Abstract 2969: the Antiviral Agent Cidofovir Induces DNA Damage and Mitotic Catastrophe in HPV-positive and -Negative Head and Neck Squamous Cell Carcinomas in Vitro

Objectives: Cidofovir (CDV) is an antiviral agent with anti-proliferative properties and is suggested as treatment option in head and neck squamous cell carcinoma (HNSCC) patients to improve outcome and quality of life. The mechanisms underlying the effectivity of CDV are not completely understood. The aim of our study was to investigate the efficacy of CDV in HPV-positive and -negative HNSCC cell lines in vitro and whether it is caused by a difference in response to DNA damage.Materials and methods: Upon CDV treatment of HPV-positive and -negative HNSCC-, uterine cervical carcinoma (UCC)- and immortalized NOK- cell lines, cell viability was assessed with a MTT assay. Accumulation of DNA double strand breaks (DSBs) and activation of the DNA repair pathway were analyzed using immunofluorescence (IF) and Western blotting (WB), respectively. Apoptosis was detected by cleaved-PARP (WB) and mitotic catastrophe by phospho-Aurora Kinase and Cyclin B1 (IF).Results: All cell lines responded to CDV. Treatment resulted in γ-H2AX accumulation and upregulation of DNA repair proteins, especially in the HPV-positive cells. CDV did not induce PARP cleavage but induced Cyclin B1 expression. Phospho-Aurora Kinase immunostaining showed a decrease in number of mitoses but an increase in aberrant mitoses suggesting mitotic catastrophe upon CDV treatment.Conclusion: CDV inhibits cell growth in HPV-positive and -negative HNSCC and UCC cell lines which was more profound in HPV-positive cell lines. CDV treated cells showed accumulation of DNA DSBs. Although the DNA repair was activated, apoptosis did not occur. Rather our data indicate the occurrence of mitotic catastrophe.Citation Format: Ernst-Jan M. Speel, Femke Verhees, Dion Legemaate, Robin Jacobs, Wisse E. Haakma, Mat Rousch, Bernd Kremer. The antiviral agent Cidofovir induces DNA damage and mitotic catastrophe in HPV-positive and -negative head and neck squamous cell carcinomas in vitro [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2969.