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 B4 reversed this effect, whereas addition of leukotriene B4 failed to modulate a prostaglandin D2-induced inhibition of DNA replication. The reversal of MK-886-induced inhibition was not observed with leukotriene C4. These results suggest that the effect of MK-886 is mediated by inhibition of leukotriene B4 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 B4 in the regulation of cell proliferation and cell survival in HL-60 cells.
Dittmann
K H
KH
Department of Radiotherapy, University of Tübingen, Germany.
Mayer
C
C
Rodemann
H P
HP
Petrides
P E
PE
Denzlinger
C
C
D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D018922:HL-60 Cells / Q000473:pathology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D020024:Leukotriene Antagonists; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D002722:Chlorobenzenes
D007211:Indoles; D020024:Leukotriene Antagonists; D016859:Lipoxygenase Inhibitors; C060893:MK-886; D002722:Chlorobenzenes