title: MK-886 enhances tumour necrosis factor-alpha-induced differentiation and apoptosis.
abstract: We investigated the role of the 5-lipoxygenase (5-LOX) pathway of arachidonic acid metabolism in tumour necrosis factor-alpha (TNF-alpha)-induced differentiation of human leukemic HL-60 cells using MK-886, an inhibitor of 5-LOX activating protein. MK-886 augmented cell cycle arrest and differentiation induced by TNF-alpha; however, both effects were probably 5-LOX-independent, because a general LOX inhibitor, NDGA, had no effect. Apoptosis was significantly elevated after combined TNF-alpha and MK-886 treatment, which could be partially associated with changes of Mcl-1 protein expression. NF-kappaB signalling or activation of JNKs were not modulated by MK-886. Thus, in addition to apoptosis, MK-886 can enhance TNF-alpha-induced differentiation.
authors.affiliation: Department of Comparative Animal Physiology and General Zoology, Faculty of Science, Masaryk University, CZ-611 37 Brno, Czech Republic.
authors.forename: Jirí
authors.initials: J
authors.lastname: Stika
authors.forename: Jan
authors.initials: J
authors.lastname: Vondrácek
authors.forename: Jirina
authors.initials: J
authors.lastname: Hofmanová
authors.forename: Vladimír
authors.initials: V
authors.lastname: Simek
authors.forename: Alois
authors.initials: A
authors.lastname: Kozubík
mesh_terms: D017209:Apoptosis; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D002453:Cell Cycle; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002470:Cell Survival; D018922:HL-60 Cells; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D015398:Signal Transduction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D002722:Chlorobenzenes
chemical_list: D001094:Arachidonate 5-Lipoxygenase; D007211:Indoles; D016859:Lipoxygenase Inhibitors; D014409:Tumor Necrosis Factor-alpha; C060893:MK-886; D002722:Chlorobenzenes