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Three-dimensional cell metabolomics deciphers the anti-angiogenic properties of the radioprotectant amifostine

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dc.contributor.author Katsila, Theodora
dc.contributor.author Chasapi, Styliani A.
dc.contributor.author Gómez-Tamayo, José C.
dc.contributor.author Chalikiopoulou, Constantina
dc.contributor.author Siapi, Eleni
dc.contributor.author Moros, Giorgos
dc.contributor.author Zoumpoulakis, Panagiotis
dc.contributor.author Spyroulias, Georgios A.
dc.contributor.author Kardamakis, Dimitrios
dc.date.accessioned 2022-01-10T11:49:23Z
dc.date.available 2022-01-10T11:49:23Z
dc.date.issued 2021
dc.identifier.citation Katsila T, Chasapi SA, Gomez Tamayo JC, Chalikiopoulou C, Siapi E, Moros G, Zoumpoulakis P, Spyroulias GA, Kardamakis D. Three-dimensional cell metabolomics deciphers the anti-angiogenic properties of the radioprotectant amifostine. Cancers (Basel). 2021;13(12):2877. DOI: 10.3390/cancers13122877
dc.identifier.issn 2072-6694
dc.identifier.uri http://hdl.handle.net/10230/52176
dc.description.abstract Aberrant angiogenesis is a hallmark for cancer and inflammation, a key notion in drug repurposing efforts. To delineate the anti-angiogenic properties of amifostine in a human adult angiogenesis model via 3D cell metabolomics and upon a stimulant-specific manner, a 3D cellular angiogenesis assay that recapitulates cell physiology and drug action was coupled to untargeted metabolomics by liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy. The early events of angiogenesis upon its most prominent stimulants (vascular endothelial growth factor-A or deferoxamine) were addressed by cell sprouting measurements. Data analyses consisted of a series of supervised and unsupervised methods as well as univariate and multivariate approaches to shed light on mechanism-specific inhibitory profiles. The 3D untargeted cell metabolomes were found to grasp the early events of angiogenesis. Evident of an initial and sharp response, the metabolites identified primarily span amino acids, sphingolipids, and nucleotides. Profiles were pathway or stimulant specific. The amifostine inhibition profile was rather similar to that of sunitinib, yet distinct, considering that the latter is a kinase inhibitor. Amifostine inhibited both. The 3D cell metabolomics shed light on the anti-angiogenic effects of amifostine against VEGF-A- and deferoxamine-induced angiogenesis. Amifostine may serve as a dual radioprotective and anti-angiogenic agent in radiotherapy patients.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher MDPI
dc.relation.ispartof Cancers (Basel). 2021;13(12):2877
dc.rights © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title Three-dimensional cell metabolomics deciphers the anti-angiogenic properties of the radioprotectant amifostine
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.3390/cancers13122877
dc.subject.keyword 3D cellular angiogenesis assay
dc.subject.keyword Amifostine
dc.subject.keyword Anti-angiogenesis
dc.subject.keyword Drug repurposing
dc.subject.keyword Metabolomics
dc.subject.keyword Radioprotection
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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