Effects of the antifungal agent ciclopirox in HPV-positive cancer cells: repression of viral E6/E7 oncogene expression and induction of senescence and apoptosis
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...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2020
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| In: |
International journal of cancer
Year: 2019, Volume: 146, Issue: 2, Pages: 461-474 |
| ISSN: | 1097-0215 |
| DOI: | 10.1002/ijc.32709 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1002/ijc.32709 Verlag: https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.32709 
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| Author Notes: | Julia A. Braun, Anja L. Herrmann, Johanna I. Blase, Kristin Frensemeier, Julia Bulkescher, Martin Scheffner, Bruno Galy, Karin Hoppe‐Seyler and Felix Hoppe‐Seyler |
| Summary: | 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 prosenescent 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 antiviral and antiproliferative effects in HPV-positive cancer cells and suggest that iron chelators, such as CPX, possess therapeutic potential as HPV-inhibitory, prosenescent and proapoptotic agents in both normoxic and hypoxic environments. |
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| Item Description: | Online 11 Oct 2019 Gesehen am 09.01.2020 |
| Physical Description: | Online Resource |
| ISSN: | 1097-0215 |
| DOI: | 10.1002/ijc.32709 |