Targeting the Wnt/beta-catenin pathway with the antifungal agent ciclopirox olamine in a murine myeloma model.
BACKGROUND
Aberrant activation of Wnt/β-catenin signaling promotes the development of several types of cancer. Recently, it has been demonstrated that Wnt pathway is also activated in myeloma. Therefore, the Wnt/β-catenin signaling molecules are attractive candidates for development of targeted therapies for this disease.


METHODS
This study investigated the antitumor effect of ciclopirox olamine (CIC) in vitro and in vivo in a murine myeloma model.


RESULTS
CIC demonstrated major apoptotic activity in different human and murine myeloma and lymphoma cell lines, as well as in human primary cells. In addition, β-catenin expression was down-regulated when CIC was added to lymphoma cells. Interestingly, in vitro, a significant additive effect was seen with the combination of lenalidomide plus CIC as compared to single applications. In vivo, tumor growth, was significantly reduced and overall survival increased in mice treated with CIC as compared to untreated mice.


CONCLUSIONS
These results reveal a significant selective induction of apoptosis by CIC and suggest a significant in vivo effect against myeloma.
Department of Internal Medicine III, University Hospital Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.
Young
Y
Kim
Matthias
M
Schmidt
Tomoyuki
T
Endo
Desheng
D
Lu
Dennis
D
Carson
Ingo G H
IG
Schmidt-Wolf
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D000077768:Ciclopirox; D006801:Humans; D000077269:Lenalidomide; D008223:Lymphoma / Q000473:pathology; D051379:Mice; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology; D011728:Pyridones / Q000494:pharmacology*; D013792:Thalidomide / Q000031:analogs & derivatives / Q000494:pharmacology; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
D000935:Antifungal Agents; D011728:Pyridones; D051153:Wnt Proteins; D051176:beta Catenin; D000077768:Ciclopirox; D013792:Thalidomide; D000077269:Lenalidomide