Angiogenesis is target for antineoplastic and chemopreventivetherapies. The natural phytoalexin resveratrolis found in grapes and red wine as cis and trans stereoisomers.trans-Resveratrol shows antiangiogenic activity,but its mechanism of action is not fully elucidated.Recently, trans-resveratrol has been shown to interactwith the B3 integrin subunit, raising the possibility thatinhibition of endothelial AvB3 integrin function may concurto its angiosuppressive activity. To get novel insightsabout the antiangiogenic activity of resveratrol, we comparedcis- and trans-resveratrol stereoisomers for theireffect on the angiogenesis process and endothelial AvB3integrin function. trans-Resveratrol inhibits endothelialcell proliferation and the repair of mechanically woundedendothelial cell monolayers. Also, it prevents endothelialcell sprouting in fibrin gel, collagen gel invasion, andmorphogenesis on Matrigel. In vivo, trans-resveratrolinhibits vascularization of the chick embryo area vasculosaand murine melanoma B16 tumor growth and neovascularization.In all the assays, cis-resveratrol exerts a limited, if any, effect. In keeping with these observations, transresveratrol,but not cis-resveratrol, inhibits AvB3 integrindependentendothelial cell adhesion and the recruitmentof enhanced green fluorescent protein-tagged B3 integrinin focal adhesion contacts. In conclusion, stereoisomeryaffects the antiangiogenic activity of resveratrol, the transisomer being significantly more potent than the cis isoform.The different antiangiogenic potential of resveratrolstereoisomers is related, at least in part, to theirdifferent capacity to affect AvB3 integrin function. Thismay have profound implications for the design of syntheticantiangiogenic/angiopreventive phytoalexin derivatives.

alfa-v-beta-3 Integrin-dependent antiangiogenic activity of resveratrol stereoisomers / M., Belleri; D., Ribatti; M., Savio; L. A., Stivala; Forti, Luca; E., Tanghetti; P., Alessi; D., Coltrini; A., Bugatti; S., Mitola; S., Nicoli; V., Vannini; M., Presta. - In: MOLECULAR CANCER THERAPEUTICS. - ISSN 1535-7163. - STAMPA. - 7:(2008), pp. 3761-3770. [10.1158/1535-7163.MCT-07-2351]

alfa-v-beta-3 Integrin-dependent antiangiogenic activity of resveratrol stereoisomers

FORTI, Luca;
2008

Abstract

Angiogenesis is target for antineoplastic and chemopreventivetherapies. The natural phytoalexin resveratrolis found in grapes and red wine as cis and trans stereoisomers.trans-Resveratrol shows antiangiogenic activity,but its mechanism of action is not fully elucidated.Recently, trans-resveratrol has been shown to interactwith the B3 integrin subunit, raising the possibility thatinhibition of endothelial AvB3 integrin function may concurto its angiosuppressive activity. To get novel insightsabout the antiangiogenic activity of resveratrol, we comparedcis- and trans-resveratrol stereoisomers for theireffect on the angiogenesis process and endothelial AvB3integrin function. trans-Resveratrol inhibits endothelialcell proliferation and the repair of mechanically woundedendothelial cell monolayers. Also, it prevents endothelialcell sprouting in fibrin gel, collagen gel invasion, andmorphogenesis on Matrigel. In vivo, trans-resveratrolinhibits vascularization of the chick embryo area vasculosaand murine melanoma B16 tumor growth and neovascularization.In all the assays, cis-resveratrol exerts a limited, if any, effect. In keeping with these observations, transresveratrol,but not cis-resveratrol, inhibits AvB3 integrindependentendothelial cell adhesion and the recruitmentof enhanced green fluorescent protein-tagged B3 integrinin focal adhesion contacts. In conclusion, stereoisomeryaffects the antiangiogenic activity of resveratrol, the transisomer being significantly more potent than the cis isoform.The different antiangiogenic potential of resveratrolstereoisomers is related, at least in part, to theirdifferent capacity to affect AvB3 integrin function. Thismay have profound implications for the design of syntheticantiangiogenic/angiopreventive phytoalexin derivatives.
7
3761
3770
alfa-v-beta-3 Integrin-dependent antiangiogenic activity of resveratrol stereoisomers / M., Belleri; D., Ribatti; M., Savio; L. A., Stivala; Forti, Luca; E., Tanghetti; P., Alessi; D., Coltrini; A., Bugatti; S., Mitola; S., Nicoli; V., Vannini; M., Presta. - In: MOLECULAR CANCER THERAPEUTICS. - ISSN 1535-7163. - STAMPA. - 7:(2008), pp. 3761-3770. [10.1158/1535-7163.MCT-07-2351]
M., Belleri; D., Ribatti; M., Savio; L. A., Stivala; Forti, Luca; E., Tanghetti; P., Alessi; D., Coltrini; A., Bugatti; S., Mitola; S., Nicoli; V., Vannini; M., Presta
File in questo prodotto:
File Dimensione Formato  
46_paper_MolCancTher.pdf

non disponibili

Tipologia: Post-print dell'autore (bozza post referaggio)
Dimensione 531.97 kB
Formato Adobe PDF
531.97 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/610827
Citazioni
  • ???jsp.display-item.citation.pmc??? 9
  • Scopus 36
  • ???jsp.display-item.citation.isi??? 35
social impact