Treatment with 0.2 mM
hydrogen peroxide (H(2)O(2)) or with 0.5 mM
cisplatin caused
caspase-9 and
caspase-3 activation and death by apoptosis in U-937 human promonocytic cells. However, treatment with 2 mM H(2)O(2), or incubation with the
glutathione suppressor DL-
buthionine-(S,R)-sulfoximine (BSO) prior to treatment with
cisplatin, suppressed
caspase activation and changed the mode of death to
necrosis. Treatment with 2 mM H(2)O(2) caused a great decrease in the intracellular
ATP level, which was partially prevented by
3-aminobenzamide (3-ABA). Correspondingly, 3-ABA restored the activation of
caspases and the execution of apoptosis. By contrast, BSO plus
cisplatin did not decrease the
ATP levels, and the generation of
necrosis by this treatment was not affected by 3-ABA. On the other hand, while all apoptosis-inducing treatments and treatment with 2 mM H(2)O(2) caused Bax translocation from the cytosol to mitochondria as well as
cytochrome c release from mitochondria to the cytosol, treatment with BSO plus
cisplatin did not. Treatment with
cisplatin alone caused Bid cleavage, while BSO plus
cisplatin as well as 0.2 and 2 mM H(2)O(2) did not. Bcl-2 overexpression reduced the generation of
necrosis by H(2)O(2), but not by BSO plus
cisplatin. These results indicate the existence of different apoptosis/
necrosis regulatory mechanisms in promonocytic cells subjected to different forms of oxidative stress.