αvβ3 Integrin-dependent antiangiogenic activity of resveratrol stereoisomers

Belleri, Mirella; Ribatti, Doménico; Savio, Monica; Stivala, Lucia Anna; Forti, Luca; Tanghetti, Elena; Alessi, Patrizia; Coltrini, Daniela; Bugatti, Antonella; Mitola, Stefania; Nicoli, Stefania; Vannini, Vanio; Presta, Marco

doi:10.1158/1535-7163.mct-07-2351

Cited by 43 publications

(42 citation statements)

References 37 publications

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“…This effect is inhibited by t-RESV, but not by c-RESV, and similar results are observed in postcapillary venules. Although a number of in vitro studies have revealed quantitative differences in the activity of the two forms, with the cis isomer appearing to be less active than its trans isomer (34)(35)(36), to our knowledge this is the first report to show that t-RESV inhibits the leukocyte-endothelial cell interactions induced by Ang-II in vivo, whereas c-RESV does not. Based on this finding, t-RESV was used in all subsequent experiments to elucidate and characterize the cardiovascular effects of RESV.…”

Section: Discussionmentioning

confidence: 71%

Trans- but Not Cis-Resveratrol Impairs Angiotensin-II–Mediated Vascular Inflammation through Inhibition of NF-κB Activation and Peroxisome Proliferator-Activated Receptor-γ Upregulation

Rius¹,

Abu-Taha²,

Hermenegildo

et al. 2010

The Journal of Immunology

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Angiotensin II (Ang-II) displays inflammatory activity and is implicated in several cardiovascular disorders. This study evaluates the effect of cis- and trans (t)-resveratrol (RESV) in two in vivo models of vascular inflammation and identifies the cardioprotective mechanisms that underlie them. In vivo, Ang-II–induced arteriolar leukocyte adhesion was inhibited by 71% by t-RESV (2.1 mg/kg, i.v.), but was not affected by cis-RESV. Because estrogens influence the rennin-angiotensin system, chronic treatment with t-RESV (15 mg/kg/day, orally) inhibited ovariectomy-induced arteriolar leukocyte adhesion by 81%, partly through a reduction of cell adhesion molecule (CAM) expression and circulating levels of cytokine-induced neutrophil chemoattractant, MCP-1, and MIP-1α. In an in vitro flow chamber system, t-RESV (1–10 μM) undermined the adhesion of human leukocytes under physiological flow to Ang-II–activated human endothelial cells. These effects were accompanied by reductions in monocyte and endothelial CAM expression, chemokine release, phosphorylation of p38 MAPK, and phosphorylation of the p65 subunit of NF-κB. Interestingly, t-RESV increased the expression of peroxisome proliferator-activated receptor-γ in human endothelial and mononuclear cells. These results demonstrate for the first time that the in vivo anti-inflammatory activity of RESV is produced by its t-RESV, which possibly interferes with signaling pathways that cause the upregulation of CAMs and chemokine release. Upregulation of proliferator-activated receptor-γ also appears to be involved in the cardioprotective effects of t-RESV. In this way, chronic administration of t-RESV may reduce the systemic inflammatory response associated with the activation of the rennin-angiotensin system, thereby decreasing the risk of further cardiovascular disease.

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Section: Discussionmentioning

confidence: 71%

Trans- but Not Cis-Resveratrol Impairs Angiotensin-II–Mediated Vascular Inflammation through Inhibition of NF-κB Activation and Peroxisome Proliferator-Activated Receptor-γ Upregulation

Rius¹,

Abu-Taha²,

Hermenegildo

et al. 2010

The Journal of Immunology

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“…However, it should be noticed that the synthetic resveratrol derivative, 3,5,4Ј-trimethoxystilbene, has been shown to cause morphological changes and development arrest of zebrafish embryos. 21) Together, these results indicate that polyphenolic compounds have different effects on embryonic development and survival of zebrafish. Abnormal development or death of curcumin treated zebrafish embryos may result from the deregulation of the functions of multiple genes.…”

Section: Dosage-dependent Toxic Effects Of Curcumin Exposurementioning

confidence: 87%

Curcumin Affects Development of Zebrafish Embryo

Lin

et al. 2007

Biological & Pharmaceutical Bulletin

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Curcumin (diferuloylmethane) is a dietary polyphenol derived from the rhizomes of turmeric (Curcuma longa). For a long time, curcumin has been applied as an anti-inflammatory, 1) anti-oxidative, 2-4) and anti-carcinogenic 5) compound. The multiple therapeutic effects of curcumin result from its ability to modulate enzyme activities and gene expression. For example, curcumin has been shown to down-regulate the activities of several transcription factors, including NF-kappa B, AP-1, and Egr-1, as well as growth factor receptors such as EGFR and HER2. 6) Curcumin also inhibits the activities of COX2, LOX, iNOS, MMP-9, c-Jun N-terminal kinase, protein tyrosine kinases, and protein serine/threonine kinases. 6) Curcumin has been shown to repress expression of oncogenes such as c-fos, c-jun and c-myc, and suppress proliferation of tumour cells. [7][8][9] Finally, recent studies have demonstrated that curcumin can inhibit p300/CBP histone acetyltransferase activity both in vivo and in vitro. 10,11) p300/CBP transfers the acetyl group from an acetyl-CoA to conserved lysine residues in the histones, consequently, leading to transcription activity.12) Therefore, curcumin may modulate gene expression through inhibition of p300/CBP activities.Although the effects of curcumin on enzyme activities and gene expression have been studied in detail, only a few reports described its toxicity to embryos. The studies using rats as animal models have shown that orally administered curcumin has no toxic effects on fertility or pregnancy in the fed rats, and no malformations were observed in their offspring.13) In this report, we used zebrafish (Danio rerio) as model organisms to investigate the developmental toxicity of curcumin. Advantages of using zebrafish as model organisms include their small size (2-4 cm long), ease of breeding in the laboratory, light-induced fertilization, and sensitivity to environmental changes. Our results indicated that, unlike in rats, curcumin had embryotoxic and teratogenic effects on zebrafish embryos in a mM region. MATERIALS AND METHODS Collecting Fertilized Zebrafish EggsAdult zebrafish purchased from a local fish store were maintained in a laboratory under 28Ϯ1°C and a 14 h day/10 h night photoperiod.Fertilized eggs were collected within 30 min after natural mating, washed with sterile water, and placed in petri dishes.Curcumin Treatment and Embryos Observances Curcumin was purchased from Sigma Chemical (St. Louis, MO, U.S.A.), and dissolved in dimethyl sulfoxide (DMSO) to make a 25 mM stock solution. For embryo exposures, fertilized eggs were placed in 6-well petri dishes with ten embryos per well in 10 ml sterile water. Next, 30 ml of seriously diluted curcumin stock solutions was added to get final concentrations of 5, 7.5, 10, 12.5, and 15 mM. Thirty embryos were used for each of four replicates. The embryotoxic and teratogenic effects of resveratrol, quercetin, and rutin were also investigated in this study. Resveratrol, quercetin, and rutin were all purchased from Sigma Chemical (St. Louis, MO...

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“…One of the proposed cellular mechanisms of antiangiogenic activity of resveratrol is related to the reported binding and inhibition of integrin V 3 by resveratrol 31) , which results in the inhibition of sprouting and tube formation 32) . In the present study, we demonstrated that an additional mechanism involving the ROCK pathway can contribute to the inhibitory activity of resveratrol on endothelial cell migration.…”

Section: Discussionmentioning

confidence: 99%