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Molecular Pharmacology

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Research ArticleORIGINAL ARTICLE

Antiangiogenic and Vascular-Targeting Activity of the Microtubule-Destabilizing trans-Resveratrol Derivative 3,5,4′-Trimethoxystilbene

Mirella Belleri, Domenico Ribatti, Stefania Nicoli, Franco Cotelli, Luca Forti, Vanio Vannini, Lucia Anna Stivala and Marco Presta
Molecular Pharmacology May 2005, 67 (5) 1451-1459; DOI: https://doi.org/10.1124/mol.104.009043
Mirella Belleri
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Domenico Ribatti
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Stefania Nicoli
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Franco Cotelli
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Luca Forti
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Vanio Vannini
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Lucia Anna Stivala
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Marco Presta
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Abstract

Neovascularization plays an important role in neoplasia and angioproliferative diseases. Two major modalities have been developed so far to affect neovascularization: its prevention by antiangiogenic compounds, and immature vessel disruption by vascular-targeting agents. trans-Resveratrol, found in grapes and wine, exerts antioxidant, antineoplastic, and antiangiogenic activities. Here, among various synthetic trans-resveratrol derivatives tested, 3,5,4′-trimethoxystilbene was an antiangiogenic agent 30 to 100 times more potent than parent compound in inhibiting endothelial cell proliferation, sprouting, collagen gel invasion, and morphogenesis (ID50 = 0.3–3.0 μM). In addition, 3,5,4′-trimethoxystilbene acts as a vascular-targeting agent by causing microtubule disassembling and tubulin depolymerization and by impairing the repositioning of the microtubule organization center and the formation of membrane ruffles in migrating endothelial cells. In keeping with a vascular-targeting ability, 3,5,4′-trimethoxystilbene induced apoptosis only in subconfluent endothelial cells and apoptotic regression of immature vessels in the ex vivo rat aorta ring assay. In vivo, 3,5,4′-trimethoxystilbene caused the rapid stasis of blood flow and regression of intersegmental vessels in the trunk of zebrafish embryos. In addition, it inhibited blood vessel growth and caused the disappearance of pre-existing blood vessels in the area vasculosa of the chick embryo. In conclusion, 3,5,4′-trimethoxystilbene associates an antiangiogenic profile to a significant vascular-targeting activity.

  • Received November 10, 2004.
  • Accepted February 9, 2005.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 67 (5)
Molecular Pharmacology
Vol. 67, Issue 5
1 May 2005
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Research ArticleORIGINAL ARTICLE

Antiangiogenic and Vascular-Targeting Activity of the Microtubule-Destabilizing trans-Resveratrol Derivative 3,5,4′-Trimethoxystilbene

Mirella Belleri, Domenico Ribatti, Stefania Nicoli, Franco Cotelli, Luca Forti, Vanio Vannini, Lucia Anna Stivala and Marco Presta
Molecular Pharmacology May 1, 2005, 67 (5) 1451-1459; DOI: https://doi.org/10.1124/mol.104.009043

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Research ArticleORIGINAL ARTICLE

Antiangiogenic and Vascular-Targeting Activity of the Microtubule-Destabilizing trans-Resveratrol Derivative 3,5,4′-Trimethoxystilbene

Mirella Belleri, Domenico Ribatti, Stefania Nicoli, Franco Cotelli, Luca Forti, Vanio Vannini, Lucia Anna Stivala and Marco Presta
Molecular Pharmacology May 1, 2005, 67 (5) 1451-1459; DOI: https://doi.org/10.1124/mol.104.009043
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