N-hydroxy-7-(2-naphthylthio) heptanomide inhibits retinal and choroidal angiogenesis

Jeong Hun Kim, Jin Hyoung Kim, Meeyeon Oh, Young Suk Yu, Kyu Won Kim, Ho Jeong Kwon

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 labeling-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.

Original languageEnglish
Pages (from-to)513-519
Number of pages7
JournalMolecular Pharmaceutics
Volume6
Issue number2
DOIs
Publication statusPublished - 2009 Apr 6

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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