کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5506705 1400302 2016 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Inhibition of 5-lipoxygenase suppresses vascular endothelial growth factor-induced angiogenesis in endothelial cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Inhibition of 5-lipoxygenase suppresses vascular endothelial growth factor-induced angiogenesis in endothelial cells
چکیده انگلیسی
5-Lipoxygenase (5-LOX) is an enzyme that converts arachidonic acid from the cell membrane into leukotriene, a signal lipid mediator. 5-LOX deficiency markedly attenuates the formation of aneurysms in knockout mice. In addition, Zileuton, a clinical drug targeting 5-LOX, is used for treatment of asthma. However, it is unclear whether 5-LOX inhibition results in anti-angiogenic effects for applications in cancer therapy. To explore the roles of 5-LOX in angiogenesis and its potential as a therapeutic target in cancer, the effects of a newly synthesized 5-LOX inhibitor, F3, on in vitro and in vivo angiogenesis were investigated. The results showed that 5-LOX inhibition by F3 suppressed in vitro vascular endothelial growth factor (VEGF)-induced tube formation and chemo-invasion of endothelial cells (ECs). 5-LOX inhibition also decreased VEGF-induced extracellular signal-regulated kinase (ERK) phosphorylation in ECs. Notably, 5-LOX knockdown phenocopied the anti-angiogenic activity of the 5-LOX inhibitor F3 in a concentration-dependent manner. F3 did not affect the activities of VEGF receptor 2 or AKT. In vivo, the compound significantly inhibited the formation of the chorioallantoic membrane at nontoxic doses. These results demonstrated that 5-LOX played an important role in angiogenesis and that its inhibitor F3 could be a new anti-angiogenic agent targeting VEGF signaling.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 478, Issue 3, 23 September 2016, Pages 1117-1122
نویسندگان
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