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Exp Hematol. 2013 Sep;41(9):799-807.e4. doi: 10.1016/j.exphem.2013.04.012. Epub 2013 May 6.

Novel mTOR inhibitory activity of ciclopirox enhances parthenolide antileukemia activity.

Author information

1
Division of Hematology and Medical Oncology, Department of Medicine, Weill Medical College of Cornell University, New York, New York, USA.

Abstract

Ciclopirox, an antifungal agent commonly used for the dermatologic treatment of mycoses, has been shown recently to have antitumor properties. Although the exact mechanism of ciclopirox is unclear, its antitumor activity has been attributed to iron chelation and inhibition of the translation initiation factor eIF5A. In this study, we identify a novel function of ciclopirox in the inhibition of mTOR. As with other mTOR inhibitors, we show that ciclopirox significantly enhances the ability of the established preclinical antileukemia compound, parthenolide, to target acute myeloid leukemia. The combination of parthenolide and ciclopirox demonstrates greater toxicity against acute myeloid leukemia than treatment with either compound alone. We also demonstrate that the ability of ciclopirox to inhibit mTOR is specific to ciclopirox because neither iron chelators nor other eIF5A inhibitors affect mTOR activity, even at high doses. We have thus identified a novel function of ciclopirox that might be important for its antileukemic activity.

PMID:
23660068
PMCID:
PMC3809917
DOI:
10.1016/j.exphem.2013.04.012
[Indexed for MEDLINE]
Free PMC Article

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