title: Neamine inhibits xenografic human tumor growth and angiogenesis in athymic mice.
abstract: OBJECTIVE
  We have previously shown that the aminoglycoside antibiotic neomycin blocks the nuclear translocation of angiogenin and inhibits its angiogenic activity. However, neomycin has not been considered as a favorable drug candidate for clinical development because of its known nephrotoxicity and ototoxicity. The aim of this study is to determine whether neamine, a nontoxic derivative of neomycin, possesses antitumor activity.
  
  
  METHODS
  The effect of neamine on the nuclear translocation of angiogenin was examined by means of immunofluorescence and Western blotting. The antitumor activity of neamine was determined with three different animal models.
  
  
  RESULTS
  Neamine effectively blocked the nuclear translocation of angiogenin in endothelial cells and inhibited angiogenin-induced cell proliferation. It inhibited the establishment of human tumor xenografts in athymic mice in both ectopic and orthotopic tumor models. It also inhibited the progression of established human tumor transplants, whereas the structurally related antibiotic paromomycin had no effect. Immunohistochemical staining showed that both angiogenesis and cancer cell proliferation are inhibited by neamine.
  
  
  CONCLUSIONS
  These results suggest that the nontoxic aminoglycoside antibiotic neamine is an effective inhibitor of nuclear translocation of angiogenin and may serve as an inhibitor for angiogenin-induced angiogenesis and cancer progression.
authors.affiliation: Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Saori
authors.initials: S
authors.lastname: Hirukawa
authors.forename: Karen A
authors.initials: KA
authors.lastname: Olson
authors.forename: Takanori
authors.initials: T
authors.lastname: Tsuji
authors.forename: Guo-fu
authors.initials: GF
authors.lastname: Hu
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000617:Aminoglycosides / Q000627:therapeutic use*; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects; D005601:Framycetin / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism; D012259:Ribonuclease, Pancreatic / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000617:Aminoglycosides; D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D005601:Framycetin; C488396:neamine; C046366:angiogenin; D012259:Ribonuclease, Pancreatic