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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.
This article was published in the following journal.
Name: International journal of cancer
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Polyene macrolide antibiotic with unknown composition. It is obtained from Streptomyces aureofaciens. It is used as an antifungal agent, an antiprotozoal agent, and in the treatment of BENIGN PROSTATIC HYPERTROPHY.
The turning off of GENETIC TRANSCRIPTION in certain regions of CHROMATIN without changes in the DNA sequence. Typically epigenetic repression is a way that developmental changes are programmed at the cellular level.
Process by which micro-organisms adapt quickly to a preferred rapidly-metabolizable intermediate through the inhibition or repression of genes related to CATABOLISM of less preferred source(s).
A synthetic antifungal agent.
A triglyceride that is used as an antifungal agent.
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