Altering the NAD+/NADH Ratio in Reprograms the Metabolome in Glioblastoma: Preclinical Findings

Synopsis

Glioblastoma multiforme (GBM) is the most aggressive and deadly form of brain cancer, known for its rapid growth and invasion into surrounding tissue. Because GBM cells rewire their metabolism to fuel constant energy production, researchers examined how changing the balance of NAD+ and NADH, two key molecules in cellular metabolism, affects tumor behavior. Using LbNOX, an enzyme that increases the NAD+/NADH ratio, scientists found that elevating this ratio reduced tumor cell invasion, lowered intracellular glutamate and calcium activity, and made the cancer less aggressive. Interestingly, neither blocking the mitochondrial electron transport chain nor supplementing nicotinamide riboside (NR)—a vitamin B3–derived NAD+ precursor—produced the same effect, showing that the balance between NAD+ and NADH, rather than total NAD+ levels, controls tumor invasiveness. These results point to the NAD+/NADH ratio as a promising new therapeutic target for limiting GBM spread and improving treatment outcomes.

Journal

Scientific Reports