Nicotinamide riboside enhances the efficacy of gemcitabine and suppresses PDAC premalignant lesions via SIRT3 activation.
Nicotinamide riboside may enhance the effectiveness of chemotherapy and delay tumor progression in pancreatic cancer models, but direct implications for human treatment remain unclear.
Where it sits
this study against the rest of the nad+ (nicotinamide adenine dinucleotide) corpusSummary and findings
This study investigates the effects of nicotinamide riboside (NR), a NAD+ precursor, on pancreatic ductal adenocarcinoma (PDAC) by assessing its role in enhancing chemosensitivity and suppressing tumor progression. The research includes multi-level clinical analyses and spontaneous PDAC models. Not reported in abstract.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains a lethal malignancy with limited therapeutic options. This study identifies nicotinamide riboside (NR), a natural NAD<sup>+</sup> precursor, as a dual-function agent that enhances chemosensitivity and suppresses tumor progression by activating the mitochondrial deacetylase sirtuin 3 (SIRT3). Multi-level clinical analyses revealed progressive SIRT3 downregulation in PDAC pathogenesis, correlating with poor survival. Genetic ablation of SIRT3 accelerated premalignant lesions in spontaneous models, whereas NR administration restored SIRT3 expression and activated its mitochondrial regulatory network, comprising key metabolic enzymes and respiratory chain components, in a SIRT3-dependent manner. In spontaneous PDAC models, NR monotherapy delayed carcinogenesis by suppressing the progression of premalignant lesions. Moreover, NR significantly potentiated gemcitabine efficacy both in vitro and in subcutaneous PDAC models, demonstrating synergistic enhancement of chemotherapy-induced tumor cell death. These findings establish NR as a promising SIRT3-targeting adjuvant that both enhances the efficacy of standard chemotherapy and delays carcinogenesis, thereby overcoming therapeutic resistance in established PDAC and potentially impeding its development.
Background
The paper addresses the potential role of nicotinamide riboside in enhancing chemotherapy efficacy and its impact on PDAC premalignant lesions. Prior research has suggested that SIRT3 may play a role in cancer metabolism and progression. This study is significant as it explores a novel approach to improve treatment outcomes in PDAC.
Methods
Not reported in abstract.
Results
Not reported in abstract.
Interpretation
Not reported in abstract.
Key findings
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Limitations
- Not reported in abstract.