baohuoside-i and Bone-Neoplasms

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-1alpha 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-1alpha. 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 II as a therapeutic candidate against various diseases that involve overexpression of HIF-1alpha.

Topics: Adrenomedullin; Bone Neoplasms; Cell Line, Tumor; Dose-Response Relationship, Drug; Down-Regulation; Epimedium; Flavonoids; Fructose-Bisphosphate Aldolase; Gene Expression Regulation, Neoplastic; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Matrix Metalloproteinase 2; Osteosarcoma; Phosphopyruvate Hydratase; Receptors, Cell Surface; Receptors, Urokinase Plasminogen Activator; Vascular Endothelial Growth Factor A; Von Hippel-Lindau Tumor Suppressor Protein