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Metabolic changes upon GLS inhibition by CB-839 in glioma cell lines
dc.contributor.author | Santos jiménez, Juan de los | |
dc.contributor.author | Rosales, Tracy | |
dc.contributor.author | Ko, Bookyung | |
dc.contributor.author | Márquez-Gómez, Javier | |
dc.contributor.author | Berardinis, Ralph J. de | |
dc.contributor.author | Mates-Sánchez, José Manuel | |
dc.date.accessioned | 2022-09-09T06:35:22Z | |
dc.date.available | 2022-09-09T06:35:22Z | |
dc.date.created | 2022-07-17 | |
dc.date.issued | 2012-07-19 | |
dc.identifier.citation | Abcam Conference cancer and Metabolism 2022 | es_ES |
dc.identifier.uri | https://hdl.handle.net/10630/24923 | |
dc.description.abstract | Many tumors use Gln for both energy generation and as a biosynthetic precursor. Glutaminases (GAs) catalyze the first step of glutaminolysis by converting glutamine (Gln) into glutamate and ammonia in the mitochondria. In humans, two genes encode for glutaminases: GLS and GLS2. We examined the metabolic consequences of inhibiting GLS activity in glioma cells by using the clinically relevant inhibitor CB-839. We treated three glioblastoma (GBM) cell lines with CB-839 and performed untargeted metabolomics and isotope tracing experiments using U-13C-labeled Gln and 15N-labeled Gln in the amido group to ascertain the metabolic fates of Gln carbon and nitrogen. Untargeted metabolomics results showed that CB-839 treatment significantly depleted tricarboxylic acid cycle (TCAC) intermediates and related metabolites in the three human glioblastoma cell lines assayed. This result was also confirmed by a lower labeling from U-13C- Gln in these metabolites. U-13C- Gln tracing also revealed reductive carboxylation-related labeling in these cell lines, and this pathways was also suppressed by CB-839. Metabolomics results showed an accumulation of the de novo purine biosynthesis intermediates inosine monophosphate and/or AICAR, and a decrease in uridine monophosphate, while 15N-Gln tracing results showed a decreased labeling from Gln amido group in AMP, GMP, UMP and CTP in T98G cell line when treated with CB-839. Finally, metabolomics showed higher levels of trimethyllysine and, in T98G cells, a 22-fold increase in 5-methyl-cytosine. | es_ES |
dc.description.sponsorship | Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. | es_ES |
dc.language.iso | eng | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.subject | Gliomas | es_ES |
dc.subject | Cáncer | es_ES |
dc.subject.other | Cancer | es_ES |
dc.subject.other | Metabolism | es_ES |
dc.subject.other | Metabolomics | es_ES |
dc.subject.other | Glioblastoma | es_ES |
dc.subject.other | Glutaminase | es_ES |
dc.title | Metabolic changes upon GLS inhibition by CB-839 in glioma cell lines | es_ES |
dc.type | info:eu-repo/semantics/conferenceObject | es_ES |
dc.centro | Facultad de Ciencias | es_ES |
dc.relation.eventtitle | Abcam Conference Cancer and Metabolism 2022 | es_ES |
dc.relation.eventplace | London, UK | es_ES |
dc.relation.eventdate | 17-19 Julio 2022 | es_ES |