In Vitro Effect of Ketogenic Diet on Ewing Sarcoma Cells
The Ketogenic Diet (KD) is a high-fat, low-carbohydrate diet that lowers blood glucose levels while increasing ketone bodies, such as Beta-hydroxybutyrate (BHB), which is the most abundant ketone found in the bloodstream and an effective source of energy when glucose is not available. The ketogenic diet can promote weight loss, be adapted for sports enhancement and be used as a cancer treatment. Most cancer cells utilize glucose as their primary energy source while normal healthy cells can also efficiently utilize ketones. Recently, the genes OXCT1 and BDH1 were described potential biomarkers for KD sensitivity. Analysis of gene expression data of pediatric solid tumors showed that Ewing sarcoma (ES) cells have lower levels of both of these markers. ES is a soft tissue cancer that affects children and teenagers, and is typically found in the long bones or tissues around the bones. In this project, we looked at the effects of BHB on growth of ES cells as a preliminary evaluation of using KD for the treatment of ES. We investigated the basal expression levels of both OXCT1 and BDH1 in four ES cell lines TC-32, TC-71, RD-ES and SK-ES-1, as well as control lines HeLa and Panc1. Results showed that the ES cell lines expressed low amounts of OXCT1, but higher amounts of BDH1 compared to the HeLa control. ES cells were also grown in media containing low glucose or high glucose and treated with various doses of BHB for either 72 or 96 hours. Results showed that three of the four ES cells grew better in low glucose media, but the response to BHB was similar in either media. The results demonstrated that BHB does have a growth inhibiting effect on ES cells. Taken together, these results support the need for further research on the effects of the ketogenic diet on ES cells and could lead to an improved form of therapy for patients with this disease.