{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:05:03Z","timestamp":1760144703135,"version":"build-2065373602"},"reference-count":73,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T00:00:00Z","timestamp":1714435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundaci\u00f3n Hay Esperanza","award":["GRANT-ESP-122"],"award-info":[{"award-number":["GRANT-ESP-122"]}]},{"name":"Fundaci\u00f3n Leucemia y Linfoma and Fundaci\u00f3n Vistare","award":["GRANT-ESP-122"],"award-info":[{"award-number":["GRANT-ESP-122"]}]},{"name":"Celgene International","award":["GRANT-ESP-122"],"award-info":[{"award-number":["GRANT-ESP-122"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms25094887","type":"journal-article","created":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T03:30:49Z","timestamp":1714534249000},"page":"4887","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Tigecycline Opposes Bortezomib Effect on Myeloma Cells Decreasing Mitochondrial Reactive Oxygen Species Production"],"prefix":"10.3390","volume":"25","author":[{"given":"Carlos","family":"Ramos-Acosta","sequence":"first","affiliation":[{"name":"Department of Medicine, Medical School, Universidad Complutense de Madrid (UCM), Plaza Ram\u00f3n y Cajal s\/n, 28040 Madrid, Spain"},{"name":"Hematology Department, IML, Instituto de Investigaci\u00f3n Sanitaria San Carlos (IdISSC), Hospital Cl\u00ednico San Carlos, Profesor Mart\u00edn Lagos s\/n, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Huerta-Pantoja","sequence":"additional","affiliation":[{"name":"Department of Medicine, Medical School, Universidad Complutense de Madrid (UCM), Plaza Ram\u00f3n y Cajal s\/n, 28040 Madrid, Spain"},{"name":"Hematology Department, IML, Instituto de Investigaci\u00f3n Sanitaria San Carlos (IdISSC), Hospital Cl\u00ednico San Carlos, Profesor Mart\u00edn Lagos s\/n, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8472-1355","authenticated-orcid":false,"given":"Milton Eduardo","family":"Salazar-Hidalgo","sequence":"additional","affiliation":[{"name":"Hematology Department, IML, Instituto de Investigaci\u00f3n Sanitaria San Carlos (IdISSC), Hospital Cl\u00ednico San Carlos, Profesor Mart\u00edn Lagos s\/n, 28040 Madrid, 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