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

重新利用阿苯达唑:作为对 HPV 阴性头颈部鳞状细胞癌具有优先活性的化疗药物的新潜力

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作者:Farhad Ghasemi, Morgan Black, Frederick Vizeacoumar, Nicole Pinto, Kara M Ruicci, Carson Cao Son Huu Le, Matthew R Lowerison, Hon Sing Leong, John Yoo, Kevin Fung, Danielle MacNeil, David A Palma, Eric Winquist, Joe S Mymryk, Paul C Boutros, Alessandro Datti, John W Barrett, Anthony C Nichols

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 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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