Neomycin inhibits angiogenin-induced angiogenesis.
A class of angiogenesis inhibitor has emerged from our mechanistic study of the action of angiogenin, a potent angiogenic factor. Neomycin, an aminoglycoside antibiotic, inhibits nuclear translocation of human angiogenin in human endothelial cells, an essential step for angiogenin-induced angiogenesis. The phospholipase C-inhibiting activity of neomycin appears to be involved, because U-73122, another phospholipase C inhibitor, has a similar effect. In contrast, genistein, oxophenylarsine, and staurosporine, inhibitors of tyrosine kinase, phosphotyrosine phosphatase, and protein kinase C, respectively, do not inhibit nuclear translocation of angiogenin. Neomycin inhibits angiogenin-induced proliferation of human endothelial cells in a dose-dependent manner. At 50 microM, neomycin abolishes angiogenin-induced proliferation but does not affect the basal level of proliferation and cell viability. Other aminoglycoside antibiotics, including gentamicin, streptomycin, kanamycin, amikacin, and paromomycin, have no effect on angiogenin-induced cell proliferation. Most importantly, neomycin completely inhibits angiogenin-induced angiogenesis in the chicken chorioallantoic membrane at a dose as low as 20 ng per egg. These results suggest that neomycin and its analogs are a class of agents that may be developed for anti-angiogenin therapy.
Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115, USA. guofu_hu@harvard.edu
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D043925:Angiogenesis Inducing Agents / Q000494:pharmacology* / Q000502:physiology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001693:Biological Transport, Active / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002642:Chick Embryo; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D009355:Neomycin / Q000494:pharmacology*; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology*; D011506:Proteins / Q000494:pharmacology* / Q000502:physiology*; D012343:RNA, Transfer / Q000378:metabolism; D012259:Ribonuclease, Pancreatic; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D043925:Angiogenesis Inducing Agents; D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D011506:Proteins; D012343:RNA, Transfer; C046366:angiogenin; D012259:Ribonuclease, Pancreatic; D010738:Type C Phospholipases; D009355:Neomycin