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.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Stika J,Vondrácek J,Hofmanová J,Simek V,Kozubík A

doi

10.1016/j.canlet.2005.06.012

keywords:

subject

Has Abstract

pub_date

2006-06-18 00:00:00

pages

263-71

issue

2

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(05)00557-4

journal_volume

237

pub_type

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