Time-dependent biochemical effects of the promising anticancer drug 3-bromopyruvate and its biochemical analogs pyruvate and lactate (Warburg effect) on C6 glioma-induced H2O2 production

Background: Pyruvate (an antioxidant) result from aerobic glucose oxidation (aerobic glycolysis) while lactate (a pro-oxidant metabolite in the tumor microenvironment) results from anaerobic glycolysis. Lactate is a structural analog to pyruvate (formed in anaerobic conditions via adding two hydrogen atoms to pyruvate carried on the coenzyme NADH.H) via the enzyme lactate dehydrogenase. Both pyruvate and lactate are structural analogs of the promising anticancer drug 3-bromopyruvate (3BP). 3BP acts via competing with lactate and pyruvate. Objectives: To investigate if H2O2 production is induced by C6 glioma cells and added 3BP at different time points and the effects of serial doses of exogenous lactate and pyruvate on H2O2. Materials and methods: C6 glioma cells were cultured till reaching confluency and fresh medium containing the scheduled treatments was added. H2O2 was assayed (30, 45, 60 and 120 minutes later). Results: The author confirmed his previous findings that 3BP significantly induced H2O2 production (that persisted over these different time points) (p