Millimolar concentrations of sodium ascorbate (vitamin C) induced apoptotic
cell death in human promyelocytic leukemic HL-60 cells. The apoptotic cell
s displayed a smaller cell volume, disappearance of cell surface microvilli
, appearance of cytoplasmic vacuoles, chromatin condensation, nuclear fragm
entation and production of apoptotic bodies. The apoptosis-inducing activit
y of sodium ascorbate was significantly enhanced by noncytotoxic concentrat
ions of CuCl2, but was almost completely eliminated by FeCl3. CuCl2 transie
ntly stimulated the hydrogen peroxide (H2O2) production by sodium ascorbate
, whereas FeCl3 slightly reduced the H2O2 production. alpha-Tocopherol (vit
amin E) slightly enhanced the radical and H2O2 productions, and apoptosis i
nduction by sodium ascorbate. The effect of alpha-tocopherol seems to be ra
ther specific for ascorbic acid since alpha-tocopherol did not significantl
y affect the cytotoxic activity of CuCl2 FeCl3 nor gallic acid. The present
study demonstrated the cooperative action of vitamins C and E.