3-bromopyruvate (3BP) is a promising anticancer drug that killed glioblastoma cells using different biochemical and pharmacological mechanisms e.g. inhibiting the glycolytic enzyme hexokinase II and inducing oxidative stress e.g. hydrogen peroxide generation. Glycolysis inhibition inactivates ABC transporters in cancer cells to restore the drug sensitivity in malignant cells. Moreover, the author and Japanese co-researchers proved that 3BP acts as an antimetabolite via antagonizing lactate (Warburg effect) and pyruvate and synergizing the anticancer effects of citrate. Interestingly, the author and Japanese co-researchers were the first to report that 3BP exerted potent anti-angiogenic effects. In this study, 3BP is structurally related to many different compounds that may affect its anticancer effects as pyruvate, lactate, acetic acid, L-alanine and beta-alanine. Author’s experimental data revealed that administering L-alanine alone caused a significant dose-dependent decrease (p<0.001) in C6 glioblastoma cells’ survival. This can be explained in light of the antioxidant merits exerted by the amino acid L-alanine. Unexpectedly, the structural analogs acetic acid, L-alanine and beta-alanine did not protect against 3BP-induced C6 glioma cell death. Treatment of C6 glioblastoma cells with hydrogen peroxide caused a significant glioblastoma cell death (p<0.001) that was significantly antagonized using the natural antioxidants e.g. pyruvate, reduced glutathione and N-acetyl L-cysteine (NAC) (p< 0.001). Lactate did not prevent or antagonize hydrogen peroxide-induced C6 glioma cell death. A combination of small doses of 3BP and citrate was synergistic in suppressing C6 spheroids viability. Moreover, 3BP induced C6 glioma protein depletion in a dose-dependent and time-dependent manner. Protein depletion was evident using SDS-PAGE and is thought to deprive the cancer cells from the necessary protein machineries for synthetic purposes. However, 3BP-induced protein depletion effects should be further studied on normal cells to prevent possible 3BP-induced side effects. Further studies are needed in this respect.

3-bromopyruvate, C6 glioblastoma, lactate, pyruvate, oxidative stress