Solamargine induces autophagy-mediated apoptosis and enhances bortezomib activity in multiple myeloma

Area of Science:

• Pharmacology
• Oncology
• Molecular Biology

Background:

• Multiple myeloma (MM) is an incurable plasma cell malignancy with limited treatment options.
• Conventional therapies for MM are associated with significant adverse events and drug resistance.
• Novel therapeutic agents and strategies are crucial for improving MM patient outcomes.

Purpose of the Study:

• To investigate the anti-MM activity of solamargine (SM), a steroidal alkaloid glycoside.
• To elucidate the mechanism of action of SM in MM cells, focusing on autophagy.
• To evaluate the potential synergistic effect of SM with bortezomib (BTZ) in MM treatment.

Main Methods:

• In vitro studies using MM cell lines (ARP-1, NCI-H929) treated with SM.
• RNA-sequencing (RNA-seq) analysis to identify gene expression changes.
• Autophagy inhibition studies using 3-Methyladenine.
• In vivo studies using an MM xenograft mouse model.
• Combination therapy studies with SM and bortezomib (BTZ).

Main Results:

• Solamargine (SM) suppressed MM cell viability and induced apoptosis in a dose- and time-dependent manner.
• SM treatment upregulated genes associated with cell death and autophagy, and activated autophagy in MM cells.
• Inhibition of autophagy significantly reduced SM's anti-MM effects.
• SM demonstrated synergistic effects with bortezomib (BTZ) in vitro and in vivo.
• SM showed single-agent efficacy and synergistic effects with BTZ in an MM xenograft model.

Conclusions:

• Solamargine (SM) exhibits anti-multiple myeloma (MM) activity, partly through the activation of autophagy.
• SM alone or in combination with bortezomib (BTZ) represents a promising therapeutic strategy for MM.
• Further research into SM as a novel anti-MM agent is warranted.