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

• Published in: Leukemia research Vol. 22; no. 1; pp. 49 - 53
• Main Authors: Dittmann, Klaus H., Mayer, Claus, Rodemann, H.Peter, Petrides, Petro E., Denzlinger, Claudio
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 1998; Elsevier Science
• Subjects: Antineoplastic agents; apoptosis; Apoptosis - drug effects; Biological and medical sciences; Cell Division - drug effects; cell proliferation; cell survival; DNA Damage - drug effects; DNA Replication - drug effects; General aspects; HL-60 Cells - pathology; Humans; Indoles - pharmacology; leukemia; Leukotriene Antagonists; leukotrienes; Lipoxygenase Inhibitors - pharmacology; Medical sciences; Pharmacology. Drug treatments; TRIS, Tris (hydroxymethyl) aminomethane; leukemia; cell survival; BrdU, bromodeoxyuridine; cell proliferation; PDG, prostaglandin; PBS, phosphate buffered saline; apoptosis; leukotrienes; RT, room temperature; EDTA, ethylene diamine tetraacetate; Antineoplastic agent; Human; Promyelocytic leukemia; Cell proliferation; Enzyme; Arachidonic acid derivatives; Acute; Enzyme inhibitor; Malignant hemopathy; Biosynthesis; In vitro; HL60 cell line; Leukotriene B4; Cell death; Established cell line; Oxidoreductases; Inhibition; Lipoxygenase; Mechanism of action; Apoptosis
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/S0145-2126(97)00132-X

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.