Energy and endoplasmic reticulum stress induction by gold(III) dithiocarbamate and 2-deoxyglucose synergistically trigger cell death in breast cancer.

ABSTRACT: The elusiveness of triple-negative breast cancer from targeted therapy has redirected focus toward exploiting the metabolic shortcomings of these highly metastatic subtypes of breast cancer. Cueing from the metabolic heterogeneity of TNBC and the exposition of the dual dependence of some TNBCs on OXPHOS and glycolysis for ATP, we herein report the efficacy of cotreatment of TNBCs with an OXPHOS inhibitor, 2a and 2DG, a potent glycolysis inhibitor. 2a-2DG cotreatment inhibited TNBC cell proliferation with IC₅₀ of ∼5 to 36 times lower than that of 2a alone and over 5000 times lower than IC₅₀ of 2DG alone. 2a-2DG cotreatment suppressed mitochondrial ATP production and significantly induced AMPK activation. Mechanistic studies revealed the distinct yet synergistic contrib

SUBMITTER: Orobator ON 

PROVIDER: S-EPMC11647619 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature