MK-886, a leukotriene biosynthesis inhibitor, induces antiproliferative effects and apoptosis in HL-60 cells

MK-886, a specific inhibitor of 5-lipoxygenase inhibited DNA replication in leukemic HL-60 cells in a dose-dependent manner. Addition of exogenous leukotriene B-4 reversed this effect, whereas addition of leukotriene B-4 failed to modulate a prostaglandin D-2-induced inhibition of DNA replication. The reversal of MK-886-induced inhibition was not observed with leukotriene C-4. These results suggest that the effect of MK-886 is mediated by inhibition of leukotriene B-4 biosynthesis, Moreover, MK-886 not only impaired DNA replication in HL-60 cells but also decreased cell proliferation and induced apoptotic cell death. Our results suggest a crucial role of leukotriene B-4 in the regulation of cell proliferation and cell survival in HL-60 cells. (C) 1998 Elsevier Science Ltd. All rights reserved.