Leonard Christopher Schmeel1, Frederic Carsten Schmeel2, Young Kim1, Sabine Blaum-Feder1, Tomoyuki Endo3, Ingo G H Schmidt-Wolf4. 1. Department of Internal Medicine III, Center for Integrated Oncology, University Hospital Bonn, Bonn, Germany. 2. Department of Internal Medicine III, Center for Integrated Oncology, University Hospital Bonn, Bonn, Germany Department of Radiology, University Hospital Bonn, Bonn, Germany. 3. Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. 4. Department of Internal Medicine III, Center for Integrated Oncology, University Hospital Bonn, Bonn, Germany Ingo.Schmidt-Wolf@ukb.uni-bonn.de.
Abstract
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. Copyright
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 humanlymphoma cell lines, one murine and four humanmyeloma 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. Copyright
Authors: Jose A Sandoval; Alexey Tomilov; Sandipan Datta; Sonia Allen; Robert O'Donnell; Thomas Sears; Kevin Woolard; Dmytro Kovalskyy; James M Angelastro; Gino Cortopassi Journal: Pharmaceuticals (Basel) Date: 2020-11-24