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An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
Flunarizine exhibits in vitro efficacy against lymphoma and multiple myeloma cells
Leonard Christopher Schmeel1, Frederic Carsten Schmeel2, Young Kim1
1Department of Internal Medicine III, Center for Integrated Oncology, University Hospital Bonn, Bonn, Germany.
Background/Aim:
Novel agents such as lenalidomide and bortezomib have significantly improved today's therapy of multiple myeloma. Despite recent innovations, new therapeutic options are needed. The Wingless-related integration site (WNT) pathway is aberrantly activated in lymphoma and myeloma and therefore renders WNT signaling molecules attractive for the development of targeted therapies. Flunarizine was used in this study as it has chemical features similar to those of other known WNT inhibitors and already proven proapoptotic properties in leukemia cells.
Materials And Methods:
The antitumor apoptotic effect of flunarizine at doses ranging from 0.1-200 μM was investigated on three human lymphoma cell lines, one murine and four human myeloma cell lines by 3'3-Dihexyloxacarbocyanine iodide and propidium iodide staining in flow cytometry.
Results:
Flunarizine induced significant apoptotic activity in all tested myeloma and lymphoma cell lines in a dose-dependent manner.
Conclusion:
Our results reveal a significant selective induction of apoptosis by flunarizine and suggest an in vivo effect against lymphoma and myeloma.
Insights
Flunarizine demonstrated significant apoptosis in multiple myeloma and lymphoma cells. This study suggests flunarizine as a potential targeted therapy for these hematologic malignancies.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Current multiple myeloma therapies, including lenalidomide and bortezomib, have improved outcomes.
- The Wingless-related integration site (WNT) pathway is dysregulated in lymphoma and myeloma, presenting a therapeutic target.
- Flunarizine, a WNT signaling inhibitor, exhibits proapoptotic properties in leukemia cells.
Purpose of the Study:
- To investigate the potential of flunarizine as a targeted therapy for multiple myeloma and lymphoma.
- To evaluate the WNT pathway's role in these hematologic malignancies.
Main Methods:
- Tested flunarizine's apoptotic effect on three human lymphoma and four human myeloma cell lines.
- Utilized flow cytometry with 3'3-Dihexyloxacarbocyanine iodide and propidium iodide staining.
- Assessed flunarizine doses ranging from 0.1 to 200 μM.
Main Results:
- Flunarizine induced significant apoptosis in all tested lymphoma and myeloma cell lines.
- The apoptotic effect was dose-dependent, with higher concentrations yielding greater cell death.
Conclusions:
- Flunarizine selectively induces apoptosis in multiple myeloma and lymphoma cells.
- Results suggest flunarizine may have therapeutic potential in vivo for these cancers.

