Involvement of hydrogen peroxide and hydroxyl radical in chemically induced apoptosis of HL-60 cells.

Effects of three kinds of antagonists against reactive oxygen species were evaluated at the same time in chemically induced apoptosis of human leukemic HL-60 cells. Apoptosis of HL-60 cells induced by actinomycin D, H7, 1-beta-D-arabinofuranosylcytosine, and daunorubicin was inhibited significantly by radical scavengers (vitamin E, N-acetyl-L-cysteine, and mercaptoethanol), catalase, and a spin trap, N-t-butyl-alpha-phenylnitrone. These results suggest that hydrogen peroxide and hydroxyl radical are common mediators of apoptosis caused by these chemicals with apparently different functional mechanisms. The consumption of vitamin E to inhibit apoptosis induced by actinomycin D was undetectable, suggesting that the generation of reactive oxygen species during apoptosis was not very extensive. Radicals were suggested to be a mediator of apoptosis of HL-60 cells induced by cisplatin based on the observations that the above inhibitors, except catalase, effectively inhibited apoptosis by the drug.