title: MK-886, a leukotriene biosynthesis inhibitor, induces antiproliferative effects and apoptosis in HL-60 cells.
abstract: 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.
authors.affiliation: Department of Radiotherapy, University of Tübingen, Germany.
authors.forename: K H
authors.initials: KH
authors.lastname: Dittmann
authors.forename: C
authors.initials: C
authors.lastname: Mayer
authors.forename: H P
authors.initials: HP
authors.lastname: Rodemann
authors.forename: P E
authors.initials: PE
authors.lastname: Petrides
authors.forename: C
authors.initials: C
authors.lastname: Denzlinger
mesh_terms: 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
chemical_list: D007211:Indoles; D020024:Leukotriene Antagonists; D016859:Lipoxygenase Inhibitors; C060893:MK-886; D002722:Chlorobenzenes