Flunarizine exhibits in vitro efficacy against lymphoma and multiple myeloma cells.
OBJECTIVE
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.


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.


CONCLUSIONS
Our results reveal a significant selective induction of apoptosis by flunarizine and suggest an in vivo effect against lymphoma and myeloma.
Department of Internal Medicine III, Center for Integrated Oncology, University Hospital Bonn, Bonn, Germany.
Leonard Christopher
LC
Schmeel
Department of Internal Medicine III, Center for Integrated Oncology, University Hospital Bonn, Bonn, Germany Department of Radiology, University Hospital Bonn, Bonn, Germany.
Frederic Carsten
FC
Schmeel
Department of Internal Medicine III, Center for Integrated Oncology, University Hospital Bonn, Bonn, Germany.
Young
Y
Kim
Department of Internal Medicine III, Center for Integrated Oncology, University Hospital Bonn, Bonn, Germany.
Sabine
S
Blaum-Feder
Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Tomoyuki
T
Endo
Department of Internal Medicine III, Center for Integrated Oncology, University Hospital Bonn, Bonn, Germany Ingo.Schmidt-Wolf@ukb.uni-bonn.de.
Ingo G H
IG
Schmidt-Wolf
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005444:Flunarizine / Q000494:pharmacology*; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy* / Q000473:pathology; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology
D005444:Flunarizine
Flunarizine; WNT; cancer therapy; lymphoma; multiple myeloma; pathway