Icariside II from Epimedium koreanum inhibits hypoxia-inducible factor-1α in human osteosarcoma cells
Icariside II from Epimedium koreanum inhibits hypoxia-inducible factor-1α in human osteosarcoma cells
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DOI：
10.1016/j.ejphar.2007.10.010
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发表时间：
2008-01-28
影响因子：
5
通讯作者：
Soh, Yunjo
中科院分区：
文献类型：
--
作者：
Choi, Hwa Jung;Eun, Jae-Soon;Soh, Yunjo
缺氧诱导因子-1（HIF-1）是一种重要的肿瘤选择性治疗靶点。朝鲜淫羊藿经乙酸乙酯、正丁醇、氯仿、正己烷分级分离，凝胶柱层析分离得到淫羊藿苷II。淫羊藿苷II以浓度依赖性方式减弱缺氧诱导的人骨肉瘤（HOS）细胞中HIF-1 α的蛋白水平，可能是通过增强von Hippel-Lindau（VHL）与HIF-1 α之间的相互作用速率。此外，淫羊藿苷II下调HIF诱导的基因的水平，参与血管生成，转移，和葡萄糖代谢，如血管内皮生长因子（VEGF），尿激酶纤溶酶原激活物受体（uPAR），肾上腺髓质素（ADM），基质金属蛋白酶2（MMP 2），醛缩酶A，和烯醇化酶1在HOS细胞。淫羊藿苷Ⅱ还能抑制HOS细胞的迁移率和人脐静脉内皮细胞（HUVECs）的小管形成率。总体而言，这些结果表明，淫羊藿苷H作为治疗候选药物对各种疾病，涉及HIF-1 α过表达的潜在用途。(C)2007 Elsevier B. V.保留所有权利。
Hypoxia-inducible factor-1 (HIF-1) is an important tumor-selective therapeutic target for solid tumors. Icariside II was isolated from Epimedium koreanum through successive fractionation with ethyl acetate, n-butanol, chloroform and hexane, followed by gel column chromatography. Icariside II attenuated the protein level of HIF-1 alpha induced by hypoxia in human osteosarcoma (HOS) cells in a concentration-dependent manner, probably by enhancing the interaction rate between von Hippel-Lindau (VHL) and HIF-1 alpha. Furthermore, Icariside II down-regulated the levels of HIF-inducible genes involved in angiogenesis, metastasis, and glucose metabolism, such as vascular endothelial growth factor (VEGF), urokinase plasminogen activator receptor (uPAR), adrenomedullin (ADM), matrix metalloproteinase 2 (MMP2), aldolase A, and enolase 1 in HOS cells. Icariside II also inhibited the migration rate in HOS cells and tube formation rate in human umbilical vein endothelium cells (HUVECs). Overall, these results suggest the potential use of Icariside H as a therapeutic candidate against various diseases that involve overexpression of HIF-1 alpha. (C) 2007 Elsevier B.V. All rights reserved.