The small molecule R-(-)-β-O-methylsynephrine binds to nucleoporin 153 kDa and inhibits angiogenesis

Nam Hee Kim, Ngoc Bich Pham, Ronald J. Quinn, Joong Sup Shim, Hee Cho, Sung Min Cho, Sung Wook Park, Jeong Hun Kim, Seung Hyeok Seok, Jong Won Oh, Ho Jeong Kwon

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

R-(-)-β-O-methylsynephrine (OMe-Syn) is a naturally occurring small molecule that was identified in a previous screen as an inhibitor of angiogenesis. In this study, we conducted two animal model experiments to investigate the in vivo antiangiogenic activity of OMe-Syn. OMe-Syn significantly inhibited angiogenesis in a transgenic zebrafish model as well as in a mouse retinopathy model. To elucidate the underlying mechanisms responsible for the antiangiogenic activity of OMe-Syn, we used phage display cloning to isolate potential OMe-Syn binding proteins from human cDNA libraries and identified nucleoporin 153 kDa (NUP153) as a primary binding partner of OMe-Syn. OMe-Syn competitively inhibited mRNA binding to the RNA-binding domain of NUP153. Furthermore, depletion of NUP153 in human cells or zebrafish embryos led to an inhibition of angiogenesis, in a manner similar to that seen in response to OMe-Syn treatment. These data suggest that OMe-Syn is a promising candidate for the development of a novel antiangiogenic agent and that inhibition of NUP153 is possibly responsible for the antiangiogenic activity of OMe-Syn.

Original languageEnglish
Pages (from-to)1088-1099
Number of pages12
JournalInternational Journal of Biological Sciences
Volume11
Issue number9
DOIs
Publication statusPublished - 2015 Jul 16

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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