Neamine Lnhibits prostate cancer growth by suppressing angiogenin-mediated rRNA transcription

Soichiro Ibaragi, Norie Yoshioka, Shuping Li, Miaofen G. Hu, Saori Hirukawa, Peter M. Sadow, Guo Fu Hu

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Purpose: 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. Experimental Design: 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-3human 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)1981-1988
Number of pages8
JournalClinical Cancer Research
Volume15
Issue number6
DOIs
Publication statusPublished - Mar 15 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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