Inhibition of trichostatin A-induced antiangiogenesis by small-interfering RNA for thrombospondin-1

Kang, Jung Hoon; Kim, Soo‐A; Chang, Seo-Yoon; Hong, Susie; Hong, Kyong-Ja

doi:10.1038/emm.2007.45

Cited by 6 publications

(3 citation statements)

References 29 publications

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“…Thus, TSA‐mediated inhibition of Nox4‐ derived H 2 O 2 may lead to decreased expression of eNOS and regulated angiogenesis. In addition, it has been shown that HDAC inhibitors up‐regulate anti‐angigogenic genes such as thrombospondin‐1 and the VEGF competitor semaphorin III . Hence, whether Nox4 signalling is required for up‐regulation of anti‐angiogenic genes by HDAC inhibitors warrants further investigation.…”

Section: Discussionmentioning

confidence: 99%

Trichostatin A, a histone deacetylase inhibitor suppresses NADPH Oxidase 4‐Derived Redox Signalling and Angiogenesis

Hakami

Dusting

Peshavariya

2016

J Cellular Molecular Medi

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Histone deacetylase (HDAC) inhibitors are known to suppress abnormal development of blood vessels. Angiogenic activity in endothelial cells depends upon NADPH oxidase 4 (Nox4)‐dependent redox signalling. We set out to study whether the HDAC inhibitor trichostatin A (TSA) affects Nox4 expression and angiogenesis. Nox4 expression was measured by real time PCR and Western blot analysis in endothelial cells. Hydrogen peroxide (H2O2) was measured by amplex® red assay in endothelial cells. Nox4 was knocked down by Nox4 shRNA. In vitro angiogenic activities such migration and tubulogenesis were assessed using wound healing and Matrigel assays, respectively. In vivo angiogenic activity was assessed using subcutaneous sponge assay in C57Bl/6 and Nox4‐deficient mice. Trichostatin A reduced Nox4 expression in a time‐ and concentration‐dependent manner. Both TSA and Nox4 silencing decreased Nox4 protein and H2O2. Mechanistically, TSA reduced expression of Nox4 via ubiquitination of p300‐ histone acetyltransferase (p300‐HAT). Thus, blocking of the ubiquitination pathway using an inhibitor of ubiquitin‐activating enzyme E1 (PYR‐41) prevented TSA inhibition of Nox4 expression. Trichostatin A also reduced migration and tube formation, and these effects were not observed in Nox4‐deficient endothelial cells. Finally, transforming growth factor beta1 (TGFβ1) enhanced angiogenesis in sponge model in C57BL/6 mice. This response to TGFβ1 was substantially reduced in Nox4‐deficient mice. Similarly intraperitoneal infusion of TSA (1 mg/kg) also suppressed TGFβ1‐induced angiogenesis in C57BL/6 mice. Trichostatin A reduces Nox4 expression and angiogenesis via inhibition of the p300‐HAT‐dependent pathway. This mechanism might be exploited to prevent aberrant angiogenesis in diabetic retinopathy, complicated vascular tumours and malformations.

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Section: Discussionmentioning

confidence: 99%

Trichostatin A, a histone deacetylase inhibitor suppresses NADPH Oxidase 4‐Derived Redox Signalling and Angiogenesis

Hakami

Dusting

Peshavariya

2016

J Cellular Molecular Medi

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“…The mechanism by which valproic acid, a histone deacetylase inhibitor, enhanced the anti-angiogenic and anti-tumor effect of ABT-510 was not examined in the above studies. Other investigators have shown recently that the histone deacetylase inhibitor, trichostatin A, increases TSP-1 expression in cells propagated in vitro (116). This suggests the possibility that the increased effectiveness of ABT-510 administered with valproic acid in the above mouse models of cancer could be due to an increased expression of TSP-1 in the tumor vascular cells induced by valproic acid.…”

Section: Targets For Anti-angiogenic Therapymentioning

confidence: 99%

New molecular targets in angiogenic vessels of glioblastoma tumours

Anderson

McFarland

Gladson

2008

Expert Rev. Mol. Med.

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Anti-angiogenesis approaches have the potential to be particularly effective in the treatment of glioblastoma (GBM) tumors. These tumors exhibit extremely high levels of neovascularization, which may contribute to their extremely aggressive behavior not only by providing oxygenation and nutrition, but also by establishing a leaky vasculature that lacks a blood-brain barrier. This leaky vasculature enables migration of tumor cells as well as the build up of fluid that exacerbates tissue damage due to increased intracranial pressure. Considerable progress has been made in the identification of the pro-and anti-angiogenic factors produced by GBM tumors and, in many cases, the effects of these molecules have been demonstrated in animal models of the disease. The safety and efficacy of some of these approaches have now been demonstrated in clinical trials; however, the ability of tumors to overcome these therapies and to re-establish angiogenesis requires further clinical research regarding potential multi-modality therapies as well as basic research into the regulation of angiogenesis by as yet unidentified factors. Optimization of non-invasive procedures for monitoring of angiogenesis would greatly facilitate such research.

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“…Although little is known about TSP-1-inducible chemical compounds, such a trichostatin A, SQMG is a promising candidate for the treatment of tumor-induced angiogenesis via TSP-1 upregulation. (36) …”

Section: Discussionmentioning

confidence: 99%

Anti‐angiogenesis effect of 3′‐sulfoquinovosyl‐1′‐monoacylglycerol via upregulation of thrombospondin 1

et al. 2012

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We previously reported that 3′-sulfoquinovosyl-1′-monoacylglycerol (SQMG) effectively suppresses the growth of solid tumors, likely via its anti-angiogenic activity. To investigate how SQMG affects angiogenesis, we performed DNA microarray analysis and quantitative real-time polymerase chain reaction. Consequently, upregulation of thrombospondin 1 (TSP-1) in SQMG-treated tumors in vitro and in vivo was confirmed. To address the mechanisms of TSP-1 upregulation by SQMG, we established stable TSP-1-knockdown transformants (TSP1-KT) by short hairpin RNA induction and performed reporter assay and in vivo assessment of anti-tumor assay. On the reporter assay, transcriptional upregulation of TSP-1 in TSP1-KT could not be induced by SQMG, thus suggesting that TSP-1 upregulation by SQMG occurred via TSP-1 molecule. In addition, growth of TSP1-KT xenografted tumors in vivo was not inhibited by SQMG, thus suggesting that antiangiogenesis via TSP-1 upregulation induced by SQMG did not occur, as the SQMG target molecule TSP-1 was knocked down in TSP1-KT transformants. These data provide that SQMG is a promising candidate for the treatment of tumor-induced angiogenesis via TSP-1 upregulation. (Cancer Sci 2012; 103: 1546-1552

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Inhibition of trichostatin A-induced antiangiogenesis by small-interfering RNA for thrombospondin-1

Cited by 6 publications

References 29 publications

Trichostatin A, a histone deacetylase inhibitor suppresses NADPH Oxidase 4‐Derived Redox Signalling and Angiogenesis

Trichostatin A, a histone deacetylase inhibitor suppresses NADPH Oxidase 4‐Derived Redox Signalling and Angiogenesis

New molecular targets in angiogenic vessels of glioblastoma tumours

Anti‐angiogenesis effect of 3′‐sulfoquinovosyl‐1′‐monoacylglycerol via upregulation of thrombospondin 1

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