PUBLICATION

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

Authors
Belleri, M., Ribatti, D., Nicoli, S., Cotelli, F., Forti, L., Vannini, V., Stivala, L.A., and Presta, M.
ID
ZDB-PUB-050211-6
Date
2005
Source
Molecular pharmacology   67(5): 1451-1459 (Journal)
Registered Authors
Cotelli, Franco
Keywords
FGF, Immunocytochemistry, Cytoskeletal targets, Angiogenesis
MeSH Terms
  • Angiogenesis Inhibitors/chemistry
  • Angiogenesis Inhibitors/pharmacology*
  • Animals
  • Aorta/cytology
  • Aorta/drug effects
  • Aorta/physiology
  • Cell Line, Transformed
  • Cell Proliferation/drug effects
  • Chickens
  • Dose-Response Relationship, Drug
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Microtubules/drug effects*
  • Microtubules/physiology
  • Rats
  • Rats, Inbred F344
  • Stilbenes/chemistry
  • Stilbenes/pharmacology*
  • Zebrafish
PubMed
15703378 Full text @ Mol. Pharmacol.
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 or 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 30-100 times more potent than parent compound in inhibiting endothelial cell proliferation, sprouting, collagen gel invasion, and morphogenesis (ID50 = 0.3-3.0 microM). Also, 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. Also, 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.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping