@article{10902/21133,
year = {2020},
url = {http://hdl.handle.net/10902/21133},
abstract = {Chemotherapeutics are sometimes administered with drugs, like antiangiogenic compounds, to
increase their effectiveness. Melatonin exerts antitumoral actions through antiangiogenic actions.
We studied if melatonin regulates the response of HUVECs to chemotherapeutics (docetaxel and
vinorelbine). The inhibition that these agents exert on some of the processes involved in angiogenesis,
such as, cell proliferation, migratory capacity or vessel formation, was enhanced by melatonin.
Regarding to estrogen biosynthesis, melatonin impeded the negative effect of vinorelbine, by
decreasing the activity and expression of aromatase and sulfatase. Docetaxel and vinorelbine increased
the expression of VEGF-A, VEGF-B, VEGF-C, VEGFR-1, VEGFR-3, ANG1 and/or ANG-2 and melatonin
inhibited these actions. Besides, melatonin prevented the positive actions that docetaxel exerts on
the expression of other factors related to angiogenesis like JAG1, ANPEP, IGF-1, CXCL6, AKT1, ERK1,
ERK2, MMP14 and NOS3 and neutralized the stimulating actions of vinorelbine on the expression of
FIGF, FGFR3, CXCL6, CCL2, ERK1, ERK2, AKT1, NOS3 and MMP14. In CAM assay melatonin inhibited
new vascularization in combination with chemotherapeutics. Melatonin further enhanced the
chemotherapeutics-induced inhibition of p-AKT and p-ERK and neutralized the chemotherapeuticscaused
stimulatory effect on HUVECs permeability by modifying the distribution of VE cadherin. Our
results confirm that melatonin blocks proangiogenic and potentiates antiangiogenic effects induced by
docetaxel and vinorelbine enhancing their antitumor effectiveness.},
organization = {This work was supported by grants from the Spanish Economy and Competitiveness Ministry (SAF2016-77103-P) and from Instituto de Investigación Sanitaria Valdecilla (IDIVAL) (APG/12).},
publisher = {Nature Publishing Group},
publisher = {Scientific Reports volume 10, Article number: 4790 (2020)},
title = {Usefulness of melatonin as complementary to chemotherapeutic agents at different stages of the angiogenic process},
author = {González- González, Alicia and Rueda Revilla, Noemí and Alonso González, Carolina and Menéndez Menéndez, Javier and Martínez Campa, Carlos Manuel and Mitola, Stefania and Cos Corral, Samuel},
}