Inhibition of Anaplerotic Glutaminolysis Underlies Selenite Toxicity in Human Lung Cancer.

ABSTRACT: Large clinical trials and model systems studies suggest that the chemical form of selenium dictates chemopreventive and chemotherapeutic efficacy. Selenite induces excess ROS production, which mediates autophagy and eventual cell death in non-small cell lung cancer adenocarcinoma A549 cells. As the mechanisms underlying these phenotypic effects are unclear, the clinical relevance of selenite for cancer therapy remains to be determined. The authors' previous stable isotope-resolved metabolomics and gene expression analysis showed that selenite disrupts glycolysis, the Krebs cycle, and polyamine metabolism in A549 cells, potentially through perturbed glutaminolysis, a vital anaplerotic process for proliferation of many cancer cells. Herein, the role of the glutaminolytic enzyme glutaminase 1

SUBMITTER: Bruntz RC 

PROVIDER: S-EPMC7153719 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature