VDAC1-interacting molecules promote cell death in cancer organoids through mitochondrial-dependent metabolic interference.

ABSTRACT: The voltage-dependent anion-selective channel isoform 1 (VDAC1) is a pivotal component in cellular metabolism and apoptosis with a prominent role in many cancer types, offering a unique therapeutic intervention point. Through an in-silico-to-in-vitro approach we identified a set of VA molecules (VDAC Antagonists) that selectively bind to VDAC1 and display specificity toward cancer cells. Biochemical characterization showed that VA molecules can directly interact with VDAC1 with micromolar affinity by competing with the endogenous ligand NADH for a partially shared binding site. NADH displacement results in mitochondrial distress and reduced cell proliferation, especially when compared to non-cancerous cells. Experiments performed on organoids derived from intrahepatic cholang

SUBMITTER: Conti Nibali S 

PROVIDER: S-EPMC11112339 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature