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

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 compoun...

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Autores: Cerezo López, Ana Belén, Hornedo Ortega, Ruth, García Parrilla, María del Carmen, Troncoso González, Ana María, Labrador, María, Gutiérrez, Andrés
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/89980
Acceso en línea:https://hdl.handle.net/11441/89980
https://doi.org/10.3390/nu11102421
Access Level:acceso abierto
Palabra clave:3-indoleacetic acid
5-hydroxytryptophol
VEGF
angiogenesis
eNOS
hydroxytyrosol
melatonin
serotonin
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spelling Anti-VEGF Signalling Mechanism in HUVECs by Melatonin, Serotonin, Hydroxytyrosol and Other Bioactive CompoundsCerezo López, Ana BelénHornedo Ortega, RuthGarcía Parrilla, María del CarmenTroncoso González, Ana MaríaLabrador, MaríaGutiérrez, Andrés3-indoleacetic acid5-hydroxytryptopholVEGFangiogenesiseNOShydroxytyrosolmelatoninserotoninAngiogenesis 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.MDPINutrición y Bromatología, Toxicología y Medicina Legal2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/89980https://doi.org/10.3390/nu11102421reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésNutrients, 11 (10 , art. 2421), 1-13.http://dx.doi.org/10.3390/nu11102421info:eu-repo/semantics/openAccessoai:idus.us.es:11441/899802026-06-17T12:51:07Z
dc.title.none.fl_str_mv Anti-VEGF Signalling Mechanism in HUVECs by Melatonin, Serotonin, Hydroxytyrosol and Other Bioactive Compounds
title Anti-VEGF Signalling Mechanism in HUVECs by Melatonin, Serotonin, Hydroxytyrosol and Other Bioactive Compounds
spellingShingle Anti-VEGF Signalling Mechanism in HUVECs by Melatonin, Serotonin, Hydroxytyrosol and Other Bioactive Compounds
Cerezo López, Ana Belén
3-indoleacetic acid
5-hydroxytryptophol
VEGF
angiogenesis
eNOS
hydroxytyrosol
melatonin
serotonin
title_short Anti-VEGF Signalling Mechanism in HUVECs by Melatonin, Serotonin, Hydroxytyrosol and Other Bioactive Compounds
title_full Anti-VEGF Signalling Mechanism in HUVECs by Melatonin, Serotonin, Hydroxytyrosol and Other Bioactive Compounds
title_fullStr Anti-VEGF Signalling Mechanism in HUVECs by Melatonin, Serotonin, Hydroxytyrosol and Other Bioactive Compounds
title_full_unstemmed Anti-VEGF Signalling Mechanism in HUVECs by Melatonin, Serotonin, Hydroxytyrosol and Other Bioactive Compounds
title_sort Anti-VEGF Signalling Mechanism in HUVECs by Melatonin, Serotonin, Hydroxytyrosol and Other Bioactive Compounds
dc.creator.none.fl_str_mv Cerezo López, Ana Belén
Hornedo Ortega, Ruth
García Parrilla, María del Carmen
Troncoso González, Ana María
Labrador, María
Gutiérrez, Andrés
author Cerezo López, Ana Belén
author_facet Cerezo López, Ana Belén
Hornedo Ortega, Ruth
García Parrilla, María del Carmen
Troncoso González, Ana María
Labrador, María
Gutiérrez, Andrés
author_role author
author2 Hornedo Ortega, Ruth
García Parrilla, María del Carmen
Troncoso González, Ana María
Labrador, María
Gutiérrez, Andrés
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Nutrición y Bromatología, Toxicología y Medicina Legal
dc.subject.none.fl_str_mv 3-indoleacetic acid
5-hydroxytryptophol
VEGF
angiogenesis
eNOS
hydroxytyrosol
melatonin
serotonin
topic 3-indoleacetic acid
5-hydroxytryptophol
VEGF
angiogenesis
eNOS
hydroxytyrosol
melatonin
serotonin
description 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.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/89980
https://doi.org/10.3390/nu11102421
url https://hdl.handle.net/11441/89980
https://doi.org/10.3390/nu11102421
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Nutrients, 11 (10 , art. 2421), 1-13.
http://dx.doi.org/10.3390/nu11102421
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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