Sanguinarine inhibits VEGF-induced Akt phosphorylation

Sanguinarine inhibits VEGF-induced Akt phosphorylation
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DOI:
10.1196/annals.1397.040
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发表时间:
2007-01-01
期刊:
SIGNAL TRANSDUCTION PATHWAYS, PT C
影响因子:
--
通讯作者:
Grasselli, Francesca
Grasselli, Francesca
中科院分区:
其他
文献类型:
--
作者:
Basini, Giuseppina;Santini, Sujen Eleonora;Grasselli, Francesca

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血管生成是通过预先存在的血管的发芽而进行的血管生长的过程。这一过程对许多重要的疾病状态有显著影响,包括癌症、糖尿病视网膜病变和关节炎。内皮细胞从它们的环境接收多种信息,这导致它们沿着新血管形成的所有阶段前进沿着。血管内皮生长因子(VEGF),特别是似乎是这个过程的主要调节。该分子与细胞受体相互作用,并通过细胞内信号网络与细胞核通信,最重要的是通过激活Akt途径。这种激活解释了许多VEGF效应,包括细胞存活、迁移、管形成和促进NO释放。血根碱(Sanguinarine,SA)是从加拿大血根中提取的生物碱,具有抑制基底血管和VEGF诱导的新生血管生长的作用。本文旨在评估SA(300 nM)对猪主动脉内皮细胞系中Akt磷酸化的可能影响。生物碱显著抑制VEGF诱导的Akt增加(P < 0.001),从而表明这种作用方式可能是SA抗血管生成作用的部分原因。
Angiogenesis is the process of vascular growth by sprouting of preexisting vessels. This process impacts significantly on many important disease states including cancer, diabetic retinopathy, and arthritis. Endothelial cells receive multiple information from their environment, which leads them to progress along all stages of new vessel formation. Vascular endothelial growth factor (VEGF), in particular appears to be a master regulator of this process. This molecule interacts with cellular receptors and communicates with cell nucleus through a network of intracellular signaling, most of all by activating Akt pathway. This activation accounts for many of VEGF effects, including cell survival, migration, tube formation, and promotion of NO release. Sanguinarine (SA), an alkaloid isolated from Sanguinaria canadensis, is known for its antiangiogenetic effects by suppressing basal and VEGF-induced new vessel growth. This article was aimed to evaluate the possible effect of SA (300 nM) on Akt phosphorylation in a porcine aortic endothelial cell line. The alkaloid significantly (P < 0.001) inhibited the VEGF-induced Akt increase, thus suggesting that this mode of action could be responsible, at least partially, for the antiangiogenetic effect of SA.