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dc.creatorMedrano, M.es
dc.creatorContreras, M.es
dc.creatorCaballero Velázquez, Teresaes
dc.creatorMartínez, L.es
dc.creatorBejarano-García, J. A.es
dc.creatorCalderón Ruiz, Rocíoes
dc.creatorGarcía-Calderón, C. B.es
dc.creatorValle Rosado, Ivánes
dc.creatorPérez Simón, José Antonioes
dc.date.accessioned2024-04-11T13:32:54Z
dc.date.available2024-04-11T13:32:54Z
dc.date.issued2024
dc.identifier.citationMedrano, M., Contreras, M., Caballero Velázquez, T., Martínez, L., Bejarano-García, J.A., Calderón Ruiz, R.,...,Pérez Simón, J.A. (2024). Cannabinoids induce cell death in leukaemic cells through Parthanatos and PARP-related metabolic disruptions. British Journal of Cancer. https://doi.org/10.1038/s41416-024-02618-6.
dc.identifier.issn0007-0920es
dc.identifier.urihttps://hdl.handle.net/11441/156813
dc.description.abstractBACKGROUND: Several studies have described a potential anti-tumour effect of cannabinoids (CNB). CNB receptor 2 (CB2) is mostly present in hematopoietic stem cells (HSC). The present study evaluates the anti-leukaemic effect of CNB. METHODS: Cell lines and primary cells from acute myeloid leukaemia (AML) patients were used and the effect of the CNB derivative WIN-55 was evaluated in vitro, ex vivo and in vivo. RESULTS: We demonstrate a potent antileukemic effect of WIN-55 which is abolished with CB antagonists. WIN-treated mice, xenografted with AML cells, had better survival as compared to vehicle or cytarabine. DNA damage-related genes were affected upon exposure to WIN. Co-incubation with the PARP inhibitor Olaparib prevented WIN-induced cell death, suggesting PARPmediated apoptosis which was further confirmed with the translocation of AIF to the nucleus observed in WIN-treated cells. Nicotinamide prevented WIN-related apoptosis, indicating NAD+ depletion. Finally, WIN altered glycolytic enzymes levels as well as the activity of G6PDH. These effects are reversed through PARP1 inhibition. CONCLUSIONS: WIN-55 exerts an antileukemic effect through Parthanatos, leading to translocation of AIF to the nucleus and depletion of NAD+, which are reversed through PARP1 inhibition. It also induces metabolic disruptions. These effects are not observed in normal HSC.es
dc.formatapplication/pdfes
dc.format.extent13 p.es
dc.language.isoenges
dc.publisherNature Publishing Groupes
dc.relation.ispartofBritish Journal of Cancer.
dc.rightsAtribución 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.titleCannabinoids induce cell death in leukaemic cells through Parthanatos and PARP-related metabolic disruptionses
dc.typeinfo:eu-repo/semantics/articlees
dc.type.versioninfo:eu-repo/semantics/publishedVersiones
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses
dc.contributor.affiliationInstituto de Biomedicina de Sevilla (IBIS)es
dc.contributor.affiliationUniversidad de Sevilla. Departamento de Medicinaes
dc.contributor.affiliationUniversidad de Sevilla. Departamento de Genéticaes
dc.relation.projectIDDTS20/00165es
dc.relation.publisherversionhttps://www.nature.com/articles/s41416-024-02618-6es
dc.identifier.doi10.1038/s41416-024-02618-6es
dc.journaltitleBritish Journal of Canceres
dc.contributor.funderInstituto de Carlos IIIes

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