX-induced cell death in MOLT-4 cells. MTX itself induced cell cycle arrest and accumulation of the cells in late S and G2/M phase. Inhibition of ATM, but not of MEK1/2, abrogated MTX-induced cell cycle arrest. Inhibition of MEK1/2 did not change MTX-induced upregulation of p53 and p21, but inhibition of ATM decreased markedly upregulation of p53 and p21 and p53 phosphorylations on serine 15 and serine 392. It can be concluded that: 1) MTX-induced phosphorylation of p53 on serine 15 and serine 392 is ATM-dependent and MEK1/2-ERK1/2 independent. 2) ATM inhibition by caffeine prevents G2 cell arrest

Druh

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

CEP obor

CE - Biochemie

OECD FORD obor

—

Projekt

—

Návaznosti

Z - Vyzkumny zamer (s odkazem do CEZ)

Rok uplatnění

2011

Kód důvěrnosti údajů

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

Název periodika

Folia Biologica

ISSN

0015-5500

e-ISSN

—

Svazek periodika

57

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

CZ - Česká republika

Počet stran výsledku

8

Strana od-do

74-81

Kód UT WoS článku

000290506000005

EID výsledku v databázi Scopus

—