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.