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

doi:10.1016/j.bbrc.2011.08.055

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 journal › Article › peer-review

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 language	English
Pages (from-to)	189-193
Number of pages	5
Journal	Biochemical and Biophysical Research Communications
Volume	413
Issue number	2
DOIs	https://doi.org/10.1016/j.bbrc.2011.08.055
Publication status	Published - 2011 Sept 23

Bibliographical note

Funding Information:
This study partly supported by grants from the National Research Foundation of Korea funded by the Korean Government (MEST; 2009-0092964 , 2010-0017984 , F01-2009-000-10183-0 ), the Translational Research Center for Protein Function Control, KRF ( 2009-0083522 ), the Center for Food and Drug Materials of Agriculture Science & Technology Development ( 2011-8-1178 ) Rural Development Administration, National R&D Program, Ministry of Health & Welfare , and the Brain Korea 21 project, Republic of Korea.

All Science Journal Classification (ASJC) codes

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2011.08.055

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title = "The sphingosine-1-phosphate derivative NHOBTD inhibits angiogenesis both in vitro and in vivo",

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.",

author = "Kim, {Beom Seok} and Hyomi Park and Ko, {Seung Hwan} and Lee, {Won Koo} and Kwon, {Ho Jeong}",

note = "Funding Information: This study partly supported by grants from the National Research Foundation of Korea funded by the Korean Government (MEST; 2009-0092964 , 2010-0017984 , F01-2009-000-10183-0 ), the Translational Research Center for Protein Function Control, KRF ( 2009-0083522 ), the Center for Food and Drug Materials of Agriculture Science & Technology Development ( 2011-8-1178 ) Rural Development Administration, National R&D Program, Ministry of Health & Welfare , and the Brain Korea 21 project, Republic of Korea.",

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AU - Lee, Won Koo

AU - Kwon, Ho Jeong

N1 - Funding Information: This study partly supported by grants from the National Research Foundation of Korea funded by the Korean Government (MEST; 2009-0092964 , 2010-0017984 , F01-2009-000-10183-0 ), the Translational Research Center for Protein Function Control, KRF ( 2009-0083522 ), the Center for Food and Drug Materials of Agriculture Science & Technology Development ( 2011-8-1178 ) Rural Development Administration, National R&D Program, Ministry of Health & Welfare , and the Brain Korea 21 project, Republic of Korea.

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N2 - 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.

AB - 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.

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

Abstract

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