Metabolic Adjustments following Glutaminase Inhibition by CB-839 in Glioblastoma Cell Lines.

ABSTRACT: Most tumor cells can use glutamine (Gln) for energy generation and biosynthetic purposes. Glutaminases (GAs) convert Gln into glutamate and ammonium. In humans, GAs are encoded by two genes: GLS and GLS2. In glioblastoma, GLS is commonly overexpressed and considered pro-oncogenic. We studied the metabolic effects of inhibiting GLS activity in T98G, LN229, and U87MG human glioblastoma cell lines by using the inhibitor CB-839. We performed metabolomics and isotope tracing experiments using U-¹³C-labeled Gln, as well as ¹⁵N-labeled Gln in the amide group, to determine the metabolic fates of Gln carbon and nitrogen atoms. In the presence of the inhibitor, the results showed an accumulation of Gln and lower levels of tricarboxylic acid cycle intermedia

SUBMITTER: De Los Santos-Jimenez J 

PROVIDER: S-EPMC9856342 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature