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Correction: Ramírez-Vélez, R.; et al. Validation of Surrogate Anthropometric Indices in Older Adults: What Is the Best Indicator of High Cardiometabolic Risk Factor Clustering? Nutrients 2019, 11, 1701
Open AccessArticle

Anti-VEGF Signalling Mechanism in HUVECs by Melatonin, Serotonin, Hydroxytyrosol and Other Bioactive Compounds

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Departamento de Nutrición y Bromatología, Toxicología y Medicina Legal, Facultad de Farmacia, Universidad de Sevilla. C/Profesor García González 2, 41012 Sevilla, Spain
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MIB, Unité de Recherche Œnologie, EA4577, USC 1366 INRA, ISVV, Université de Bordeaux, 33822 Villenave d’Ornon, Cedex, France
*
Author to whom correspondence should be addressed.
Nutrients 2019, 11(10), 2421; https://doi.org/10.3390/nu11102421
Received: 18 September 2019 / Accepted: 9 October 2019 / Published: 11 October 2019
Angiogenesis drives evolution and destabilisation of atherosclerotic plaques and the growth and expansion of tumour cells. Vascular endothelial growth factor (VEGF) is the main endogenous pro-angiogenic factor in humans. The aim was to provide insight into the anti-VEGF activity of bioactive compounds derived from aromatic amino acids (serotonin, melatonin, 3-indoleacetic acid, 5-hydroxytryptophol and hydroxytyrosol). Experiments involved endothelial cell migration (wound-healing assay), the molecular mechanisms (ELISA assay) and the downstream effects (phospholipase C gamma 1 (PLCγ1), protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS) by Western blot) on human umbilical vein endothelial cells (HUVECs). The data suggest for the first time that hydroxytyrosol interacts with surface components of the endothelial cell membrane (, preventing VEGF from activating its receptor. Serotonin and 5-hydroxytryptophol significantly inhibited HUVEC migration (98% and 50%, respectively) following the same mechanism. Conversely to other bioactive compounds, the anti-angiogenic effect of melatonin, serotonin, 3-indoleacetic acid and 5-hydroxytryptophol is not mediated via PLCγ1. However, hydroxytyrosol inhibits PLCγ1 phosphorylation. Additionally, melatonin and serotonin maintained eNOS phosphorylation and hydroxytyrosol significantly activated eNOS—all via Akt. These data provide new evidence supporting the interest in melatonin, serotonin, 3-indoleacetic acid, 5-hydroxytryptophol and hydroxytyrosol for their further exploitation as anti-VEGF ingredients in food. View Full-Text
Keywords: VEGF; angiogenesis; melatonin; serotonin; 3-indoleacetic acid; 5-hydroxytryptophol; hydroxytyrosol; PLCγ1; Akt; eNOS VEGF; angiogenesis; melatonin; serotonin; 3-indoleacetic acid; 5-hydroxytryptophol; hydroxytyrosol; PLCγ1; Akt; eNOS
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Cerezo, A.B.; Labrador, M.; Gutiérrez, A.; Hornedo-Ortega, R.; Troncoso, A.M.; Garcia-Parrilla, M.C. Anti-VEGF Signalling Mechanism in HUVECs by Melatonin, Serotonin, Hydroxytyrosol and Other Bioactive Compounds. Nutrients 2019, 11, 2421.

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