title: Suppression of tumor-induced angiogenesis by Brazilian propolis: major component artepillin C inhibits in vitro tube formation and endothelial cell proliferation.
abstract: Propolis, a resinous substance collected by honeybees from various plant sources, possesses various physiological activities such as antitumor effects. We have previously shown that propolis of Brazilian origin was composed mainly of artepillin C and that its constituents were quite different from those of propolis of European origin. In this report, we examined an antiangiogenic effects of Brazilian propolis and investigated whether artepillin C was responsible for such effects. In an in vivo angiogenesis assay using ICR mice, we found that the ethanol extract of Brazilian propolis (EEBP) significantly reduced the number of newly formed vessels. EEBP also showed antiangiogenic effects in an in vitro tube formation assay. When compared with other constituents of EEBP, only artepillin C was found to significantly inhibit the tube formation of HUVECs in a concentration-dependent manner (3.13-50microg/ml). In addition, artepillin C significantly suppressed the proliferation of HUVECs in a concentration-dependent manner (3.13-50microg/ml). Furthermore, artepillin C significantly reduced the number of newly formed vessels in an in vivo angiogenesis assay. Judging from its antiangiogenic activity in vitro and in vivo, we concluded that artepillin C at least in part is responsible for the antiangiogenic activity of EEBP in vivo. Artepillin C may prove useful in the development of agents and foods with therapeutic or preventive activity against tumor angiogenesis.
authors.affiliation: Laboratory of Functional Food Science and COE Program in the 21st Century, School of Food and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: Mok-Ryeon
authors.initials: MR
authors.lastname: Ahn
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kunimasa
authors.forename: Toshiro
authors.initials: T
authors.lastname: Ohta
authors.forename: Shigenori
authors.initials: S
authors.lastname: Kumazawa
authors.forename: Miya
authors.initials: M
authors.lastname: Kamihira
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Kaji
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Uto
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hori
authors.forename: Hideko
authors.initials: H
authors.lastname: Nagasawa
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakayama
mesh_terms: D000818:Animals; D001938:Brazil; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000098:blood supply*; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D010666:Phenylpropionates / Q000494:pharmacology*; D011429:Propolis / Q000737:chemistry*
chemical_list: D010666:Phenylpropionates; C102259:artepillin C; D011429:Propolis