Title:Reposition of the Fungicide Ciclopirox for Cancer Treatment
Volume: 16
Issue: 2
Author(s): Zhu Huang and Shile Huang*
Affiliation:
- Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932,United States
Keywords:
Apoptosis, angiogenesis, cell invasion, cell motility, cell proliferation, ciclopirox, fungicide, lymphangiogenesis,
patent.
Abstract:
Background: Ciclopirox (CPX), a broad-spectrum fungicide, has been widely used to
treat fungal infection on the skin and nails for decades. Recent preclinical and clinical studies have
shown that CPX also possesses promising anticancer activity.
Objective: The objective of this study is to summarize the patents, the pharmacological and toxicological
properties, the anticancer activity, and the mechanisms of action of CPX and its derivatives
as anticancer agents.
Methods: PubMed and Google using the keywords “ciclopirox”, “cancer or tumor” and “patent”
were searched, and the identified literature was reviewed.
Results: Pharmacological and toxicological profiles from preclinical and clinical studies support
that systemic administration of CPX and its derivatives is feasible and safe for cancer treatment.
CPX exerts its anticancer activity by inhibiting cell proliferation, inducing apoptosis, suppressing
cell migration and invasion, and inhibiting angiogenesis and lymphangiogenesis. Mechanistically,
CPX impacts the expression or activities of multiple signaling molecules or pathways, such as ribonucleotide
reductase, Myc, DJ-1, Wnt/β-catenin, DOHH/eIF5A/PEAK1, VEGFR-3/ERK1/2,
ATR/Chk1/Cdc25A, and AMPK/TSC/mTORC1. Most of these effects are attributed to iron chelation
by CPX. Five patents have been retrieved: four patents on the development of CPX prodrugs
to improve the water solubility and bioavailability of CPX, and one patent on the methods of bladder
cancer treatment with CPX, CPX-O, or a CPX prodrug.
Conclusion: CPX has a great potential to be repositioned for cancer therapy.
