Počet záznamů: 1
Pharmacological inhibition of fatty-acid oxidation synergistically enhances the effect of L-asparaginase in childhood ALL cells
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SYSNO ASEP 0457034 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Pharmacological inhibition of fatty-acid oxidation synergistically enhances the effect of L-asparaginase in childhood ALL cells Tvůrce(i) Heřmanová, I. (CZ)
Arruabarrena-Aristorena, A. (ES)
Vališ, Karel (MBU-M) ORCID
Nůsková, Hana (FGU-C) RID, ORCID
Alberich-Jorda, Meritxell (UMG-J) RID
Fišer, K. (CZ)
Fernandez-Ruiz, S. (ES)
Kavan, Daniel (MBU-M) RID, ORCID
Pecinová, Alena (FGU-C) RID, ORCID, SAI
Niso-Santano, N. (FR)
Žaliová, M. (CZ)
Novák, Petr (MBU-M) RID, ORCID
Houštěk, Josef (FGU-C) RID, ORCID
Mráček, Tomáš (FGU-C) RID, ORCID
Kroemer, G. (FR)
Carracedo, A. (ES)
Trka, J. (CZ)
Starková, J. (CZ)Zdroj.dok. Leukemia. - : Springer - ISSN 0887-6924
Roč. 30, č. 1 (2016), s. 209-218Poč.str. 10 s. Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova ACUTE LYMPHOBLASTIC-LEUKEMIA ; ACUTE MYELOID-LEUKEMIA ; OVARIAN-CANCER Vědní obor RIV CE - Biochemie Vědní obor RIV – spolupráce Ústav molekulární genetiky - Genetika a molekulární biologie
Fyziologický ústav - Genetika a molekulární biologieCEP GBP302/12/G101 GA ČR - Grantová agentura ČR NV15-28848A GA MZd - Ministerstvo zdravotnictví LK21307 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy GB14-36804G GA ČR - Grantová agentura ČR NT12370 GA MZd - Ministerstvo zdravotnictví GP14-21095P GA ČR - Grantová agentura ČR Institucionální podpora MBU-M - RVO:61388971 ; FGU-C - RVO:67985823 ; UMG-J - RVO:68378050 UT WOS 000369481600024 EID SCOPUS 84953368007 DOI 10.1038/leu.2015.213 Anotace 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 strategy will 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. Treating leukemic 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-mTORC1 pathway, 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 inhibition of FAO significantly increased the sensitivity of ALL cells to ASNase. Moreover, constitutive activation of the mammalian target of rapamycin pathway increased apoptosis in leukemic cells treated with ASNase, but did not increase FAO. Our study uncovers a novel therapeutic option based on the combination of ASNase and FAO inhibitors Pracoviště Mikrobiologický ústav Kontakt Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Rok sběru 2016
Počet záznamů: 1