Mimetics of extra virgin olive oil phenols with anti-cancer stem cell activity
dc.contributor.author
dc.date.accessioned
2022-03-21T14:56:17Z
dc.date.available
2022-03-21T14:56:17Z
dc.date.issued
2020-11-09
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dc.description.abstract
The extra virgin olive oil (EVOO) dihydroxy-phenol oleacein is a natural inhibitor of multiple metabolic and epigenetic enzymes capable of suppressing the functional traits of cancer stem cells (CSC). Here, we used a natural product-inspired drug discovery approach to identify new compounds that phenotypically mimic the anti-CSC activity of oleacein. We coupled 3D quantitative structure-activity relationship-based virtual profiling with phenotypic analysis using 3D tumorsphere formation as a gold standard for assessing the presence of CSC. Among the top 20 computationally-predicted oleacein mimetics, four fulfilled the phenotypic endpoint of specifically suppressing the tumorsphere-initiating capacity of CSC, in the absence of significant cytotoxicity against differentiated cancer cells growing in 2D cultures in the same low micromolar concentration range. Of these, 3,4-dihydrophenetyl butyrate -a lipophilic ester conjugate of the hydroxytyrosol moiety of oleacein- and (E)-N-allyl-2-((5-nitrofuran-2-yl)methylene)hydrazinecarbothioamide) -an inhibitor of Trypanosoma cruzi triosephosphate isomerase- were also highly effective at significantly reducing the proportion of aldehyde dehydrogenase (ALDH)-positive CSC-like proliferating cells. Preservation of the mTOR/DNMT binding mode of oleacein was dispensable for suppression of the ALDH+-CSC functional phenotype in hydroxytyrosol-unrelated mimetics. The anti-CSC chemistry of complex EVOO phenols such as oleacein can be phenocopied through the use of mimetics capturing its physico-chemical properties
dc.format.extent
19 p.
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application/pdf
dc.language.iso
eng
dc.publisher
Impact Journals
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Reproducció digital del document publicat a: https://doi.org/10.18632/aging.202154
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Aging-Us, 2020, vol. 12, núm. 21, p. 21057-21075
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Articles publicats (IdIBGi)
dc.rights
Reconeixement 3.0 Espanya
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dc.source
Cuyàs, Elisabet Gumuzio, Juan Lozano Sánchez, Jesús Segura Carretero, Antonio Verdura, Sara Bosch Barrera, Joaquim Martin Castillo, Begoña Nonell-Canals, Alfons Llebaria, Amadeu Cabello, Silvia Serra, Carme Sanchez Martinez, Melchor Martin, Ángel G. Menéndez Menéndez, Javier Abel 2020 Mimetics of extra virgin olive oil phenols with anti-cancer stem cell activity Aging-Us 12 21 21057 21075
dc.title
Mimetics of extra virgin olive oil phenols with anti-cancer stem cell activity
dc.type
info:eu-repo/semantics/article
dc.rights.accessRights
info:eu-repo/semantics/openAccess
dc.type.version
info:eu-repo/semantics/publishedVersion
dc.identifier.doi
dc.identifier.idgrec
034583
dc.type.peerreviewed
peer-reviewed
dc.identifier.eissn
1945-4589