A synthetic lethal drug combination mimics glucose deprivation-induced cancer cell death in the presence of glucose.

ABSTRACT: Metabolic reprogramming in cancer cells can increase their dependence on metabolic substrates such as glucose. As such, the vulnerability of cancer cells to glucose deprivation creates an attractive opportunity for therapeutic intervention. Because it is not possible to starve tumors of glucose in vivo, here we sought to identify the mechanisms in glucose deprivation-induced cancer cell death and then designed inhibitor combinations to mimic glucose deprivation-induced cell death. Using metabolomic profiling, we found that cells undergoing glucose deprivation-induced cell death exhibited dramatic accumulation of intracellular l-cysteine and its oxidized dimer, l-cystine, and depletion of the antioxidant GSH. Building on this observation, we show that glucose deprivation-induced cell

SUBMITTER: Joly JH 

PROVIDER: S-EPMC6996897 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature