Dataset Information

Reposition of the Fungicide Ciclopirox for Cancer Treatment.

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.

SUBMITTER: Huang Z

PROVIDER: S-EPMC9175535 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Reposition of the Fungicide Ciclopirox for Cancer Treatment.

Huang Zhu Z Huang Shile S

Recent patents on anti-cancer drug discovery 20210101 2

<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Methods</h4>PubMe ...[more]

PMID: 33573561

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Project description:AimTo investigate the proteome changes of stem cells due to ciclopirox olamine (CPX) treatment compared to control and retinoic acid treated cells.MethodsStem cells (SCs) are cells, which have the ability to continuously divide and differentiate into various other kinds of cells. Murine embryonic stem cells (ESCs) and multipotent adult germline stem cells (maGSCs) were treated with CPX, which has been shown to have an antiproliferative effect on stem cells, and compared to stem cells treated with retinoic acid (RA), which is known to have a differentiating effect on stem cells. Classical proteomic techniques like 2-D gel electrophoresis and differential in-gel electrophoresis (DIGE) were used to generate 2D protein maps from stem cells treated with RA or CPX as well as from non-treated stem cells. The resulting 2D gels were scanned and the digitalized images were collated with the help of Delta 2D software. The differentially expressed proteins were analyzed by a MALDI-TOF-TOF mass spectrometer, and the identified proteins were investigated and categorized using bioinformatics.ResultsTreatment of stem cells with CPX, a synthetic antifungal clinically used to treat superficial mycoses, resulted in an antiproliferative effect in vitro, without impairment of pluripotency. To understand the mechanisms induced by CPX treatments which results in arrest of cell cycle without any marked effect on pluripotency, a comparative proteomics study was conducted. The obtained data revealed that the CPX impact on cell proliferation was accompanied with a significant alteration in stem cell proteome. By peptide mass fingerprinting and tandem mass spectrometry combined with searches of protein sequence databases, a set of 316 proteins was identified, corresponding to a library of 125 non-redundant proteins. With proteomic analysis of ESCs and maGSCs treated with CPX and RA, we could identify more than 90 single proteins, which were differently expressed in both cell lines. We could highlight, that CPX treatment of stem cells, with subsequent proliferation inhibition, resulted in an alteration of the expression of 56 proteins compared to non-treated cells, and 54 proteins compared to RA treated cells. Bioinformatics analysis of the regulated proteins demonstrated their involvement in various biological processes. To our interest, a number of proteins have potential roles in the regulation of cell proliferation either directly or indirectly. Furthermore the classification of the altered polypeptides according to their main known/postulated functions revealed that the majority of these proteins are involved in molecular functions like nucleotide binding and metal ion binding, and biological processes like nucleotide biosynthetic processes, gene expression, embryonic development, regulation of transcription, cell cycle processes, RNA and mRNA processing. Proteins, which are involved in nucleotide biosynthetic process and proteolysis, were downregulated in CPX treated cells compared to control, as well as in RA treated cells, which may explain the cell cycle arrest. Moreover, proteins which were involved in cell death, positive regulation of biosynthetic process, response to organic substance, glycolysis, anti-apoptosis, and phosphorylation were downregulated in RA treated cells compared to control and CPX treated cells.ConclusionThe CPX treatment of SCs results in downregulation of nucleotide binding proteins and leads to cell cycle stop without impairment of pluripotency.

Dataset Information

Reposition of the Fungicide Ciclopirox for Cancer Treatment.

Background

Objective

Methods

Results

Conclusion

Publications

Reposition of the Fungicide Ciclopirox for Cancer Treatment.

Similar Datasets

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