Tracking the Aberrant Biochemistry in Glioblastoma Multiforme (GBM) and Neuroblastoma (NB) Using Nuclear Magnetic Resonance*

Glioblastoma multiforme (GBM) and neuroblastoma (NB) are aggressive cancers with distinct clinical profiles but shared metabolic dysregulation, offering a window into vulnerabilities that could revolutionize therapeutic strategies. Using nuclear magnetic resonance (NMR) spectroscopy and ¹³C-labeled tracers, this study unveils dynamic metabolic rewiring in GBM (U87) and NB (SK-N-SH) cell lines, exposing striking parallels and divergences in nutrient utilization. In GBM (U87) and NB (SK-N-SH) cells, short-term (1-hour) exposure to [1-¹³C]α-ketoisocaproate (KIC) led to rapid KIC accumulation, suggesting delayed breakdown. By 48 hours, KIC was recycled into leucine, a critical activator of cancer growth pathways like mTOR. Parallel experiments with [1-¹³C] glucose confirmed high glycolytic activity in both cancers, with NB cells showing stronger lactate production than GBM. Notably, ¹³C-glucose persisted at elevated levels, confirming heavy glucose reliance. These findings highlight two key metabolic strategies: (1) BCAA catabolism supports both energy production and growth signaling, and (2) glycolysis remains a dominant energy source, with NB exhibiting a more aggressive Warburg effect. This study provides direct evidence of metabolic rewiring in these cancers, pinpointing BCAA and glucose pathways as potential therapeutic targets.