RT Conference Proceedings
T1 Metabolic changes upon GLS inhibition by CB-839 in glioma cell lines
A1 Santos Jiménez, Juan de los
A1 Rosales, Tracy
A1 Ko, Bookyung
A1 Márquez-Gómez, Javier
A1 Berardinis, Ralph J. de
A1 Mates-Sánchez, José Manuel
K1 Gliomas
K1 Cáncer
AB 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.
YR 2012
FD 2012-07-19
LK https://hdl.handle.net/10630/24923
UL https://hdl.handle.net/10630/24923
LA eng
NO Abcam Conference cancer and Metabolism 2022
NO Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026