title: In vitro efficacy of cinnarizine against lymphoma and multiple myeloma.
abstract: OBJECTIVE
  Multiple myeloma, a well-known but still incurable disease, is a hematological malignancy of B-lymphocytes. While standard chemotherapy regimens have been used for years, novel agents, such as lenalidomide and bortezomib, have become an essential part of today's therapies. Nevertheless, new therapeutical strategies are required in the future. Aberrant activation of wingless-related integration site (WNT)/β-catenin signaling promotes the development of several types of cancer. Recently, it has been demonstrated that the WNT pathway is also activated in lymphoma and myeloma. Thus, the WNT signaling molecules are attractive candidates for the development of targeted therapies. To this extent, we recently confirmed that the diuretic agent ethacrynic acid (EA) and the antifungal agent ciclopirox olamine (CIC) inhibit WNT signaling. Cinnarizine has similar chemical features to those of CIC.
  
  
  METHODS
  Thus, in this study the antitumor effect of cinnarizine on myeloma and lymphoma cells was investigated by DiOC6 and propidium iodide (PI)-staining in flow cytometry.
  
  
  RESULTS
  Cinnarizine triggered a significant apoptotic activity in all tested myeloma and lymphoma cell lines in a concentration-dependent manner. Interestingly, healthy cells were mainly unaffected.
  
  
  CONCLUSIONS
  These results reveal a significant selective induction of apoptosis by cinnarizine that might result from an inhibition of WNT signaling and suggest an in vivo efficacy against lymphoma and myeloma.
authors: Department of Internal Medicine III, Center for Integrated Oncology (CIO), University Hospital Bonn, Bonn, Germany.
authors: Leonard Christopher
authors: LC
authors: Schmeel
authors: Department of Internal Medicine III, Center for Integrated Oncology (CIO), University Hospital Bonn, Bonn, Germany Department of Radiology, University Hospital Bonn, Bonn, Germany.
authors: Frederic Carsten
authors: FC
authors: Schmeel
authors: Department of Internal Medicine III, Center for Integrated Oncology (CIO), University Hospital Bonn, Bonn, Germany.
authors: Young
authors: Y
authors: Kim
authors: Department of Internal Medicine III, Center for Integrated Oncology (CIO), University Hospital Bonn, Bonn, Germany.
authors: Sabine
authors: S
authors: Blaum-Feder
authors: Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors: Tomoyuki
authors: T
authors: Endo
authors: Department of Internal Medicine III, Center for Integrated Oncology (CIO), University Hospital Bonn, Bonn, Germany Ingo.Schmidt-Wolf@ukb.uni-bonn.de.
authors: Ingo G H
authors: IG
authors: Schmidt-Wolf
mesh_terms: D045744:Cell Line, Tumor; D002936:Cinnarizine / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008223:Lymphoma / Q000378:metabolism / Q000473:pathology*; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: D051176:beta Catenin; D002936:Cinnarizine
keywords: Cinnarizine; WNT; cancer therapy; lymphoma; multiple myeloma