Sesamin Attenuates VEGFA-Induced Angiogenesis via Inhibition of Src and FAK Signaling in Chick Chorioallantoic Membrane Model and Human Endothelial EA.hy926 Cells

芝麻素通过抑制鸡胚绒毛尿囊膜模型和人内皮细胞 EA.hy926 中的 Src 和 FAK 信号传导减弱 VEGFA 诱导的血管生成

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作者:Tanyaporn Keratibumrungpong, Warunee Srisuthtayanont, Orawan Wanachewin, Jeerawan Klangjorhor, Thanyaluck Phitak, Peraphan Pothacharoen, Thuzar Hla Shwe, Prachya Kongtawelert

Abstract

Sesamin, a major phytochemical in sesame seeds and oil, has been reported to have effects on physiological and pathological angiogenesis in several studies. Nevertheless, the underlying mechanisms of sesamin's effect on angiogenesis are not understood well enough. This study aimed to investigate its effect on both physiological and pathological angiogenesis using the in vivo chick chorioallantoic membrane (CAM) model and the in vitro human endothelial cell line, EA.hy926, model. Sesamin inhibited the VEGFA-induced pathological angiogenesis significantly, although no effect was seen on angiogenesis without induction. It reduced the formation of vascular branches in the VEGFA-treated CAMs and also the proliferation and migration of EA.hy926 endothelial cells induced by VEGFA. Sesamin impeded the VEGF-mediated activation of Src and FAK signaling proteins, which may be responsible for sesamin-mediated reduction of pathological angiogenesis. Moreover, the effect of sesamin on the expressions of angiogenesis-related genes was then investigated and it was found that both mRNA and protein expressions of Notch1, the key pathway in vascular development, induced by VEGFA, were significantly reduced by sesamin. Our results altogether suggested that sesamin, by inhibiting pathological angiogenesis, has the potential to be employed in the prevention or treatment of diseases with over-angiogenesis, such as cancers.

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