Neamine inhibits xenografic human tumor growth and angiogenesis in athymic mice.
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.
Hirukawa
Saori
S
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Olson
Karen A
KA
Tsuji
Takanori
T
Hu
Guo-fu
GF
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
D000617:Aminoglycosides; D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D005601:Framycetin; C488396:neamine; C046366:angiogenin; D012259:Ribonuclease, Pancreatic