Increasing NAD+ with Nicotinamide Riboside Prevents Liver Cancer Driven by URI: Preclinical Findings

Synopsis

The molecular causes of liver cancer (hepatocellular carcinoma, HCC) are not fully understood. This study used genetically modified mice to show that when liver cells produce too much of a protein called URI, it triggers a multi-step process leading to HCC. Reducing URI in liver cells protects against chemically induced liver cancer. URI blocks certain enzymes involved in breaking down L-tryptophan and producing NAD+, which leads to DNA damage early in tumor development. Giving nicotinamide riboside (NR) to restore NAD+ levels prevented DNA damage and tumor formation. In human liver cancer, high URI levels are linked to worse survival and lower activity in the tryptophan/NAD+ pathway. These findings suggest that boosting NAD+ with compounds like NR could help prevent or treat liver cancer.

Journal

Cancer Cell