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N-Hydroxy-7-(2-naphthylthio) Heptanomide Inhibits Retinal and Choroidal Angiogenesis

Cited 14 time in Web of Science Cited 17 time in Scopus
Issue Date
2009-04
Publisher
AMER CHEMICAL SOC
Citation
MOLECULAR PHARMACEUTICS; Vol.6 2; 513-519
Keywords
Anti-angiogenesisretinal neovascularizationN-hydroxy-7-(2-naphthylthio) heptanomidechoroidal neovascularizationhistone deacetylase inhibitor
Abstract
Histone deacetylase (HDAC) is a key enzyme regulating gene expression, including angiogenic cytokine expression. We have previously identified a novel synthetic HDAC inhibitor, known as N-hydroxy-7-(2-naphthylthio) heptanomide (HNHA), with antitumor properties. Here, we investigated the antiangiogenic properties of this small synthetic molecule both in vitro and in vivo. HNHA inhibited nuclear HDAC enzyme activity in human umbilical endothelial cells (HUVECs), an effect accompanied by histone hyperacetylation, p21 upregulation, and cell cycle arrest. HNHA also inhibited vascular endothelial growth factor-induced tube formation and migration of HUVECs, in the absence of any detectable cellular toxicity. Intravitreous injection of HNHA into mice inhibited retinal neovascularization associated with oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV), as determined through fluorescence angiography and vessel counting. Retinas from HNHA-treated animals had a normal histological appearance without any detectable increase in terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeliing-positive cells, showing that this compound did not induce retinal toxicity. These findings indicate that HNHA has direct antiangiogenic effects and may be an effective strategy for inhibiting the pathological retinal and choroidal neovascularization underlying blinding eye diseases.
ISSN
1543-8384
Language
English
URI
https://hdl.handle.net/10371/78028
DOI
https://doi.org/10.1021/mp800178b
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College of Medicine/School of Medicine (의과대학/대학원)Ophthalmology (안과학전공)Journal Papers (저널논문_안과학전공)
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