PURPOSE: Recent studies have shown that brain tumor cells, unlike normal brain cells, are largely dependent upon glucose for energy and are not able to use ketone bodies as a primary energy source. These findings are thought to be because of decreased expression of succinyl-coenzyme A:3-oxoacid coenzyme A transferase (SCOT), a key enzyme involved in ketone body metabolism. Because of their neural crest origin, we hypothesized that neuroblastoma cells would also be unable to use ketone bodies as a primary energy source.

METHODS: Human foreskin fibroblasts (control) and human neuroblastoma cells (SK-N-AS) were grown in standard media with glucose (glc+), standard media without glucose (glc-), glucose-free media with acetoacetate, or glucose-free media with beta-hydroxybutyrate. Cell viability was determined with MTT [3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide] assay and apoptosis with fluorescence-activated cell sorting analysis. Immunoblotting was performed to SCOT protein.

RESULTS: Neuroblastoma cell viability was significantly decreased in the acetoacetate and hydroxybutyrate media by 52% and 61%, respectively, compared with control media. In addition, neuroblastoma cells showed significantly more apoptosis in the ketone media. Viability and apoptosis in the normal fibroblasts were not affected by the culture media. The expression of SCOT protein was significantly less in human neuroblastoma cells compared with the control fibroblasts.

CONCLUSIONS: Unlike human fibroblasts, neuroblastoma cells were unable to use ketone bodies as an energy source, likely because of their decreased expression of SCOT protein. Dietary manipulation using ketone bodies in accordance with SCOT expression may be a novel therapeutic strategy for neuroblastoma.

Interactions of the cell adhesion molecules are known to play important roles in mediating inflammation. The proinflammatory cytokine, tumor necrosis factor-α (TNF-α), activates the NF-kB signaling pathway, which induces the expression of various genes, such as intercellular adhesion molecule-1 (ICAM-1). In this study, the effect of vitamin C on the ICAM-1 expression induced by TNF-α in a human neuroblastoma cell line, SK-N-SH was investigated. Treatment with vitamin C resulted in the downregulation of the TNF-α-induced surface expression and ICAM-1 mRNA levels in a concentration-dependent manner. Moreover, a gel shift analysis indicated that vitamin C dose-dependently inhibited the NF-kB activation and lkBα degradation induced by TNF-α. Taken together, these results suggest that vitamin C downregulates TNF-α-induced ICAM-1 expression via the inhibition of NF-kB activation.