Development of in vitro and in vivo tools to evaluate the antiangiogenic potential of melatonin to neutralize the angiogenic effects of VEGF and breast cancer cells: CAM assay and 3D endothelial cell spheroids

Melatonin is a molecule with different antitumor actions in breast cancer and has been described as an inhibitor of vascular endothelial growth factor (VEGF). Despite the recognition of the key role exerted by VEGF in tumor angiogenesis, limitations arise when developing models to test new antiangio...

Full description

Bibliographic Details
Main Authors: Aurora Laborda-Illanes, Lidia Sánchez-Alcoholado, Daniel Castellano-Castillo, Soukaina Boutriq, Isaac Plaza-Andrades, Lucía Aranega-Martín, Jesús Peralta-Linero, Emilio Alba, Alicia González-González, María Isabel Queipo-Ortuño
Format: Article
Language:English
Published: Elsevier 2023-01-01
Series:Biomedicine & Pharmacotherapy
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0753332222014305
_version_ 1811187726221836288
author Aurora Laborda-Illanes
Lidia Sánchez-Alcoholado
Daniel Castellano-Castillo
Soukaina Boutriq
Isaac Plaza-Andrades
Lucía Aranega-Martín
Jesús Peralta-Linero
Emilio Alba
Alicia González-González
María Isabel Queipo-Ortuño
author_facet Aurora Laborda-Illanes
Lidia Sánchez-Alcoholado
Daniel Castellano-Castillo
Soukaina Boutriq
Isaac Plaza-Andrades
Lucía Aranega-Martín
Jesús Peralta-Linero
Emilio Alba
Alicia González-González
María Isabel Queipo-Ortuño
author_sort Aurora Laborda-Illanes
collection DOAJ
description Melatonin is a molecule with different antitumor actions in breast cancer and has been described as an inhibitor of vascular endothelial growth factor (VEGF). Despite the recognition of the key role exerted by VEGF in tumor angiogenesis, limitations arise when developing models to test new antiangiogenic molecules. Thus, the aim of this study was to develop rapid, economic, high capacity and easy handling angiogenesis assays to test the antiangiogenic effects of melatonin and demonstrate its most effective dose to neutralize and interfere with the angiogenic sprouting effect induced by VEGF and MCF-7. To perform this, 3D endothelial cell (HUVEC) spheroids and a chicken embryo chorioallantoic membrane (CAM) assay were used. The results showed that VEGF and MCF-7 were able to stimulate the sprouting of the new vessels in 3D endothelial spheroids and the CAM assay, and that melatonin had an inhibitory effect on angiogenesis. Specifically, as the 1 mM pharmacological dose was the only effective dose able to inhibit the formation of ramifications around the alginate in the CAM assay model, this inhibition was shown to occur in a dose-dependent manner. Taken together, these techniques represent novel tools for the development of antiangiogenic molecules such as melatonin, with possible implications for the therapy of breast cancer.
first_indexed 2024-04-11T14:08:20Z
format Article
id doaj.art-9ec277ca0d724e5bbd14f713ad064c34
institution Directory Open Access Journal
issn 0753-3322
language English
last_indexed 2024-04-11T14:08:20Z
publishDate 2023-01-01
publisher Elsevier
record_format Article
series Biomedicine & Pharmacotherapy
spelling doaj.art-9ec277ca0d724e5bbd14f713ad064c342022-12-22T04:19:49ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-01-01157114041Development of in vitro and in vivo tools to evaluate the antiangiogenic potential of melatonin to neutralize the angiogenic effects of VEGF and breast cancer cells: CAM assay and 3D endothelial cell spheroidsAurora Laborda-Illanes0Lidia Sánchez-Alcoholado1Daniel Castellano-Castillo2Soukaina Boutriq3Isaac Plaza-Andrades4Lucía Aranega-Martín5Jesús Peralta-Linero6Emilio Alba7Alicia González-González8María Isabel Queipo-Ortuño9Intercenter Medical Oncology Clinical Management Unit, Regional and Virgen de la Victoria University Hospitals, Málaga Biomedical Research Institute (IBIMA)-CIMES-UMA, 29010 Málaga, SpainIntercenter Medical Oncology Clinical Management Unit, Regional and Virgen de la Victoria University Hospitals, Málaga Biomedical Research Institute (IBIMA)-CIMES-UMA, 29010 Málaga, SpainIntercenter Medical Oncology Clinical Management Unit, Regional and Virgen de la Victoria University Hospitals, Málaga Biomedical Research Institute (IBIMA)-CIMES-UMA, 29010 Málaga, SpainIntercenter Medical Oncology Clinical Management Unit, Regional and Virgen de la Victoria University Hospitals, Málaga Biomedical Research Institute (IBIMA)-CIMES-UMA, 29010 Málaga, SpainIntercenter Medical Oncology Clinical Management Unit, Regional and Virgen de la Victoria University Hospitals, Málaga Biomedical Research Institute (IBIMA)-CIMES-UMA, 29010 Málaga, SpainIntercenter Medical Oncology Clinical Management Unit, Regional and Virgen de la Victoria University Hospitals, Málaga Biomedical Research Institute (IBIMA)-CIMES-UMA, 29010 Málaga, SpainIntercenter Medical Oncology Clinical Management Unit, Regional and Virgen de la Victoria University Hospitals, Málaga Biomedical Research Institute (IBIMA)-CIMES-UMA, 29010 Málaga, SpainIntercenter Medical Oncology Clinical Management Unit, Regional and Virgen de la Victoria University Hospitals, Málaga Biomedical Research Institute (IBIMA)-CIMES-UMA, 29010 Málaga, Spain; Department of Medicine and Pediatrics. Faculty of Medicine, University of Malaga, 29071 Malaga, SpainIntercenter Medical Oncology Clinical Management Unit, Regional and Virgen de la Victoria University Hospitals, Málaga Biomedical Research Institute (IBIMA)-CIMES-UMA, 29010 Málaga, Spain; Department of Medicine and Pediatrics. Faculty of Medicine, University of Malaga, 29071 Malaga, Spain; Department of Physiology and Pharmacology. Faculty of Medicine, University of Cantabria, and Valdecilla Health Research Institute (IDIVAL), 39011 Santander, Spain; Corresponding author at: Intercenter Medical Oncology Clinical Management Unit, Regional and Virgen de la Victoria University Hospitals, Málaga Biomedical Research Institute (IBIMA)-CIMES-UMA, 29010 Málaga, Spain.Intercenter Medical Oncology Clinical Management Unit, Regional and Virgen de la Victoria University Hospitals, Málaga Biomedical Research Institute (IBIMA)-CIMES-UMA, 29010 Málaga, Spain; Department of Surgical Specialties, Biochemical and Immunology. Faculty of Medicine, University of Málaga, 29071 Malaga, SpainMelatonin is a molecule with different antitumor actions in breast cancer and has been described as an inhibitor of vascular endothelial growth factor (VEGF). Despite the recognition of the key role exerted by VEGF in tumor angiogenesis, limitations arise when developing models to test new antiangiogenic molecules. Thus, the aim of this study was to develop rapid, economic, high capacity and easy handling angiogenesis assays to test the antiangiogenic effects of melatonin and demonstrate its most effective dose to neutralize and interfere with the angiogenic sprouting effect induced by VEGF and MCF-7. To perform this, 3D endothelial cell (HUVEC) spheroids and a chicken embryo chorioallantoic membrane (CAM) assay were used. The results showed that VEGF and MCF-7 were able to stimulate the sprouting of the new vessels in 3D endothelial spheroids and the CAM assay, and that melatonin had an inhibitory effect on angiogenesis. Specifically, as the 1 mM pharmacological dose was the only effective dose able to inhibit the formation of ramifications around the alginate in the CAM assay model, this inhibition was shown to occur in a dose-dependent manner. Taken together, these techniques represent novel tools for the development of antiangiogenic molecules such as melatonin, with possible implications for the therapy of breast cancer.http://www.sciencedirect.com/science/article/pii/S0753332222014305MelatoninVEGFEndothelial cellsHUVECMCF-7Spheroids
spellingShingle Aurora Laborda-Illanes
Lidia Sánchez-Alcoholado
Daniel Castellano-Castillo
Soukaina Boutriq
Isaac Plaza-Andrades
Lucía Aranega-Martín
Jesús Peralta-Linero
Emilio Alba
Alicia González-González
María Isabel Queipo-Ortuño
Development of in vitro and in vivo tools to evaluate the antiangiogenic potential of melatonin to neutralize the angiogenic effects of VEGF and breast cancer cells: CAM assay and 3D endothelial cell spheroids
Biomedicine & Pharmacotherapy
Melatonin
VEGF
Endothelial cells
HUVEC
MCF-7
Spheroids
title Development of in vitro and in vivo tools to evaluate the antiangiogenic potential of melatonin to neutralize the angiogenic effects of VEGF and breast cancer cells: CAM assay and 3D endothelial cell spheroids
title_full Development of in vitro and in vivo tools to evaluate the antiangiogenic potential of melatonin to neutralize the angiogenic effects of VEGF and breast cancer cells: CAM assay and 3D endothelial cell spheroids
title_fullStr Development of in vitro and in vivo tools to evaluate the antiangiogenic potential of melatonin to neutralize the angiogenic effects of VEGF and breast cancer cells: CAM assay and 3D endothelial cell spheroids
title_full_unstemmed Development of in vitro and in vivo tools to evaluate the antiangiogenic potential of melatonin to neutralize the angiogenic effects of VEGF and breast cancer cells: CAM assay and 3D endothelial cell spheroids
title_short Development of in vitro and in vivo tools to evaluate the antiangiogenic potential of melatonin to neutralize the angiogenic effects of VEGF and breast cancer cells: CAM assay and 3D endothelial cell spheroids
title_sort development of in vitro and in vivo tools to evaluate the antiangiogenic potential of melatonin to neutralize the angiogenic effects of vegf and breast cancer cells cam assay and 3d endothelial cell spheroids
topic Melatonin
VEGF
Endothelial cells
HUVEC
MCF-7
Spheroids
url http://www.sciencedirect.com/science/article/pii/S0753332222014305
work_keys_str_mv AT auroralabordaillanes developmentofinvitroandinvivotoolstoevaluatetheantiangiogenicpotentialofmelatonintoneutralizetheangiogeniceffectsofvegfandbreastcancercellscamassayand3dendothelialcellspheroids
AT lidiasanchezalcoholado developmentofinvitroandinvivotoolstoevaluatetheantiangiogenicpotentialofmelatonintoneutralizetheangiogeniceffectsofvegfandbreastcancercellscamassayand3dendothelialcellspheroids
AT danielcastellanocastillo developmentofinvitroandinvivotoolstoevaluatetheantiangiogenicpotentialofmelatonintoneutralizetheangiogeniceffectsofvegfandbreastcancercellscamassayand3dendothelialcellspheroids
AT soukainaboutriq developmentofinvitroandinvivotoolstoevaluatetheantiangiogenicpotentialofmelatonintoneutralizetheangiogeniceffectsofvegfandbreastcancercellscamassayand3dendothelialcellspheroids
AT isaacplazaandrades developmentofinvitroandinvivotoolstoevaluatetheantiangiogenicpotentialofmelatonintoneutralizetheangiogeniceffectsofvegfandbreastcancercellscamassayand3dendothelialcellspheroids
AT luciaaranegamartin developmentofinvitroandinvivotoolstoevaluatetheantiangiogenicpotentialofmelatonintoneutralizetheangiogeniceffectsofvegfandbreastcancercellscamassayand3dendothelialcellspheroids
AT jesusperaltalinero developmentofinvitroandinvivotoolstoevaluatetheantiangiogenicpotentialofmelatonintoneutralizetheangiogeniceffectsofvegfandbreastcancercellscamassayand3dendothelialcellspheroids
AT emilioalba developmentofinvitroandinvivotoolstoevaluatetheantiangiogenicpotentialofmelatonintoneutralizetheangiogeniceffectsofvegfandbreastcancercellscamassayand3dendothelialcellspheroids
AT aliciagonzalezgonzalez developmentofinvitroandinvivotoolstoevaluatetheantiangiogenicpotentialofmelatonintoneutralizetheangiogeniceffectsofvegfandbreastcancercellscamassayand3dendothelialcellspheroids
AT mariaisabelqueipoortuno developmentofinvitroandinvivotoolstoevaluatetheantiangiogenicpotentialofmelatonintoneutralizetheangiogeniceffectsofvegfandbreastcancercellscamassayand3dendothelialcellspheroids