title: Icariside II from Epimedium koreanum inhibits hypoxia-inducible factor-1alpha in human osteosarcoma cells.
abstract: 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.
authors.affiliation: Department of Dental Pharmacology, School of Dentistry, Chonbuk National University, Jeon-Ju 561-756, Republic of Korea.
authors.forename: Hwa Jung
authors.initials: HJ
authors.lastname: Choi
authors.forename: Jae-Soon
authors.initials: JS
authors.lastname: Eun
authors.forename: Dae Keun
authors.initials: DK
authors.lastname: Kim
authors.forename: Ri Hua
authors.initials: RH
authors.lastname: Li
authors.forename: Tae-Yong
authors.initials: TY
authors.lastname: Shin
authors.forename: Hyunsung
authors.initials: H
authors.lastname: Park
authors.forename: Nam-Pyo
authors.initials: NP
authors.lastname: Cho
authors.forename: Yunjo
authors.initials: Y
authors.lastname: Soh
mesh_terms: D053607:Adrenomedullin / Q000187:drug effects / Q000235:genetics; D001859:Bone Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D034181:Epimedium / Q000737:chemistry*; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D005634:Fructose-Bisphosphate Aldolase / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects / Q000235:genetics; D012516:Osteosarcoma / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000187:drug effects / Q000235:genetics; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000235:genetics; D055293:Receptors, Urokinase Plasminogen Activator; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects / Q000235:genetics; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000187:drug effects / Q000378:metabolism
chemical_list: D005419:Flavonoids; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D042461:Vascular Endothelial Growth Factor A; C060988:baohuoside I; D053607:Adrenomedullin; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D020778:Matrix Metalloproteinase 2; D005634:Fructose-Bisphosphate Aldolase; D010751:Phosphopyruvate Hydratase