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Updated: Jun 26, 2026
Differentiation of the SH-SY5Y Human Neuroblastoma Cell Line
Published on: February 17, 2016
Ketone bodies inhibit the viability of human neuroblastoma cells
Robert Skinner1, Angelica Trujillo, Xiaojie Ma
1Department of Surgery, University of Florida, Gainesville, 32608, USA.
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.
Insights
Neuroblastoma cells cannot metabolize ketone bodies for energy due to low succinyl-coenzyme A:3-oxoacid coenzyme A transferase (SCOT) expression. This suggests ketone-based dietary strategies may offer a novel neuroblastoma treatment.
Area of Science:
- Biochemistry
- Oncology
- Metabolic Research
Background:
- Brain tumor cells primarily rely on glucose and cannot efficiently metabolize ketone bodies.
- This metabolic difference is attributed to reduced expression of succinyl-coenzyme A:3-oxoacid coenzyme A transferase (SCOT).
- Neuroblastoma, originating from neural crest cells, shares metabolic similarities with brain tumors.
Purpose of the Study:
- To investigate if neuroblastoma cells, similar to brain tumors, are unable to utilize ketone bodies for energy.
- To determine the role of SCOT protein expression in neuroblastoma's ketone body metabolism.
- To explore the potential of ketone bodies as a therapeutic strategy for neuroblastoma.
Main Methods:
- Human neuroblastoma cells and fibroblasts were cultured in glucose-rich, glucose-free, and ketone body-supplemented media.
- Cell viability was assessed using MTT assay, and apoptosis was quantified via fluorescence-activated cell sorting.
- Succinyl-coenzyme A:3-oxoacid coenzyme A transferase (SCOT) protein levels were analyzed using immunoblotting.
Main Results:
- Neuroblastoma cells exhibited significantly reduced viability (52-61%) and increased apoptosis when cultured in ketone body-supplemented media.
- Normal fibroblasts showed no significant changes in viability or apoptosis across different media conditions.
- Neuroblastoma cells displayed markedly lower SCOT protein expression compared to control fibroblasts.
Conclusions:
- Neuroblastoma cells are metabolically incapable of using ketone bodies as an energy source, primarily due to diminished SCOT expression.
- This metabolic vulnerability suggests that dietary interventions involving ketone bodies could be a promising therapeutic avenue for neuroblastoma.
- Further research into SCOT expression and ketone metabolism may lead to novel treatment strategies for neuroblastoma.
