The glutamine antagonist prodrug JHU-083 slows malignant glioma growth and disrupts mTOR signaling.

ABSTRACT:

Background

Metabolic reprogramming is a common feature in cancer, and it is critical to facilitate cancer cell growth. Isocitrate Dehydrogenase 1/2 (IDH1 and IDH2) mutations (IDHmut) are the most common genetic alteration in glioma grade II and III and secondary glioblastoma and these mutations increase reliance on glutamine metabolism, suggesting a potential vulnerability. In this study, we tested the hypothesis that the brain penetrant glutamine antagonist prodrug JHU-083 reduces glioma cell growth.

Material and methods

We performed cell growth, cell cycle, and protein expression in glutamine deprived or Glutaminase (GLS) gene silenced glioma cells. We tested the effect of JHU-083 on cell proliferation, metabolism, and mTOR signaling in c

SUBMITTER: Yamashita AS 

PROVIDER: S-EPMC7920530 | biostudies-literature | 2021 Jan-Dec

REPOSITORIES: biostudies-literature