02197nas a2200289 4500008004100000022001400041245008700055210006900142260000800211300001400219490000800233520125800241653001401499653002301513653002501536653002001561653002801581653001001609100002901619700002501648700003001673700002001703700003101723700001701754700002101771856011501792 2018 eng d a0006-291X00aIntegrative analysis of rewired central metabolism in temozolomide resistant cells0 aIntegrative analysis of rewired central metabolism in temozolomi cJAN a2010-20160 v4953 a
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. (C) 2017 Elsevier Inc. All rights reserved.
10aGlutamine10aMetabolic rewiring10aMetabolite profiling10amRNA abundances10aTemozolomide resistance10aU87MG1 aImmanuel, Selva, Rupa C.1 aGhanate, Avinash, D.1 aParmar, Dharmeshkumar, S.1 aMarriage, Fiona1 aPanchagnula, Venkateswarlu1 aDay, Nap, J.1 aRaghunathan, Anu uhttp://library.ncl.res.in/content/integrative-analysis-rewired-central-metabolism-temozolomide-resistant-cells