Neamine inhibits prostate cancer growth by suppressing angiogenin-mediated rRNA transcription.
OBJECTIVE
Angiogenin (ANG) undergoes nuclear translocation and stimulates rRNA transcription in both prostate cancer cells and endothelial cells. The purpose of this study is to assess the antitumor activity of neamine, a nontoxic degradation product of neomycin that blocks nuclear translocation of ANG.


METHODS
The anti-prostate cancer activity of neamine was first evaluated in a xenograft animal model. It was then examined in the murine prostate-restricted AKT transgenic mice that develop prostate intraepithelial neoplasia (PIN) owing to AKT transgene overexpression.


RESULTS
Neamine inhibits xenograft growth of PC-3 human prostate cancer cells in athymic mice. It blocks nuclear translocation of ANG and inhibits rRNA transcription, cell proliferation, and angiogenesis. Neamine also prevents AKT-induced PIN formation as well as reverses fully developed PIN in murine prostate-restricted AKT mice, accompanied by a decrease in rRNA synthesis, cell proliferation, and angiogenesis and an increase in prostate epithelial cell apoptosis.


CONCLUSIONS
We confirmed that ANG is a molecular target for cancer drug development and that blocking nuclear translocation of ANG is an effective means to inhibit its activity. Our results also suggested that neamine is a lead compound for further preclinical evaluation.
Ibaragi
Soichiro
S
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Yoshioka
Norie
N
Li
Shuping
S
Hu
Miaofen G
MG
Hirukawa
Saori
S
Sadow
Peter M
PM
Hu
Guo-Fu
GF
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005601:Framycetin / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D012335:RNA, Ribosomal / Q000235:genetics*; D012259:Ribonuclease, Pancreatic / Q000037:antagonists & inhibitors* / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D012335:RNA, Ribosomal; D005601:Framycetin; C488396:neamine; D051057:Proto-Oncogene Proteins c-akt; C046366:angiogenin; D012259:Ribonuclease, Pancreatic