Targeting the Wnt/beta-catenin pathway in multiple myeloma.
OBJECTIVE
Recent investigations have shown that the Wnt signaling pathway is constitutively activated in multiple myeloma (MM), thereby promoting an exaggerated cell proliferation. Thus, influencing the Wnt pathway might represent a promising target in myeloma treatment.


METHODS
The present study investigated whether a combination of ethacrynic acid (EA) and ciclopirox olamine (CIC) with piceatannol (PIC) would influence the Wnt pathway and viability of human and murine myeloma cell lines by using DiOC6 and propidium iodide (PI) staining, flow cytometry and immunoblotting.


RESULTS
The combination of EA with PIC as well as the combination of CIC with PIC had a significant additive effect on the vitality of myeloma cells compared to single-agent application, while healthy cells remained mainly unaffected. Additionally, EA and CIC altered the expression of β-catenin itself and its downstream factors.


CONCLUSIONS
A combination of Wnt inhibitors could lead to novel treatment options for MM patients.
Department of Internal Medicine III, Center for Integrated Oncology (CIO), University Hospital Bonn, Sigmund-Freud-Straße 25, 53105 Bonn, Germany. Ingo.Schmidt-Wolf@ukb.uni-bonn.de.
Leonard Christopher
LC
Schmeel
Frederic Carsten
FC
Schmeel
Young
Y
Kim
Tomoyuki
T
Endo
Desheng
D
Lu
Ingo G H
IG
Schmidt-Wolf
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D000077768:Ciclopirox; D003106:Colon / Q000187:drug effects; D004232:Diuretics / Q000494:pharmacology; D004357:Drug Synergism; D004976:Ethacrynic Acid / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D009101:Multiple Myeloma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011728:Pyridones / Q000494:pharmacology*; D013267:Stilbenes / Q000494:pharmacology*; D051153:Wnt Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051176:beta Catenin / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000935:Antifungal Agents; D004232:Diuretics; D011728:Pyridones; D013267:Stilbenes; D051153:Wnt Proteins; D051176:beta Catenin; D000077768:Ciclopirox; C041525:3,3',4,5'-tetrahydroxystilbene; D011505:Protein-Tyrosine Kinases; D004976:Ethacrynic Acid
MPC-11; Myeloma; OPM-2; RPMI-8226; U-266 cell lines; Wnt inhibitors; Wnt pathway; beta-catenin; signaling therapies