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

Area of Science:

• Hematology
• Oncology
• Pharmacology

Background:

• Multiple myeloma is an incurable plasma cell cancer with frequent relapse and drug resistance.
• Bortezomib is a standard treatment, but resistance is a major clinical challenge.
• Tigecycline, an antibiotic, shows some activity against myeloma cells.

Purpose of the Study:

• To investigate the combined effect of tigecycline and bortezomib on multiple myeloma.
• To analyze the impact of this combination on cell death, mitochondrial function, and cell cycle progression.

Main Methods:

• Flow cytometry was used to assess apoptosis, autophagy, mitochondrial mass, and reactive oxygen species.
• Quantitative reverse transcription real-time PCR (RT-qPCR) and western blotting were employed to measure mitochondrial antioxidants and electron transport chain complexes.
• Seahorse assays and RT-qPCR characterized cell metabolism and mitochondrial activity.

Main Results:

• Tigecycline addition to bortezomib reduced apoptosis in a dose-dependent manner.
• The combination counteracted bortezomib's effects on the cell cycle and decreased autophagy/mitophagy markers.
• The combination reverted bortezomib-induced increases in mitochondrial superoxide and was associated with MYC upregulation.

Conclusions:

• The combination of tigecycline and bortezomib is not advisable for multiple myeloma treatment due to reduced efficacy.
• Caution is advised when using tigecycline in myeloma patients undergoing bortezomib therapy, especially for infection treatment, due to potential adverse impacts.