%20shows%20progressive%20loss%20of%20SIRT3,%20a%20mitochondrial%20deacetylase%20whose%20downregulation%20correlates%20with%20poor%20patient%20survival.%20Using%20spontaneous%20and%20expe...){kind=link}
Nicotinamide Riboside Prevents and Enhances Therapy in Pancreatic Ductal Adenocarcinoma: Preclinical Findings
Synopsis
Pancreatic ductal adenocarcinoma (PDAC) shows progressive loss of SIRT3, a mitochondrial deacetylase whose downregulation correlates with poor patient survival. Using spontaneous and experimental PDAC models, this study demonstrates that SIRT3 deficiency accelerates premalignant lesion formation, while nicotinamide riboside (NR) restores SIRT3 expression and activates its mitochondrial regulatory network, including metabolic enzymes and respiratory chain components. NR delayed PDAC carcinogenesis, suppressing progression of early lesions. In addition, NR enhanced gemcitabine chemosensitivity, synergistically increasing tumor cell death in vitro and in vivo. These findings establish NR as a dual-function therapeutic: it prevents PDAC development and strengthens chemotherapy efficacy by restoring SIRT3-driven mitochondrial homeostasis, offering a promising strategy to overcome PDAC therapeutic resistance.
Journal
Biochemical Pharmacology