@article{Braun2020-01-15Effec-47273,
  year={2020},
  doi={10.1002/ijc.32709},
  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},
  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}
}

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    <dcterms:issued>2020-01-15</dcterms:issued>
    <dc:creator>Braun, Julia A.</dc:creator>
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    <dc:creator>Blase, Johanna I.</dc:creator>
    <dc:language>eng</dc:language>
    <dc:creator>Hoppe-Seyler, Felix</dc:creator>
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    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2019-10-18T12:23:26Z</dc:date>
    <dc:creator>Frensemeier, Kristin</dc:creator>
    <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/47273"/>
    <dc:contributor>Bulkescher, Julia</dc:contributor>
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    <dc:creator>Herrmann, Anja L.</dc:creator>
    <dc:rights>Attribution 4.0 International</dc:rights>
    <dc:contributor>Hoppe-Seyler, Felix</dc:contributor>
    <dc:contributor>Blase, Johanna I.</dc:contributor>
    <dc:contributor>Hoppe-Seyler, Karin</dc:contributor>
    <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>Herrmann, Anja L.</dc:contributor>
    <dc:creator>Galy, Bruno</dc:creator>
    <dc:creator>Bulkescher, Julia</dc:creator>
    <dc:creator>Scheffner, Martin</dc:creator>
    <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>
    <dc:contributor>Frensemeier, Kristin</dc:contributor>
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    <dc:contributor>Galy, Bruno</dc:contributor>
    <dc:contributor>Braun, Julia A.</dc:contributor>
    <dc:contributor>Scheffner, Martin</dc:contributor>
    <dc:creator>Hoppe-Seyler, Karin</dc:creator>
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