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The Antiviral Agent Cidofovir Induces DNA Damage and Mitotic Catastrophe in HPV-Positive and -Negative Head and Neck Squamous Cell Carcinomas In Vitro

Cidofovir (CDV) is an antiviral agent with antiproliferative properties. The aim of our study was to investigate the efficacy of CDV in HPV-positive and -negative head and neck squamous cell carcinoma (HNSCC) cell lines and whether it is caused by a difference in response to DNA damage. Upon CDV tre...

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Autores principales: Verhees, Femke, Legemaate, Dion, Demers, Imke, Jacobs, Robin, Haakma, Wisse Evert, Rousch, Mat, Kremer, Bernd, Speel, Ernst Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678333/
https://www.ncbi.nlm.nih.gov/pubmed/31262012
http://dx.doi.org/10.3390/cancers11070919
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author Verhees, Femke
Legemaate, Dion
Demers, Imke
Jacobs, Robin
Haakma, Wisse Evert
Rousch, Mat
Kremer, Bernd
Speel, Ernst Jan
author_facet Verhees, Femke
Legemaate, Dion
Demers, Imke
Jacobs, Robin
Haakma, Wisse Evert
Rousch, Mat
Kremer, Bernd
Speel, Ernst Jan
author_sort Verhees, Femke
collection PubMed
description Cidofovir (CDV) is an antiviral agent with antiproliferative properties. The aim of our study was to investigate the efficacy of CDV in HPV-positive and -negative head and neck squamous cell carcinoma (HNSCC) cell lines and whether it is caused by a difference in response to DNA damage. Upon CDV treatment of HNSCC and normal oral keratinocyte cell lines, we carried out MTT analysis (cell viability), flow cytometry (cell cycle analysis), (immuno) fluorescence and western blotting (DNA double strand breaks, DNA damage response, apoptosis and mitotic catastrophe). The growth of the cell lines was inhibited by CDV treatment and resulted in γ-H2AX accumulation and upregulation of DNA repair proteins. CDV did not activate apoptosis but induced S- and G2/M phase arrest. Phospho-Aurora Kinase immunostaining showed a decrease in the amount of mitoses but an increase in aberrant mitoses suggesting mitotic catastrophe. In conclusion, CDV inhibits cell growth in HPV-positive and -negative HNSCC cell lines and was more profound in the HPV-positive cell lines. CDV treated cells show accumulation of DNA DSBs and DNA damage response activation, but apoptosis does not seem to occur. Rather our data indicate the occurrence of mitotic catastrophe.
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spelling pubmed-66783332019-08-19 The Antiviral Agent Cidofovir Induces DNA Damage and Mitotic Catastrophe in HPV-Positive and -Negative Head and Neck Squamous Cell Carcinomas In Vitro Verhees, Femke Legemaate, Dion Demers, Imke Jacobs, Robin Haakma, Wisse Evert Rousch, Mat Kremer, Bernd Speel, Ernst Jan Cancers (Basel) Article Cidofovir (CDV) is an antiviral agent with antiproliferative properties. The aim of our study was to investigate the efficacy of CDV in HPV-positive and -negative head and neck squamous cell carcinoma (HNSCC) cell lines and whether it is caused by a difference in response to DNA damage. Upon CDV treatment of HNSCC and normal oral keratinocyte cell lines, we carried out MTT analysis (cell viability), flow cytometry (cell cycle analysis), (immuno) fluorescence and western blotting (DNA double strand breaks, DNA damage response, apoptosis and mitotic catastrophe). The growth of the cell lines was inhibited by CDV treatment and resulted in γ-H2AX accumulation and upregulation of DNA repair proteins. CDV did not activate apoptosis but induced S- and G2/M phase arrest. Phospho-Aurora Kinase immunostaining showed a decrease in the amount of mitoses but an increase in aberrant mitoses suggesting mitotic catastrophe. In conclusion, CDV inhibits cell growth in HPV-positive and -negative HNSCC cell lines and was more profound in the HPV-positive cell lines. CDV treated cells show accumulation of DNA DSBs and DNA damage response activation, but apoptosis does not seem to occur. Rather our data indicate the occurrence of mitotic catastrophe. MDPI 2019-06-30 /pmc/articles/PMC6678333/ /pubmed/31262012 http://dx.doi.org/10.3390/cancers11070919 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Verhees, Femke
Legemaate, Dion
Demers, Imke
Jacobs, Robin
Haakma, Wisse Evert
Rousch, Mat
Kremer, Bernd
Speel, Ernst Jan
The Antiviral Agent Cidofovir Induces DNA Damage and Mitotic Catastrophe in HPV-Positive and -Negative Head and Neck Squamous Cell Carcinomas In Vitro
title The Antiviral Agent Cidofovir Induces DNA Damage and Mitotic Catastrophe in HPV-Positive and -Negative Head and Neck Squamous Cell Carcinomas In Vitro
title_full The Antiviral Agent Cidofovir Induces DNA Damage and Mitotic Catastrophe in HPV-Positive and -Negative Head and Neck Squamous Cell Carcinomas In Vitro
title_fullStr The Antiviral Agent Cidofovir Induces DNA Damage and Mitotic Catastrophe in HPV-Positive and -Negative Head and Neck Squamous Cell Carcinomas In Vitro
title_full_unstemmed The Antiviral Agent Cidofovir Induces DNA Damage and Mitotic Catastrophe in HPV-Positive and -Negative Head and Neck Squamous Cell Carcinomas In Vitro
title_short The Antiviral Agent Cidofovir Induces DNA Damage and Mitotic Catastrophe in HPV-Positive and -Negative Head and Neck Squamous Cell Carcinomas In Vitro
title_sort antiviral agent cidofovir induces dna damage and mitotic catastrophe in hpv-positive and -negative head and neck squamous cell carcinomas in vitro
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678333/
https://www.ncbi.nlm.nih.gov/pubmed/31262012
http://dx.doi.org/10.3390/cancers11070919
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