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

被引：1

作者：

Ramos-Acosta, Carlos ^{[1
,2
]}

Huerta-Pantoja, Laura ^{[1
,2
]}

Salazar-Hidalgo, Milton Eduardo ^{[2
]}

Mayol, Elsa ^{[1
,2
]}

Jimenez-Vega, Selene ^{[1
,2
]}

Garcia-Pena, Pablo ^{[1
,2
]}

Jordi-Cruz, Jenifeer ^{[1
,2
]}

Baquero, Cristina ^{[3
]}

Porras, Almudena ^{[3
]}

Inigo-Rodriguez, Belen ^{[2
]}

Benavente, Celina M. ^{[1
,2
]}

Lopez-Pastor, Andrea R. ^{[4
,5
]}

Gomez-Delgado, Irene ^{[4
,5
]}

Urcelay, Elena ^{[4
,5
]}

Javier Candel, Francisco ^{[1
,6
]}

Anguita, Eduardo ^{[1
,2
]}

机构：

[1] Univ Complutense Madrid UCM, Med Sch, Dept Med, Plaza Ramon & Cajal S-N, Madrid 28040, Spain

[2] Hosp Clin San Carlos, Inst Invest Sanitaria San Carlos IdISSC, Hematol Dept, IML, Prof Martin Lagos S-N, Madrid 28040, Spain

[3] Univ Complutense Madrid UCM, Fac Pharm, Dept Biochem & Mol Biol, Inst Invest Sanitaria San Carlos IdISSC, Madrid 28040, Spain

[4] Inst Invest Sanitaria San Carlos IdISSC, Lab Genet & Mol Bases Complex Dis, Madrid 28040, Spain

[5] REI, Networks Cooperat Res Hlth Results RICORS, Madrid 28089, Spain

[6] Hosp Clin San Carlos, Inst Invest Sanitaria San Carlos IdISSC, Clin Microbiol & Infect Dis, Transplant Coordinat,IML, Madrid 28040, Spain

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2024年 / 25卷 / 09期

关键词：

multiple myeloma; tigecycline; bortezomib; ROS; cell cycle; antagonism; MULTIPLE-MYELOMA; PROTEASOME INHIBITOR; APOPTOSIS; AUTOPHAGY; MYC; TRANSLATION; EXPRESSION; RESISTANCE; INITIATION; CARCINOMA;

D O I：

10.3390/ijms25094887

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：27

共 73 条

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