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

El Sayed, Salah Mohamed

doi:10.21608/svuijm.2024.288980.1858

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

Document Type : Original research articles

Author

Salah Mohamed El Sayed

Department of Clinical Biochemistry and Molecular Medicine, Taibah Faculty of Medicine, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia. & Department of Medical Biochemistry, Sohag Faculty of Medicine, Sohag University, Sohag, Egypt.

10.21608/svuijm.2024.288980.1858

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 H₂O₂production 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. H₂O₂was 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 H₂O₂at 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 H₂O₂production. Serial doses of pyruvate significantly and maximally scavenged C6 glioma-induced H₂O₂production.

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