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

Abstract

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<0.001) compared to control. C6 glioma cells significantly induced the formation of H2O2 (measured in RFU) at the same different time points. H2O2 induced by the cancer cells was still significantly high (more than the baseline values upon adding serial doses of lactate). Serial doses of pyruvate significantly and maximally scavenged glioma-induced H2O2 production (p<0.001). Serial doses of lactate did not decrease H2O2 below the baseline values i.e. exogenous lactate did not scavenge H2O2. Conclusion: C6 glioma cells induce the formation of H2O2 at baseline and this decreased with adding the new culture medium at different sequential time points. 3BP induced the generation of H2O2 that persisted for at least two hours. Serial doses of lactate did not scavenge C6 glioma-induced H2O2 production. Serial doses of pyruvate significantly and maximally scavenged C6 glioma-induced H2O2 production.

Keywords

• lactate pyruvate c6 glioma h2o2 3-bromopyruvate