Ketone bodies inhibit the viability of human neuroblastoma cells.
OBJECTIVE
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.
Skinner
Robert
R
Department of Surgery, University of Florida, Gainesville, 32608, USA.
Trujillo
Angelica
A
Ma
Xiaojie
X
Beierle
Elizabeth A
EA
D000214:Acyl Coenzyme A; D000704:Analysis of Variance; D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D066298:In Vitro Techniques; D007657:Ketone Bodies / Q000378:metabolism*; D009447:Neuroblastoma / Q000201:enzymology / Q000378:metabolism / Q000517:prevention & control*; D014407:Tumor Cells, Cultured
D000214:Acyl Coenzyme A; D007657:Ketone Bodies; C012046:succinyl-coenzyme A