Erythritol (ERT) is a simple four-carbon sugar alcohol, that is produced endogenously via pentose phosphate pathway from glucose in all human cells mainly erythrocytes with a plasma level of ∼9.8 μM. It can be obtained exogenously from diets as an FDA-artificial sweetener. It possesses hydroxyl groups that are responsible for hydroxyl radical scavenging effect (antioxidant property). Recent studies have pointed out an ERT protection based on concentration dependant effect on endothelial cells. The protection includes surviving death under high glucose conditions in diabetic patients. In addition, ERT has been reported in pre-diagnostic serum samples of glioblastoma patients, which was elevated. It was not known whether ERT elevation was defensive or harmful. We studied the cytotoxic activity of ERT on brain tumor cell lines (U87, Daoy) using metabolic activity assay (MTT) with different erythritol concentrations. We observed that on high concentrations (2.87 M, 1.43 M, 0.72 M), there was a significant growth inhibition (P<0.05). On the other hand, lower concentrations (0.36 M, 8 mM, 4 mM, 2 mM, 0.8 mM, 36 µM, 8.2 µM, 4.1µM, 8.2nM), showed growth enhancement. ERT is known with its antioxidant effect in a concentration dependent manner. Therefore, we studied the antioxidant activity of ERT using ROS-Glo H₂O₂ Assay. We observed that on the high concentrations of ERT there was a significant decrease in hydrogen peroxide concentration to less than 50%, this suggests that ERT has antioxidant effect against hydrogen peroxide. In contrast, low ERT concentrations (around physiological level) showed significant enhancement to tumor growth (P<0.05). In conclusion, we found that erythritol plays an important role in brain cancer development and hydrogen peroxide regulation through a concentration dependant manner. Since ERT is found normally in human plasma, controlling ERT concentration will grant ERT the ability to work as therapeutic enhancer for brain cancer treatment or even a biomarker for prognosis.

Citation Format: Rayan Nassani, Hassan AlAmri, Bahauddeen M. Alrfaei. Erythritol acts as tumor enhancer and suppressor depending on concentrations in brain tumor cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB183.