Icariside II from Epimedium koreanum inhibits hypoxia-inducible factor-1α in human osteosarcoma cells

被引:47
作者
Choi, Hwa Jung [1 ]
Eun, Jae-Soon [2 ]
Kim, Dae Keun [2 ]
Li, Ri Hua [2 ]
Shin, Tae-Yong [2 ]
Park, Hyunsung [3 ]
Cho, Nani-Pyo [4 ,5 ]
Soh, Yunjo [1 ]
机构
[1] Chonbuk Natl Univ, Sch Dent, Dept Dent Pharmacol, Jeon Ju 561756, South Korea
[2] Woosuk Univ, Coll Pharm, Sam Rye 565701, South Korea
[3] Univ Seoul, Dept Life Sci, Seoul 130743, South Korea
[4] Chonbuk Natl Univ, Dept Oral Pathol, Sch Dent, Jeon Ju 561756, South Korea
[5] Chonbuk Natl Univ, Inst Oral Biosci, Jeon Ju 561756, South Korea
关键词
icariside; hypoxia; HIF-1; alpha; HOS; Epimedium koreanum; angiogenesis; metastasis; invasion; VEGF; VHL;
D O I
10.1016/j.ejphar.2007.10.010
中图分类号
R9 [药学];
学科分类号
1007 [药学];
摘要
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.
引用
收藏
页码:58 / 65
页数:8
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