title: Anti-angiogenic and anti-tumor activity of Bavachinin by targeting hypoxia-inducible factor-1α.
abstract: Hypoxia-inducible factor-1 (HIF-1) consists of two subunits, the HIF-1β, which is constitutively expressed, and HIF-1α, which is oxygen-responsive. HIF-1α is over-expressed in response to hypoxia, increasing transcriptional activity linked to tumor progression, angiogenesis, metastasis, and invasion. This study aimed to demonstrate that the natural compound, Bavachinin, has potent anti-angiogenic activity in vitro and in vivo. Bavachinin inhibited increases in HIF-1α activity in human KB carcinoma (HeLa cell derivative) and human HOS osteosarcoma cells under hypoxia in a concentration-dependent manner, probably by enhancing the interaction between von Hippel-Lindau (VHL) and HIF-1α. Furthermore, Bavachinin decreased transcription of genes associated with angiogenesis and energy metabolism that are regulated by HIF-1, such as vascular endothelial growth factors (VEGF), Glut 1 and Hexokinase 2. Bavachinin also inhibited tube formation in human umbilical vein endothelial cells (HUVECs) as well as in vitro migration of KB cells. In vivo studies showed that injecting Bavachinin thrice weekly for four weeks significantly reduced tumor volume and CD31 expression in nude mice with KB xenografts. These data indicate that Bavachinin could be used as a therapeutic agent for inhibiting tumor angiogenesis.
authors: Department of Dental Pharmacology, School of Dentistry, and Brain Korea 21 project, Chonbuk National University, Jeon-Ju, Chonbuk561-756, Republic of Korea.
authors: Manoj
authors: M
authors: Nepal
authors: Hwa Jung
authors: HJ
authors: Choi
authors: Bo-Yun
authors: BY
authors: Choi
authors: Se Lim
authors: SL
authors: Kim
authors: Jae-Ha
authors: JH
authors: Ryu
authors: Do Hee
authors: DH
authors: Kim
authors: Young-Hoon
authors: YH
authors: Lee
authors: Yunjo
authors: Y
authors: Soh
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007624:KB Cells; D051379:Mice; D055806:Microvessels / Q000187:drug effects / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D047309:Flavones
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D005419:Flavonoids; D005947:Glucose; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C497442:HIF1A protein, human; C468752:bavachinin; D047309:Flavones