title: Antiangiogenic potential of grape stem extract through inhibition of vascular endothelial growth factor expression.
abstract: The aim of the present study was to investigate the antiangiogenic potential of a grape stem extract against tube formation by human endothelial cells (EA.hy926). The results showed that at low and non-cytotoxic concentrations (50 and 100 μg/ml) the grape stem extract inhibited tube formation, indicating a possible antiangiogenic activity. Moreover, the results showed that this extract inhibited the expression levels of vascular endothelial growth factor (VEGF), one of the most potent proangiogenic factors, suggesting that the tube formation inhibition by the extract may be exerted through inhibition of VEGF levels. Since it is well established that VEGF prevents apoptosis, the previous finding was further supported by the fact that the grape stem extract induced apoptosis in EA.hy926 cells. Furthermore, it was shown that the extract treatment did not change the levels of the proangiogenic molecules hypoxia inducible factor 1 alpha (HIF-1α) and cyclooxygenase-1 (COX-1). Therefore, these findings indicate that the grape stem extract reduces VEGF levels through mechanisms that may be HIF-1α- and COX-1-independent. The present study is the first showing that grape stem extracts possess antiangiogenic potential. Thus, our findings suggest that since grape stem extracts possess important bioactivities such as antiangiogenic potential, they could be exploited for developing chemopreventive and anticancer agents, while simultaneously protecting the environment through the use of a harmful waste.
authors.affiliation: Department of Biochemistry and Biotechnology, University of Thessaly, Larissa, Greece. stagkos@med.uth.gr.
authors.forename: D
authors.initials: D
authors.lastname: Stagos
authors.forename: A
authors.initials: A
authors.lastname: Apostolou
authors.forename: E
authors.initials: E
authors.lastname: Poulios
authors.forename: E
authors.initials: E
authors.lastname: Kermeliotou
authors.forename: A
authors.initials: A
authors.lastname: Mpatzilioti
authors.forename: K
authors.initials: K
authors.lastname: Kreatsouli
authors.forename: S D
authors.initials: SD
authors.lastname: Koulocheri
authors.forename: S A
authors.initials: SA
authors.lastname: Haroutounian
authors.forename: D
authors.initials: D
authors.lastname: Kouretas
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D051545:Cyclooxygenase 1 / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D018547:Plant Stems; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D027843:Vitis
chemical_list: D020533:Angiogenesis Inhibitors; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010936:Plant Extracts; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human