Luteolin inhibits angiogenesis by blocking Gas6/Axl signaling pathway.
Int J Oncol
; 51(2): 677-685, 2017 Aug.
Article
em En
| MEDLINE
| ID: mdl-28627676
ABSTRACT
Growth arrest-specific protein 6 (Gas6) induces the activation of Axl receptor tyrosine kinase (Axl), which plays an important role in angiogenic processes, including proliferation, migration, invasion, tube formation and pericyte recruitment of endothelial cells. The inhibition of Gas6/Axl pathway has been demonstrated to be an effective anti-angiogenic therapy. Luteolin, which is a natural active flavonoid, has been reported to possess anti-angiogenic effects. However, the underlying mechanism of luteolin in anti-angiogenesis is not fully understood. Herein, we report that luteolin significantly inhibited the Gas6-induced proliferation, migration, invasion and tube formation of human microvascular endothelial cells (HMEC1s) in vitro, and suppressed the Gas6-induced recruitment of human brain vascular pericytes (HBVPs) to the endothelial tubes. Luteolin also suppressed Gas6-induced microvessel sprouting in aortic ring assay and neovascularization in chick chorioallantoic membrane assay. The anti-angiogenic effect of luteolin may be associated with the inhibition of the Gas6/Axl pathway and its downstream phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathways. Taken together, the present study provides new evidence regarding an anti-angiogenic mechanism of luteolin, and supports the notion that the dietary intake of luteolin contributes to the treatment of pathological angiogenesis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Proto-Oncogênicas
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Receptores Proteína Tirosina Quinases
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Peptídeos e Proteínas de Sinalização Intercelular
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Luteolina
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Neovascularização Patológica
Limite:
Animals
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Humans
Idioma:
En
Revista:
Int J Oncol
Ano de publicação:
2017
Tipo de documento:
Article