Integrative analysis of rewired central metabolism in temozolomide resistant cells.
Biochem Biophys Res Commun
; 495(2): 2010-2016, 2018 01 08.
Article
en En
| MEDLINE
| ID: mdl-29248726
ABSTRACT
An authenticated U87MG clonal glioblastoma cell line was investigated to identify a sub-population of neurospheroidal (NSP) cells within the main epithelial population (U87MG). The NSP cells sorted using Fluorescence Assisted Cell Sorting (FACS) showed varied morphology, 30% lower growth rates, 40% higher IC50 values for temozolomide drug and could differentiate into the glial cell type (NDx). Metabolite profiling using HR-LCMS identified glucose, glutamine and serine in both populations and tryptophan only in U87MG as growth limiting substrates. Glycine, alanine, glutamate and proline were secreted by U87MG, however proline and glycine were re-utilized in NSP. Exo-metabolite profiling and phenotypic microarrays identified differential metabolism of primary carbon sources glucose and derived pyruvate for U87MG; glutamine and derived glutamate metabolism in NSP. Differential mRNA abundance of AKT1, PTEN, PIK3CA controlling metabolism, drug efflux, nutrient transport and epigenetic control MDM2 are potentially critical in shaping DNA methylation effects of temozolomide. Our study provides a new insight into the combined effect of these factors leading to temozolomide resistance in NSP.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Glioblastoma
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Ácido Pirúvico
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Dacarbazina
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Análisis de Flujos Metabólicos
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Aminoácidos
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Glucosa
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Año:
2018
Tipo del documento:
Article