RT Journal Article
T1 Tigecycline Opposes Bortezomib Effect on Myeloma Cells Decreasing Mitochondrial Reactive Oxygen Species Production
A1 Ramos Acosta, Carlos
A1 Huerta Pantoja, Laura
A1 Salazar Hidalgo, Milton Eduardo
A1 Mayol, Elsa
A1 Jiménez Vega, Selene
A1 García Peña, Pablo
A1 Jordi Cruz, Jenifeer
A1 Baquero, Cristina
A1 Porras Gallo, María Almudena
A1 Íñigo Rodríguez, Belén
A1 Benavente Cuesta, Celina
A1 Candel González, Francisco Javier
A1 Anguita Mandly, Eduardo Luis
AB 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.
PB MDPI
SN 1422-0067
YR 2024
FD 2024-04-30
LK https://hdl.handle.net/20.500.14352/105610
UL https://hdl.handle.net/20.500.14352/105610
LA eng
NO Ramos-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
NO Fundación Hay Esperanza
NO Fundación Leucemia y Linfoma
NO Fundación Vistare
DS Docta Complutense
RD 20 jul 2024