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1.
Sci Rep ; 10(1): 20952, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33239671

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

2.
Sci Rep ; 10(1): 14072, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32826925

RESUMO

Altered metabolism of fatty acid synthesis is considered a hallmark characteristic of several malignancies, including acute lymphoblastic leukemia (ALL). To evaluate the impact of fatty acid synthase (FASN) on drug resistant ALL, bone marrow samples were collected from 65 pediatric ALLs, including 40 de novo and 25 relapsed patients. 22 non-cancer individuals were chosen as controls. Quantitative RT-PCR showed increased expression levels of FASN in drug resistant patients compared with the therapy responders. Single and combined treatment of malignant cells were analyzed using Annexin-V/PI double staining and MTT assays. Incubation of resistant primary cells with ginger showed simultaneous increased apoptosis rates and reduced FASN expression levels. Furthermore, docking studies demonstrated high affinity bindings between ginger derivatives and FASN thioesterase and ketosynthase domains, compared with their known inhibitors, fenofibrate and morin, respectively. Finally, combined treatment of in-house multidrug resistant T-ALL subline with ginger and dexamethasone induced drug sensitivity and down regulation of FASN expression, accordingly. To the best of our knowledge, this is the first study that introduces FASN upregulation as a poor prognostic factor for drug resistant childhood ALL. Moreover, it was revealed that FASN inhibition may be applied by ginger phytochemicals and overcome dexamethasone resistance, subsequently.


Assuntos
Ácido Graxo Sintase Tipo I/antagonistas & inibidores , Terapia de Alvo Molecular , Proteínas de Neoplasias/antagonistas & inibidores , Extratos Vegetais/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Zingiber officinale/química , Apoptose/efeitos dos fármacos , Medula Óssea/enzimologia , Estudos de Casos e Controles , Criança , Dexametasona/farmacologia , Dexametasona/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Indução Enzimática/efeitos dos fármacos , Feminino , Fenofibrato/farmacologia , Flavonoides/farmacologia , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Modelos Moleculares , Simulação de Acoplamento Molecular , Extratos Vegetais/farmacologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/enzimologia , Prognóstico , Conformação Proteica , Domínios Proteicos , RNA Mensageiro/biossíntese , RNA Neoplásico/biossíntese , Células Tumorais Cultivadas
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