Tigecycline Opposes Bortezomib Effect on Myeloma Cells Decreasing Mitochondrial Reactive Oxygen Species Production

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dc.contributor.authorRamos Acosta, Carlos
dc.contributor.authorHuerta Pantoja, Laura
dc.contributor.authorSalazar Hidalgo, Milton Eduardo
dc.contributor.authorMayol, Elsa
dc.contributor.authorJiménez Vega, Selene
dc.contributor.authorGarcía Peña, Pablo
dc.contributor.authorJordi Cruz, Jenifeer
dc.contributor.authorBaquero, Cristina
dc.contributor.authorPorras Gallo, María Almudena
dc.contributor.authorÍñigo Rodríguez, Belén
dc.contributor.authorBenavente Cuesta, Celina
dc.contributor.authorCandel González, Francisco Javier
dc.contributor.authorAnguita Mandly, Eduardo Luis
dc.date.accessioned2024-07-04T09:35:04Z
dc.date.available2024-07-04T09:35:04Z
dc.date.issued2024-04-30
dc.description.abstractMultiple myeloma is an incurable plasma cell malignancy. Most patients end up relapsing and developing resistance to antineoplastic drugs, like bortezomib. Antibiotic tigecycline has activity against myeloma. This study analyzed tigecycline and bortezomib combination on cell lines and plasma cells from myeloma patients. Apoptosis, autophagic vesicles, mitochondrial mass, mitochondrial superoxide, cell cycle, and hydrogen peroxide were studied by flow cytometry. In addition, mitochondrial antioxidants and electron transport chain complexes were quantified by reverse transcription real-time PCR (RT-qPCR) or western blot. Cell metabolism and mitochondrial activity were characterized by Seahorse and RT-qPCR. We found that the addition of tigecycline to bortezomib reduces apoptosis in proportion to tigecycline concentration. Supporting this, the combination of both drugs counteracts bortezomib in vitro individual effects on the cell cycle, reduces autophagy and mitophagy markers, and reverts bortezomib-induced increase in mitochondrial superoxide. Changes in mitochondrial homeostasis and MYC upregulation may account for some of these findings. These data not only advise to avoid considering tigecycline and bortezomib combination for treating myeloma, but caution on the potential adverse impact of treating infections with this antibiotic in myeloma patients under bortezomib treatment.
dc.description.departmentDepto. de Medicina
dc.description.facultyFac. de Medicina
dc.description.fundingtypeDescuento UCM
dc.description.refereedTRUE
dc.description.sponsorshipFundación Hay Esperanza
dc.description.sponsorshipFundación Leucemia y Linfoma
dc.description.sponsorshipFundación Vistare
dc.description.statuspub
dc.identifier.citationRamos-Acosta, C.; Huerta-Pantoja, L.; Salazar-Hidalgo, M.E.; Mayol, E.; Jiménez-Vega, S.; García-Peña, P.; Jordi-Cruz, J.; Baquero, C.; Porras, A.; Íñigo- Rodríguez, B.; et al. Tigecycline Opposes Bortezomib Effect on Myeloma Cells Decreasing Mitochondrial Reactive Oxygen Species Production. Int. J. Mol. Sci. 2024, 25, 4887. https://doi.org/ 10.3390/ijms25094887
dc.identifier.doi10.3390/ijms25094887
dc.identifier.issn1422-0067
dc.identifier.officialurlhttps://doi.org/10.3390/ijms25094887
dc.identifier.pmid38732105
dc.identifier.relatedurlhttps://www.mdpi.com/1422-0067/25/9/4887
dc.identifier.urihttps://hdl.handle.net/20.500.14352/105610
dc.issue.number9
dc.journal.titleInternational journal of molecular sciences
dc.language.isoeng
dc.page.final27
dc.page.initial1
dc.publisherMDPI
dc.rightsAttribution 4.0 Internationalen
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.cdu616.15
dc.subject.keywordHematología
dc.subject.keywordMieloma
dc.subject.ucmHematología
dc.subject.unesco3205.04 Hematología
dc.subject.unesco2407 Biología Celular
dc.subject.unesco2415 Biología Molecular
dc.titleTigecycline Opposes Bortezomib Effect on Myeloma Cells Decreasing Mitochondrial Reactive Oxygen Species Production
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number25
dspace.entity.typePublication
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