Transformed target cell-derived superoxide anions drive apoptosis induction by myeloperoxidase

Myeloperoxidase induces apoptosis in src- or ras-transformed fibroblasts, but not in parental nontransformed fibroblasts. This selectivity seems to be based on superoxide anion production by transformed cells, a recently described characteristic feature of transformed cells. Myeloperoxidase mediated apoptosis induction is inhibited by SOD, catalase, 4-aminobenzoyl hydrazide, taurine and DMSO. This pattern of inhibition allows us to conclude that transformed cell derived superoxide anions dismutate to hydrogen peroxide, which fosters HOCl formation by myeloperoxidase. Hydrogen peroxide formation thereby is the rate-limiting step and depends on the cell density. In a second step, HOCl interacts with superoxide anions to yield the highly reactive apoptosis inducing hydroxyl radical. This conclusion was verified through selective apoptosis induction in transformed cells by direct addition of HOCl, which was also inhibited by SOD and DMSO. Our findings demonstrate a specific interplay between target cell derived superoxide anions and MPO during selective apoptosis induction.