title: Preliminary studies on the anti-angiogenic potential of pomegranate fractions in vitro and in vivo.
abstract: We previously showed pomegranate seed oil and fermented juice polyphenols to retard oxidation and prostaglandin synthesis, to inhibit breast cancer cell proliferation and invasion, and to promote breast cancer cell apoptosis. Here we evaluated the anti-angiogenic potential of these materials in several ways. We checked a possible effect on angiogenic regulation by measuring vascular endothelial growth factor (VEGF), interleukin-4 (IL-4) and migration inhibitory factor (MIF) in the conditioned media of estrogen sensitive (MCF-7) or estrogen resistant (MDA-MB-231) human breast cancer cells, or immortalized normal human breast epithelial cells (MCF-10A), grown in the presence or absence of pomegranate seed oil (SESCO) or fermented juice polyphenols (W). VEGF was strongly downregulated in MCF-10A and MCF-7, and MIF upregulated in MDA-MB-231, overall showing significant potential for downregulation of angiogenesis by pomegranate fractions. An anti-proliferative effect on angiogenic cells was shown in human umbilical vein endothelial cell (HUVEC) and in myometrial and amniotic fluid fibroblasts, and inhibition of HUVEC tubule formation demonstrated in an in vitro model employing glass carrier beads. Finally, we showed a significant decrease in new blood vessel formation using the chicken chorioallantoic membrane (CAM) model in vivo. 'In sum, these varied studies employing different models in different laboratories overall demonstrate for the first time an anti-angiogenic potential of pomegranate fractions, suggesting further in vivo and clinical investigations (for updates: info@rimonest.com).
authors.affiliation: Department of Surgery, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Toi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Bando
authors.forename: Cheppail
authors.initials: C
authors.lastname: Ramachandran
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Melnick
authors.forename: Atsushi
authors.initials: A
authors.lastname: Imai
authors.forename: Rose S
authors.initials: RS
authors.lastname: Fife
authors.forename: Raymond Eric
authors.initials: RE
authors.lastname: Carr
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Oikawa
authors.forename: Ephraim Philip
authors.initials: EP
authors.lastname: Lansky
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism; D029561:Lythraceae; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D010936:Plant Extracts; D042461:Vascular Endothelial Growth Factor A; D015847:Interleukin-4