MK-886 enhances tumour necrosis factor-alpha-induced differentiation and apoptosis.
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.
Stika
Jirí
J
Department of Comparative Animal Physiology and General Zoology, Faculty of Science, Masaryk University, CZ-611 37 Brno, Czech Republic.
Vondrácek
Jan
J
Hofmanová
Jirina
J
Simek
Vladimír
V
Kozubík
Alois
A
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
D001094:Arachidonate 5-Lipoxygenase; D007211:Indoles; D016859:Lipoxygenase Inhibitors; D014409:Tumor Necrosis Factor-alpha; C060893:MK-886; D002722:Chlorobenzenes