Differential involvement of Caspases in hydroquinone-induced apoptosis in human leukemic HL-60 and Jurkat cells

The benzene metabolite hydroquinone (HQ) is postulated to exert its myeloto xicity by bioactivation to reactive quinone derivatives in myeloperoxidase (MPO)-containing cells. In this study, the role of caspases in hydroquinone -induced apoptosis in MPO-rich HL-60 promyelocytic leukemia and MPO-deficie nt Jurkat T-lymphoblastic leukemia cells was investigated. HQ-induced apopt osis in both cell types was accompanied by phosphatidylserine (PS) exposure , caspases-3/-7 activation, PAR-P cleavage, DNA fragmentation, and ultrastr uctural changes as assessed by electron microscopy. In HL-60 cells, the gen eral caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone (Z -VAD.FMK) blocked activation of caspases-3/-7, cleavage of PARP, and DNA, b ut PS externalization and cytoplasmic changes were not significantly affect ed. In marked contrast, all features of apoptosis were completely inhibited by Z-VAD.FMK in HQ-treated Jurkat cells. These data provide evidence for Z -VAD.FMK-insensitive and caspases-3/4-independent pathway(s) in the externa lization of PS and cytoplasmic changes during HQ-induced apoptosis in HL-60 cells. In contrast, in Jurkat cells, all of these changes required caspase activation. The ability of HQ to induce equivalent apoptosis in both MPO-d eficient Jurkat cells and MPO-rich HL-60 cells demonstrates that MPO-cataly zed bioactivation of HQ is not a prerequisite for toxicity. The differentia l mechanisms of apoptosis in HL-60 and Jurkat T cells may reflect the MPO a ctivity of these cells and, as a result, the amount of reactive BQ and othe r metabolites that are generated. (C) 2001 Academic Press.