Next Article in Journal
Genetic Variations Associated with Vitamin A Status and Vitamin A Bioavailability
Next Article in Special Issue
Dietary Broccoli Alters Rat Cecal Microbiota to Improve Glucoraphanin Hydrolysis to Bioactive Isothiocyanates
Previous Article in Journal
Does the Dietary Pattern of Shanghai Residents  Change across Seasons and Area of Residence:  Assessing Dietary Quality Using the Chinese Diet  Balance Index (DBI)
Previous Article in Special Issue
Effects of Acute Blueberry Flavonoids on Mood in Children and Young Adults
Article Menu
Issue 3 (March) cover image

Export Article

Open AccessArticle
Nutrients 2017, 9(3), 249; doi:10.3390/nu9030249

Inhibition of VEGF-Induced VEGFR-2 Activation and HUVEC Migration by Melatonin and Other Bioactive Indolic Compounds

Departamento de Nutrición y Bromatología, Toxicología y Medicina Legal, Facultad de Farmacia, Universidad de Sevilla, C/P. García González s/n, 41012 Sevilla, Spain
*
Author to whom correspondence should be addressed.
Received: 25 November 2016 / Revised: 1 March 2017 / Accepted: 3 March 2017 / Published: 8 March 2017
View Full-Text   |   Download PDF [2440 KB, uploaded 8 March 2017]   |  

Abstract

Excessive concentrations of vascular endothelial growth factor (VEGF) trigger angiogenesis, which causes complications such as the destabilization of atherosclerotic plaques and increased growth of tumors. This work focuses on the determination of the inhibitory activity of melatonin and other indolic related compounds on VEGF-induced VEGF receptor-2 (VEGFR-2) activation and an approximation to the molecular mechanism underlying the inhibition. Quantification of phosphorylated VEGFR-2 was measured by ELISA. Migration wound-healing assay was used to determine cell migration of human umbilical vein endothelial cells (HUVECs). This is the first time that melatonin, 3-indolacetic acid, 5-hydroxytryptophol, and serotonin are proved to significantly inhibit VEGF-induced VEGFR-2 activation in human umbilical vein endothelial cells and subsequent angiogenesis. 3-Indolacetic acid showed the highest inhibitory effect (IC50 value of 0.9704 mM), followed by 5-hydroxytryptophol (35% of inhibition at 0.1 mM), melatonin (30% of inhibition at 1 mM), and serotonin (24% of inhibition at 1 mM). An approximation to the molecular mechanism of the inhibition has been proposed, suggesting that indolic compounds might interact with the cell surface components of the endothelial membrane in a way that prevents VEGF from activating the receptor. Additionally, wound-healing assay revealed that exposure of HUVECs to melatonin and 3-indolacetic acid in the presence of VEGF significantly inhibited cell migration by 87% and 99%, respectively, after 24 h. These data demonstrate that melatonin, 3-indolacetic acid, 5-hydroxytryptophol, and serotonin would be good molecules for future exploitation as anti-VEGF signaling agents. View Full-Text
Keywords: melatonin; serotonin; 3-indolacetic acid; 5-hydroxytryptophol; VEGF; VEGFR-2; anti-angiogenic; HUVEC; migration melatonin; serotonin; 3-indolacetic acid; 5-hydroxytryptophol; VEGF; VEGFR-2; anti-angiogenic; HUVEC; migration
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Cerezo, A.B.; Hornedo-Ortega, R.; Álvarez-Fernández, M.A.; Troncoso, A.M.; García-Parrilla, M.C. Inhibition of VEGF-Induced VEGFR-2 Activation and HUVEC Migration by Melatonin and Other Bioactive Indolic Compounds. Nutrients 2017, 9, 249.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Nutrients EISSN 2072-6643 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top