Person:
Anguita Mandly, Eduardo Luis

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First Name
Eduardo Luis
Last Name
Anguita Mandly
URI
https://hdl.handle.net/20.500.14352/79480
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Medicina
Department
Medicina
Area
Medicina
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Author: Benavente Cuesta, Celina × Subject: 616.15 ×

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    Tigecycline Opposes Bortezomib Effect on Myeloma Cells Decreasing Mitochondrial Reactive Oxygen Species Production
    (International journal of molecular sciences, 2024) Ramos Acosta, Carlos; Huerta Pantoja, Laura; Salazar Hidalgo, Milton Eduardo; Mayol, Elsa; Jiménez Vega, Selene; García Peña, Pablo; Jordi Cruz, Jenifeer; Baquero, Cristina; Porras Gallo, María Almudena; Íñigo Rodríguez, Belén; Benavente Cuesta, Celina; Candel González, Francisco Javier; Anguita Mandly, Eduardo Luis
    Multiple 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.