Efficacy of Dual Inhibition of Glycolysis and Glutaminolysis for Therapy of Renal Lesions in Tsc2^+/- Mice.

ABSTRACT: Tuberous sclerosis is caused by mutations in the TSC1 or TSC2 gene and characterized by development of tumors in multiple organs including the kidneys. TSC-associated tumors exhibit somatic loss of the second allele of the TSC genes, leading to aberrant activation of the mechanistic target of rapamycin (mTOR) signaling pathway. Activation of mTOR complex 1 (mTORC1) causes addiction to glucose and glutamine in Tsc1^-/-or Tsc2^-/- mouse embryonic fibroblasts (MEFs). Blocking of glutamine anaplerosis in combination with glycolytic inhibition causes significant cell death in Tsc2^-/- but not Tsc2^+/+ MEFs. In this study, we tested efficacy of dual inhibition of glycolysis with 3-BrPA and glutaminolysis with CB-839 for renal tumors in Tsc2^+/- m

SUBMITTER: Jones AT 

PROVIDER: S-EPMC6324218 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature