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
-
- Rats
- Humans
- Stilbenes/chemistry
- Stilbenes/pharmacology*
- Chickens
- Microtubules/drug effects*
- Microtubules/physiology
- Dose-Response Relationship, Drug
- Mice, Inbred BALB C
- Angiogenesis Inhibitors/chemistry
- Angiogenesis Inhibitors/pharmacology*
- Mice
- Male
- Cell Proliferation/drug effects
- Cell Line, Transformed
- Animals
- Rats, Inbred F344
- Zebrafish
- Aorta/cytology
- Aorta/drug effects
- Aorta/physiology
- PubMed
- 15703378 Full text @ Mol. Pharmacol.
Citation
Belleri, M., Ribatti, D., Nicoli, S., Cotelli, F., Forti, L., Vannini, V., Stivala, L.A., and Presta, M. (2005) Antiangiogenic and Vascular-Targeting Activity of the Microtubule-Destabilizing trans-Resveratrol Derivative 3,5,4′-Trimethoxystilbene. Molecular pharmacology. 67(5):1451-1459.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping