Figure 7.

Acid accumulation in cells drives cancer cell death. (A) Partial inhibition of glycolysis with 2-deoxyglucose (2-DG) was able to reverse GYY4137 (400 μM)-induced cancer cell death in MCF7 and HepG2 cells. (B) Reversal of pH_i acidification using nigericin ionophore (Nig) resulted in increasing MCF7 and HepG2 cancer cell survival (left axis, bar chart) coupled with increasing pH_i (right axis, dot graph) (n = 3 for cell survival, n ≥ 30 cells per group for pH_i measurement). Results are mean ± SD. *P < 0.05 as compared to GYY4137-treated alone group. (C) Schematic diagram illustrating the potential of H₂S to alter glycolysis, impair pH balance and thence provoke cancer cell death. H₂S promotes an influx of glucose and triggers enhanced glycolysis. Overproduction of lactate, coupled with impaired activity of pH regulators results in accumulation of acid and reduction of pH_i. pH_i then serves as a stimulus to induce cancer cell death. AE, anion exchanger; GLUT, glucose transporter; HK, hexokinase; NHE, sodium/proton exchanger; PFK, phosphofructokinase; PK, pyruvate kinase.