Repurposing Albendazole: new potential as a chemotherapeutic agent with preferential activity against HPV-negative head and neck squamous cell cancer

Abstract

// Farhad Ghasemi 1 , Morgan Black 1, 2 , Frederick Vizeacoumar 3 , Nicole Pinto 1, 2 , Kara M. Ruicci 1, 2 , Carson Cao Son Huu Le 4, 5 , Matthew R. Lowerison 6, 7 , Hon Sing Leong 4, 5 , John Yoo 1, 2 , Kevin Fung 1, 2 , Danielle MacNeil 1, 2 , David A. Palma 2 , Eric Winquist 2 , Joe S. Mymryk 1, 2, 8 , Paul C. Boutros 9, 10 , Alessandro Datti 3 , John W. Barrett 1, 2 and Anthony C. Nichols 1, 2 1 Department of Otolaryngology, London Health Sciences Centre, London, Ontario, Canada 2 Department of Oncology, London Health Sciences Centre, London, Ontario, Canada 3 Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada 4 Department of Surgery, Schulich School of Medicine, Western University, London, Ontario, Canada 5 Translational Prostate Cancer Research Laboratory, Lawson Health Research Institute, London, Ontario, Canada 6 Department of Medical Biophysics, Western University, London, Ontario, Canada 7 Robarts Research Institute, Western University, London, Ontario, Canada 8 Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada 9 Informatics and Biocomputing Program, Ontario Institute of Cancer Research, MaRS Centre, Toronto, Ontario, Canada 10 Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada Correspondence to: Anthony C. Nichols, email: Anthony.Nichols@lhsc.on.ca Keywords: head and neck cancer, human papillomavirus, anti-helminthic, cell cycle arrest Received: September 24, 2016      Accepted: April 11, 2017      Published: April 20, 2017 ABSTRACT 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 IC 50 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.