Tumor cells often exhibit an altered metabolic phenotype. However, it is unclear as to when this switch takes place in
ovarian cancer, and the potential for these changes to serve as therapeutic targets in clinical prevention and intervention trials. We used our recently developed and characterized mouse ovarian surface epithelial (
MOSE)
cancer progression model to study metabolic changes in distinct disease stages. As
ovarian cancer progresses, complete oxidation of
glucose and
fatty acids were significantly decreased, concurrent with increases in
lactate excretion and (3)H-deoxyglucose uptake by the late-stage
cancer cells, shifting the cells towards a more glycolytic phenotype. These changes were accompanied by decreases in TCA flux but an increase in
citrate synthase activity, providing substrates for de novo
fatty acid and
cholesterol synthesis. Also, uncoupled maximal respiration rates in mitochondria decreased as
cancer progressed. Treatment of the
MOSE cells with 1.5 μM
sphingosine, a bioactive
sphingolipid metabolite, decreased
citrate synthase activity, increased TCA flux, decreased
cholesterol synthesis and glycolysis. Together, our data confirm metabolic changes during
ovarian cancer progression, indicate a stage specificity of these changes, and suggest that multiple events in cellular metabolism are targeted by exogenous
sphingosine which may be critical for future prevention trials.