Cysteine dioxygenase 1 attenuates the proliferation via inducing oxidative stress and integrated stress response in gastric cancer cells.

ABSTRACT: Whereas cysteine dioxygenase 1 (CDO1) expression is lost due to its hypermethylated promoter across a range of cancer types including gastric cancer (GC), its functions and molecular underpinnings remain largely unknown. Here we demonstrate that reduced CDO1 expression is indicative of unfavorable prognosis in patients with GC. CDO1 overexpression in GC cells markedly inhibits cellular proliferation in vitro and in vivo. Mechanistically, CDO1 exerts this cytostatic effect via increasing oxidative stress and thus activating integrated stress response (ISR) in GC cells. High throughput screening (HTS) of antioxidants library identifies that Engeletin, a flavanonol glycoside, blunts oxidative stress and the ISR to relieve the inhibitory effect of CDO1 on the proliferation in GC cells. Additio

SUBMITTER: Ma G 

PROVIDER: S-EPMC9758200 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature