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Inhibition of 5-lipoxygenase suppresses vascular endothelial growth factor-induced angiogenesis in endothelial cells

Title
Inhibition of 5-lipoxygenase suppresses vascular endothelial growth factor-induced angiogenesis in endothelial cells
Authors
Kim, Tae YoungKim, JoohyeChoo, Hea-Young ParkKwon, Ho Jeong
Ewha Authors
박혜영
SCOPUS Author ID
박혜영scopus
Issue Date
2016
Journal Title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
ISSN
0006-291XJCR Link1090-2104JCR Link
Citation
vol. 478, no. 3, pp. 1117 - 1122
Keywords
5-LipoxygenaseAnti-angiogenic effectsVascular endothelial growth factor signaling
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
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.
DOI
10.1016/j.bbrc.2016.08.078
Appears in Collections:
약학대학 > 약학과 > Journal papers
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