Extra virgin olive oil contains a phenolic inhibitor of the histone demethylase LSD1/KDM1A
dc.contributor.author
dc.date.accessioned
2019-11-25T08:00:43Z
dc.date.available
2019-11-25T08:00:44Z
dc.date.issued
2019-07-19
dc.identifier.uri
dc.description.abstract
The lysine-specific histone demethylase 1A (LSD1) also known as lysine (K)-specific demethylase 1A (KDM1A) is a central epigenetic regulator of metabolic reprogramming in obesity-associated diseases, neurological disorders, and cancer. Here, we evaluated the ability of oleacein, a biophenol secoiridoid naturally present in extra virgin olive oil (EVOO), to target LSD1. Molecular docking and dynamic simulation approaches revealed that oleacein could target the binding site of the LSD1 cofactor flavin adenosine dinucleotide with high affinity and at low concentrations. At higher concentrations, oleacein was predicted to target the interaction of LSD1 with histone H3 and the LSD1 co-repressor (RCOR1/CoREST), likely disturbing the anchorage of LSD1 to chromatin. AlphaScreen-based in vitro assays confirmed the ability of oleacein to act as a direct inhibitor of recombinant LSD1, with an IC50 as low as 2.5 μmol/L. Further, oleacein fully suppressed the expression of the transcription factor SOX2 (SEX determining Region Y-box 2) in cancer stem-like and induced pluripotent stem (iPS) cells, which specifically occurs under the control of an LSD1-targeted distal enhancer. Conversely, oleacein failed to modify ectopic SOX2 overexpression driven by a constitutive promoter. Overall, our findings provide the first evidence that EVOO contains a naturally occurring phenolic inhibitor of LSD1, and support the use of oleacein as a template to design new secoiridoid-based LSD1 inhibitors
dc.format.mimetype
application/pdf
dc.language.iso
eng
dc.publisher
MDPI (Multidisciplinary Digital Publishing Institute)
dc.relation.isformatof
Reproducció digital del document publicat a: https://doi.org/10.3390/nu11071656
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Nutrients, 2019, vol. 11, núm. 7, p. 1656
dc.relation.ispartofseries
Articles publicats (D-CM)
dc.rights
Reconeixement 4.0 Internacional
dc.rights.uri
dc.source
Cuyàs, Elisabet Gumuzio, Juan Lozano Sánchez, Jesús Carreras, David Verdura, Sara Llorach Parés, Laura Sanchez Martinez, Melchor Selga Coma, Elisabet Pérez, Guillermo J. Scornik, Fabiana S. Brugada, Ramon Bosch Barrera, Joaquim Segura Carretero, Antonio Martin, Ángel G. Encinar, José Antonio Menéndez Menéndez, Javier Abel 2019 Extra virgin olive oil contains a phenolic inhibitor of the histone demethylase LSD1/KDM1A Nutrients 11 7 1656
dc.subject
dc.title
Extra virgin olive oil contains a phenolic inhibitor of the histone demethylase LSD1/KDM1A
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
030367
dc.type.peerreviewed
peer-reviewed
dc.identifier.eissn
2072-6643