Global metabolic profile identifies choline kinase alpha as a key regulator of glutathione-dependent antioxidant cell defense in ovarian carcinoma.

ABSTRACT: Epithelial Ovarian Cancer (EOC) "cholinic phenotype", characterized by increased intracellular phosphocholine content sustained by over-expression/activity of choline kinase-alpha (ChoKα/CHKA), is a metabolic cellular reprogramming involved in chemoresistance with still unknown mechanisms.By stable CHKA silencing and global metabolic profiling here we demonstrate that CHKA knockdown hampers growth capability of EOC cell lines both in vitro and in xenotransplant in vivo models. It also affected antioxidant cellular defenses, decreasing glutathione and cysteine content while increasing intracellular levels of reactive oxygen species, overall sensitizing EOC cells to current chemotherapeutic regimens. Natural recovering of ChoKα expression after its transient silencing rescued the wild-type p

SUBMITTER: Granata A 

PROVIDER: S-EPMC4484451 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature