Repurposing Albendazole: new potential as a chemotherapeutic agent with preferential activity against HPV-negative head and neck squamous cell cancer
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Farhad Ghasemi1, Morgan Black1,2, Frederick Vizeacoumar3, Nicole Pinto1,2, Kara M. Ruicci1,2, Carson Cao Son Huu Le4,5, Matthew R. Lowerison6,7, Hon Sing Leong4,5, John Yoo1,2, Kevin Fung1,2, Danielle MacNeil1,2, David A. Palma2, Eric Winquist2, Joe S. Mymryk1,2,8, Paul C. Boutros9,10, Alessandro Datti3, John W. Barrett1,2 and Anthony C. Nichols1,2
1Department of Otolaryngology, London Health Sciences Centre, London, Ontario, Canada
2Department of Oncology, London Health Sciences Centre, London, Ontario, Canada
3Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
4Department of Surgery, Schulich School of Medicine, Western University, London, Ontario, Canada
5Translational Prostate Cancer Research Laboratory, Lawson Health Research Institute, London, Ontario, Canada
6Department of Medical Biophysics, Western University, London, Ontario, Canada
7Robarts Research Institute, Western University, London, Ontario, Canada
8Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada
9Informatics and Biocomputing Program, Ontario Institute of Cancer Research, MaRS Centre, Toronto, Ontario, Canada
10Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
Anthony C. Nichols, email: [email protected]
Keywords: head and neck cancer, human papillomavirus, anti-helminthic, cell cycle arrest
Received: September 24, 2016 Accepted: April 11, 2017 Published: April 20, 2017
Albendazole is an anti-helminthic drug that has been shown to exhibit anti-cancer properties, however its activity in head and neck squamous cell cancer (HNSCC) was unknown. Using a series of in vitro assays, we assessed the ability of albendazole to inhibit proliferation in 20 HNSCC cell lines across a range of albendazole doses (1 nM–10 μM). Cell lines that responded to treatment were further examined for cell death, inhibition of migration and cell cycle arrest. Thirteen of fourteen human papillomavirus-negative HNSCC cell lines responded to albendazole, with an average IC50 of 152 nM. In contrast, only 3 of 6 human papillomavirus-positive HNSCC cell lines responded. Albendazole treatment resulted in apoptosis, inhibition of cell migration, cell cycle arrest in the G2/M phase and altered tubulin distribution. Normal control cells were not measurably affected by any dose tested. This study indicates that albendazole acts to inhibit the proliferation of human papillomavirus-negative HNSCC cell lines and thus warrants further study as a potential chemotherapeutic agent for patients suffering from head and neck cancer.
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