title: Antiangiogenic activity of herboxidiene via downregulation of vascular endothelial growth factor receptor-2 and hypoxia-inducible factor-1α.
abstract: Antiangiogenesis is now thought of as one of the most important approaches for anticancer therapy. In this study, we determined the antiangiogenic property of herboxidiene, a polyketide natural product. Herboxidiene effectively inhibited the proliferation of human umbilical vein endothelial cells (HUVECs) at concentrations not exhibiting cytotoxicity. Furthermore, the natural product significantly suppressed vascular endothelial growth factor-induced invasion and tube formation in HUVECs as well as neovascularization of the chorioallantoic membrane in developing chick embryos. We also identified an association between the antiangiogenic activity of herboxidiene and the downregulation of both the phosphorylation of VEGF receptor 2 (KDR/Flk-1) and the expression of hypoxia-inducible factor-1α at the transcriptional level. These results suggest that herboxidiene functions as a potential antiangiogenic agent and may be applicable for anticancer therapy by targeting tumor angiogenesis.
authors.affiliation: Department of BT-Convergent Pharmaceutical Engineering, Sun Moon University, 70, Sunmoon-ro 221, Tangjeong-myeon, Asan-si, Chungnam, 336-708, Republic of Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Jung
authors.affiliation: Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-749, Republic of Korea.
authors.forename: Yonghyo
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of BT-Convergent Pharmaceutical Engineering, Sun Moon University, 70, Sunmoon-ro 221, Tangjeong-myeon, Asan-si, Chungnam, 336-708, Republic of Korea.
authors.forename: Ju Yong
authors.initials: JY
authors.lastname: Shin
authors.affiliation: Department of BT-Convergent Pharmaceutical Engineering, Sun Moon University, 70, Sunmoon-ro 221, Tangjeong-myeon, Asan-si, Chungnam, 336-708, Republic of Korea.
authors.forename: Jae Kyung
authors.initials: JK
authors.lastname: Sohng
authors.affiliation: Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-749, Republic of Korea. kwonhj@yonsei.ac.kr.|Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, 120-752, Republic of Korea. kwonhj@yonsei.ac.kr.
authors.forename: Ho Jeong
authors.initials: HJ
authors.lastname: Kwon
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects* / Q000502:physiology; D005233:Fatty Alcohols / Q000494:pharmacology*; D056945:Hep G2 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011714:Pyrans / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D005233:Fatty Alcohols; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011714:Pyrans; C076087:herboxidiene; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Antiangiogenesis; HIF-1α; Herboxidiene; VEGFR2