Title:Repositioning the Old Fungicide Ciclopirox for New Medical Uses
Volume: 22
Issue: 28
Author(s): Tao Shen and Shile Huang
Affiliation:
Keywords:
Ciclopirox, iron chelator, fungicide, cancer, diabetes, HIV.
Abstract: Background: Ciclopirox (CPX) has been used as an antifungal agent in various
formulations to treat superficial fungal infection for decades. Its effectiveness and safety in
treatments have been demonstrated by multiple studies. Methods: Here we briefly
summarize the pharmacological and toxicological properties of CPX as an antifungal agent,
the new medical uses of CPX, as well as the correspondent molecular mechanisms. Results:
Increasing evidence has demonstrated that CPX is able to inhibit tumor growth, ameliorate
diabetes and its complications, prevent human immunodeficiency virus (HIV) infection,
and improve age-associated cardiovascular defects. Interestingly, its antifungal activity and
all those newly observed effects are more or less related to its capability of chelating iron
and interfering with the related signaling pathways. Mechanistically, CPX is capable of
modulating the activities of certain enzymes or signaling pathways, such as ribonucleotide
reductase (RR), deoxyhypusine hydroxylase (DOHH)/eukaryotic translation initiation
factor 5A (eIF5A), Wnt/ β-catenin, hypoxia-inducible factor-1α (HIF-1 α)/vascular endothelial growth factor
(VEGF), vascular endothelial growth factor receptor 3 (VEGFR-3)/extracellular signal-regulated protein kinases
1/2, mammalian target of rapamycin, and cyclin dependent kinases (CDKs). Most of these activities are related
to its chelation of iron. Conclusion: CPX, as an antifungal agent, may be repositioned for treatment of cancer
and other human diseases.
