Comparison of Spheroids Formed by Rat Glioma Stem Cells and Neural Stem Cells Reveals Differences in Glucose Metabolism and Promising Therapeutic Applications - Centre de recherche en cancérologie Nantes-Angers Unité Mixte de Recherche 892 Inserm - 6299 CNRS Accéder directement au contenu
Article Dans Une Revue Journal of Biological Chemistry Année : 2012

Comparison of Spheroids Formed by Rat Glioma Stem Cells and Neural Stem Cells Reveals Differences in Glucose Metabolism and Promising Therapeutic Applications

Résumé

Cancer stem cells (CSCs) are thought to be partially responsible for cancer resistance to current therapies and tumor recurrence. Dichloroacetate (DCA), a compound capable of shifting metabolism from glycolysis to glucose oxidation, via an inhibition of pyruvate dehydrogenase kinase was used. We show that DCA is able to shift the pyruvate metabolism in rat glioma CSCs but has no effect in rat neural stem cells. DCA forces CSCs into oxidative phosphorylation but does not trigger the production of reactive oxygen species and consecutive anti-cancer apoptosis. However, DCA, associated with etoposide or irradiation, induced a Bax-dependent apoptosis in CSCs in vitro and decreased their proliferation in vivo. The former phenomenon is related to DCA-induced Foxo3 and p53 expression, resulting in the overexpression of BH3-only proteins (Bad, Noxa, and Puma), which in turn facilitates Bax-dependent apoptosis. Our results demonstrate that a small drug available for clinical studies potentiates the induction of apoptosis in glioma CSCs.

Domaines

Cancer
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Origine : Publication financée par une institution

Dates et versions

inserm-03369867 , version 1 (07-10-2021)

Identifiants

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Marie Morfouace, Lisenn Lalier, Muriel Bahut, Virginie Bonnamain, Philippe Naveilhan, et al.. Comparison of Spheroids Formed by Rat Glioma Stem Cells and Neural Stem Cells Reveals Differences in Glucose Metabolism and Promising Therapeutic Applications. Journal of Biological Chemistry, 2012, 287, pp.33664. ⟨10.1074/jbc.m111.320028⟩. ⟨inserm-03369867⟩
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