Pharmacological inhibition of fatty-acid oxidation synergistically enhances the effect of L-asparaginase in childhood ALL cells

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F16%3A00457034" target="_blank" >RIV/61388971:_____/16:00457034 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/67985823:_____/16:00457034 RIV/68378050:_____/16:00457034 RIV/00216208:11130/16:10323735 RIV/00216208:11310/16:10323735 RIV/00064203:_____/16:10323735

Výsledek na webu

<a href="http://dx.doi.org/10.1038/leu.2015.213" target="_blank" >http://dx.doi.org/10.1038/leu.2015.213</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/leu.2015.213" target="_blank" >10.1038/leu.2015.213</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Pharmacological inhibition of fatty-acid oxidation synergistically enhances the effect of L-asparaginase in childhood ALL cells

Popis výsledku v původním jazyce

L-asparaginase (ASNase), a key component in the treatment of childhood acute lymphoblastic leukemia (ALL), hydrolyzes plasma asparagine and glutamine and thereby disturbs metabolic homeostasis of leukemic cells. The efficacy of such therapeutic strategywill depend on the capacity of cancer cells to adapt to the metabolic challenge, which could relate to the activation of compensatory metabolic routes. Therefore, we studied the impact of ASNase on the main metabolic pathways in leukemic cells. Treatingleukemic cells with ASNase increased fatty-acid oxidation (FAO) and cell respiration and inhibited glycolysis. FAO, together with the decrease in protein translation and pyrimidine synthesis, was positively regulated through inhibition of the RagB-mTORC1pathway, whereas the effect on glycolysis was RagB-mTORC1 independent. As FAO has been suggested to have a pro-survival function in leukemic cells, we tested its contribution to cell survival following ASNase treatment. Pharmacological i

Název v anglickém jazyce

Pharmacological inhibition of fatty-acid oxidation synergistically enhances the effect of L-asparaginase in childhood ALL cells

Popis výsledku anglicky

L-asparaginase (ASNase), a key component in the treatment of childhood acute lymphoblastic leukemia (ALL), hydrolyzes plasma asparagine and glutamine and thereby disturbs metabolic homeostasis of leukemic cells. The efficacy of such therapeutic strategywill depend on the capacity of cancer cells to adapt to the metabolic challenge, which could relate to the activation of compensatory metabolic routes. Therefore, we studied the impact of ASNase on the main metabolic pathways in leukemic cells. Treatingleukemic cells with ASNase increased fatty-acid oxidation (FAO) and cell respiration and inhibited glycolysis. FAO, together with the decrease in protein translation and pyrimidine synthesis, was positively regulated through inhibition of the RagB-mTORC1pathway, whereas the effect on glycolysis was RagB-mTORC1 independent. As FAO has been suggested to have a pro-survival function in leukemic cells, we tested its contribution to cell survival following ASNase treatment. Pharmacological i

Druh

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

CEP obor

CE - Biochemie

OECD FORD obor

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Projekt

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

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

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

Název periodika

Leukemia

ISSN

0887-6924

e-ISSN

—

Svazek periodika

30

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

10

Strana od-do

209-218

Kód UT WoS článku

000369481600024

EID výsledku v databázi Scopus

2-s2.0-84953368007