The sphingosine-1-phosphate derivative NHOBTD inhibits angiogenesis both in vitro and in vivo

Beom Seok Kim, Hyomi Park, Seung Hwan Ko, Won Koo Lee, Ho Jeong Kwon

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Sphingosine-1-phosphate (S1P) plays an important role in angiogenesis by stimulating DNA synthesis, chemotactic motility, and early blood vessel formation. Accordingly, the S1P signaling pathway is an attractive target for novel anti-angiogenic therapeutics. Here, we describe a small synthetic derivative of S1P that acts as an anti-angiogenic agent. We found that the S1P derivative NHOBTD [. N-((2. S,3. R)-3-hydroxy-1-morpholino-4-(3-octylphenyl)butan-2-yl)tetradecanamide] suppressed S1P-induced invasion and tube formation by human umbilical vein endothelial cells. NHOBTD also suppressed S1P signaling, as seen by destabilization of hypoxia inducible factor-1 alpha (HIF-1α) and secretion of VEGF, a transcriptional target of HIF-1α. Moreover, NHOBTD profoundly blocked endogenous neovascularization of the chick embryo chorioallantoic membrane, without rupturing any existing vessels. Together, these results demonstrate that NHOBTD is a new anti-angiogenic molecule that is capable of perturbing S1P signaling, and provides the basis for developing new anti-angiogenic drugs.

Original languageEnglish
Pages (from-to)189-193
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume413
Issue number2
DOIs
Publication statusPublished - 2011 Sep 23

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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