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

Tae Young Kim, Joohye Kim, Hea Young Park Choo, Ho Jeong Kwon

Research output: Contribution to journalArticle

5 Citations (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.

Original languageEnglish
Pages (from-to)1117-1122
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume478
Issue number3
DOIs
Publication statusPublished - 2016 Jan 1

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Arachidonate 5-Lipoxygenase
Endothelial cells
Vascular Endothelial Growth Factor A
Endothelial Cells
Lipoxygenase Inhibitors
zileuton
Chorioallantoic Membrane
Vascular Endothelial Growth Factor Receptor-2
Phosphorylation
Angiogenesis Inhibitors
Leukotrienes
Extracellular Signal-Regulated MAP Kinases
Cell membranes
Drug Delivery Systems
Arachidonic Acid
Knockout Mice
Aneurysm
Neoplasms
Therapeutics
Asthma

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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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.",
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Inhibition of 5-lipoxygenase suppresses vascular endothelial growth factor-induced angiogenesis in endothelial cells. / Kim, Tae Young; Kim, Joohye; Choo, Hea Young Park; Kwon, Ho Jeong.

In: Biochemical and Biophysical Research Communications, Vol. 478, No. 3, 01.01.2016, p. 1117-1122.

Research output: Contribution to journalArticle

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