Abstract
The lack of extracellular superoxide anion production by non-transformed cells prevents H2O2/peroxidase-mediated HOCl synthesis by these cells, as well as apoptosis induction by exogenous HOCl. In contrast, transformed cells generate extracellular superoxide anions and HOCl, and die by apoptosis after HOCl/superoxide-dependent hydroxyl radical generation at their membrane. Tumor cells prevent HOCl synthesis through expression of membrane-associated catalase, but their extracellular superoxide anions readily react with exogenous HOCl. The interaction between HOCl and H2O2 causes singlet oxygen generation that inactivates superoxide dismutase (SOD) on the surface of the tumor cells and thus enhances HOCl-mediated apoptosis through an increase in free superoxide anions. Higher concentrations of singlet oxygen inactivate membrane-associated catalase and thus lead to partial inhibition of apoptosis induction by exogenous HOCl, due to consumption of HOCl by H2O2. The data presented here show a complex, but coherent picture of interactions between defined reactive oxygen species and protective enzymes on the surface of tumor cells.