Malignant cells commonly use aerobic glycolysis for
ATP production; this is known as the Warburg effect, where
pyruvate is converted to
lactate, by
enzyme lactate dehydrogenase A (
LDH-A). In this study, we have investigated the effect of inhibition of
LDH-A on cells viability and identifying the mechanism of cell death in HeLa and MCF-7
cancer cells. Human
cervical cancer HeLa cell line and
breast cancer MCF-7 cell line were used to investigate the effect of inhibition of
LDH-A by
sodium oxamate on cell survival and proliferation using western blot, spectrophotometry, and immunofluorescent study. There was significant reduction in
LDH-A (P < 0.001) and cell viability (P < 0.001) in a dose-dependent mode in both HeLa and MCF-7 SO-treated
cancer cells. The
voltage-dependent anion channel (VDAC)
protein was significantly increased (P < 0.001) in association with decreased
LDH-A. The proapoptotic
proteins;
cytochrome C (P < 0.001), BAX (P < 0.001), cleaved
caspase-3 (P < 0.001), cleaved
caspase-8 (P < 0.001), and cleaved
caspase-9 (P < 0.001) were significantly increased in association with decreased
LDH-A. While, the
anti-apoptotic protein Bcl2 was significantly decreased (P < 0.001) in association with decreased
LDH-A. We conclude that Inhibition of
LDH-A can decrease cells viability through activation of intrinsic apoptotic pathway via increased VDAC
protein and inhibition of Bcl2 as well as activation of the extrinsic apoptotic pathway through activation of
caspase-8.