title: Dienogest, a synthetic steroid, suppresses both embryonic and tumor-cell-induced angiogenesis.
abstract: Orally administered dienogest (17alpha-cyanomethyl-17beta-hydroxy-estra-4,9-diene-3-one) is efficacious against human hormone-dependent cancer xenografts in severely immunodeficient mice and in rats with experimental endometriosis, but its mechanisms of action remain unclear. We assessed the effect of dienogest on angiogenesis, because these two diseases that are sensitive to dienogest are known to be angiogenesis-dependent. Topical dienogest treatment dose-dependently inhibited embryonic angiogenesis, the ID(50) value being 6.4 nmol/egg. Oral administration of dienogest (1 mg kg(-1) day(-1)) for 5 consecutive days significantly suppressed angiogenesis induced by S-180 mouse tumor cells in the mouse dorsal air sac assay. In vitro experiments showed that dienogest at concentrations up to 10 microM had little or no effect on the proliferation of plasminogen activator activity or formation of tube-like structures by microvascular endothelial cells. These results suggest that dienogest is a new, orally active antagonist of angiogenesis, and that its anti-angiogenic action may be involved in its therapeutic effects on cancer xenografts and endometriosis that we observed previously.
authors.affiliation: Department of Molecular Oncology, The Tokyo Metropolitan Institute of Medical Science (Rinshoken), Tokyo Metropolitan Organization for Medical Research, 3-18-22 Honkomagome Bunkyo-ku, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
authors.forename: Y
authors.initials: Y
authors.lastname: Katsuki
authors.forename: Y
authors.initials: Y
authors.lastname: Shibutani
authors.forename: T
authors.initials: T
authors.lastname: Oikawa
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002823:Chorion / Q000187:drug effects; D003864:Depression, Chemical; D004622:Embryo, Mammalian / Q000098:blood supply*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D008833:Microcirculation / Q000187:drug effects; D009277:Nandrolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009389:Neovascularization, Pathologic / Q000473:pathology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010960:Plasminogen Activators / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D020533:Angiogenesis Inhibitors; D018931:Antineoplastic Agents, Hormonal; C023635:dienogest; D009277:Nandrolone; D010960:Plasminogen Activators