dc.creator | Medrano, M. | es |
dc.creator | Contreras, M. | es |
dc.creator | Caballero Velázquez, Teresa | es |
dc.creator | Martínez, L. | es |
dc.creator | Bejarano-García, J. A. | es |
dc.creator | Calderón Ruiz, Rocío | es |
dc.creator | García-Calderón, C. B. | es |
dc.creator | Valle Rosado, Iván | es |
dc.creator | Pérez Simón, José Antonio | es |
dc.date.accessioned | 2024-04-11T13:32:54Z | |
dc.date.available | 2024-04-11T13:32:54Z | |
dc.date.issued | 2024 | |
dc.identifier.citation | Medrano, 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.issn | 0007-0920 | es |
dc.identifier.uri | https://hdl.handle.net/11441/156813 | |
dc.description.abstract | BACKGROUND: 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.format | application/pdf | es |
dc.format.extent | 13 p. | es |
dc.language.iso | eng | es |
dc.publisher | Nature Publishing Group | es |
dc.relation.ispartof | British Journal of Cancer. | |
dc.rights | Atribución 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.title | Cannabinoids induce cell death in leukaemic cells through Parthanatos and PARP-related metabolic disruptions | es |
dc.type | info:eu-repo/semantics/article | es |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Instituto de Biomedicina de Sevilla (IBIS) | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Medicina | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Genética | es |
dc.relation.projectID | DTS20/00165 | es |
dc.relation.publisherversion | https://www.nature.com/articles/s41416-024-02618-6 | es |
dc.identifier.doi | 10.1038/s41416-024-02618-6 | es |
dc.journaltitle | British Journal of Cancer | es |
dc.contributor.funder | Instituto de Carlos III | es |