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Effects of the Antifungal Agent Ciclopirox in HPV-Positive Cancer Cells : Repression of Viral E6/E7 Oncogene Expression and Induction of Senescence and Apoptosis

Effects of the Antifungal Agent Ciclopirox in HPV-Positive Cancer Cells : Repression of Viral E6/E7 Oncogene Expression and Induction of Senescence and Apoptosis

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BRAUN, Julia A., Anja L. HERRMANN, Johanna I. BLASE, Kristin FRENSEMEIER, Julia BULKESCHER, Martin SCHEFFNER, Bruno GALY, Karin HOPPE-SEYLER, Felix HOPPE-SEYLER, 2020. Effects of the Antifungal Agent Ciclopirox in HPV-Positive Cancer Cells : Repression of Viral E6/E7 Oncogene Expression and Induction of Senescence and Apoptosis. In: International journal of cancer. 146(2), pp. 461-474. ISSN 0020-7136. eISSN 1097-0215. Available under: doi: 10.1002/ijc.32709

@article{Braun2020-01-15Effec-47273, title={Effects of the Antifungal Agent Ciclopirox in HPV-Positive Cancer Cells : Repression of Viral E6/E7 Oncogene Expression and Induction of Senescence and Apoptosis}, year={2020}, doi={10.1002/ijc.32709}, number={2}, volume={146}, issn={0020-7136}, journal={International journal of cancer}, pages={461--474}, author={Braun, Julia A. and Herrmann, Anja L. and Blase, Johanna I. and Frensemeier, Kristin and Bulkescher, Julia and Scheffner, Martin and Galy, Bruno and Hoppe-Seyler, Karin and Hoppe-Seyler, Felix} }

<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#" xmlns:foaf="http://xmlns.com/foaf/0.1/" xmlns:void="http://rdfs.org/ns/void#" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/47273"> <dc:language>eng</dc:language> <dc:creator>Braun, Julia A.</dc:creator> <dcterms:rights rdf:resource="https://kops.uni-konstanz.de/page/termsofuse"/> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2019-10-18T12:23:26Z</dc:date> <dc:creator>Hoppe-Seyler, Felix</dc:creator> <dc:contributor>Bulkescher, Julia</dc:contributor> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2019-10-18T12:23:26Z</dcterms:available> <dc:contributor>Frensemeier, Kristin</dc:contributor> <dc:contributor>Blase, Johanna I.</dc:contributor> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dc:creator>Galy, Bruno</dc:creator> <dc:contributor>Scheffner, Martin</dc:contributor> <dcterms:issued>2020-01-15</dcterms:issued> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> <dc:creator>Scheffner, Martin</dc:creator> <dc:contributor>Hoppe-Seyler, Karin</dc:contributor> <dc:creator>Herrmann, Anja L.</dc:creator> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/47273/1/Braun_2-kvjxg047hcaz6.pdf"/> <dc:contributor>Herrmann, Anja L.</dc:contributor> <dc:contributor>Galy, Bruno</dc:contributor> <dc:rights>terms-of-use</dc:rights> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dc:creator>Bulkescher, Julia</dc:creator> <dc:creator>Hoppe-Seyler, Karin</dc:creator> <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/47273/1/Braun_2-kvjxg047hcaz6.pdf"/> <dc:creator>Blase, Johanna I.</dc:creator> <dc:contributor>Hoppe-Seyler, Felix</dc:contributor> <dc:creator>Frensemeier, Kristin</dc:creator> <dcterms:abstract xml:lang="eng">The malignant growth of human papillomavirus (HPV)-positive cancer cells is dependent on the continuous expression of the viral E6/E7 oncogenes. Here, we examined the effects of iron deprivation on the phenotype of HPV-positive cervical cancer cells. We found that iron chelators, such as the topical antifungal agent ciclopirox (CPX), strongly repress HPV E6/E7 oncogene expression, both at the transcript and protein level. CPX efficiently blocks the proliferation of HPV-positive cancer cells by inducing cellular senescence. Although active mTOR signaling is considered to be critical for the cellular senescence response towards a variety of pro-senescent agents, CPX-induced senescence occurs under conditions of severely impaired mTOR signaling. Prolonged CPX treatment leads to p53-independent Caspase-3/7 activation and induction of apoptosis. CPX also eliminates HPV-positive cancer cells under hypoxic conditions through induction of apoptosis. Taken together, these results show that iron deprivation exerts profound anti-viral and anti-proliferative effects in HPV-positive cancer cells and suggest that iron chelators, such as CPX, possess therapeutic potential as HPV-inhibitory, pro-senescent and pro-apoptotic agents in both normoxic and hypoxic environments. This article is protected by copyright. All rights reserved.</dcterms:abstract> <dc:contributor>Braun, Julia A.</dc:contributor> <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/47273"/> <dcterms:title>Effects of the Antifungal Agent Ciclopirox in HPV-Positive Cancer Cells : Repression of Viral E6/E7 Oncogene Expression and Induction of Senescence and Apoptosis</dcterms:title> </rdf:Description> </rdf:RDF>

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