Icariside II from Epimedium koreanum inhibits hypoxia-inducible factor-1alpha in human osteosarcoma cells.
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.
Choi
Hwa Jung
HJ
Department of Dental Pharmacology, School of Dentistry, Chonbuk National University, Jeon-Ju 561-756, Republic of Korea.
Eun
Jae-Soon
JS
Kim
Dae Keun
DK
Li
Ri Hua
RH
Shin
Tae-Yong
TY
Park
Hyunsung
H
Cho
Nam-Pyo
NP
Soh
Yunjo
Y
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
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