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

被引:30
作者
Ghasemi, Farhad [1 ]
Black, Morgan [1 ,2 ]
Vizeacoumar, Frederick [3 ]
Pinto, Nicole [1 ,2 ]
Ruicci, Kara M. [1 ,2 ]
Le, Carson Cao Son Huu [4 ,5 ]
Lowerison, Matthew R. [6 ,7 ]
Leong, Hon Sing [4 ,5 ]
Yoo, John [1 ,2 ]
Fung, Kevin [1 ,2 ]
MacNeil, Danielle [1 ,2 ]
Palma, David A. [2 ]
Winquist, Eric [2 ]
Mymryk, Joe S. [1 ,2 ,8 ]
Boutros, Paul C. [9 ,10 ]
Datti, Alessandro [3 ]
Barrett, John W. [1 ,2 ]
Nichols, Anthony C. [1 ,2 ]
机构
[1] London Hlth Sci Ctr, Dept Otolaryngol, London, ON, Canada
[2] London Hlth Sci Ctr, Dept Oncol, London, ON, Canada
[3] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada
[4] Western Univ, Schulich Sch Med, Dept Surg, London, ON, Canada
[5] Lawson Hlth Res Inst, Translat Prostate Canc Res Lab, London, ON, Canada
[6] Western Univ, Dept Med Biophys, London, ON, Canada
[7] Western Univ, Robarts Res Inst, London, ON, Canada
[8] Univ Western Ontario, Dept Microbiol & Immunol, London, ON, Canada
[9] Ontario Inst Canc Res, MaRS Ctr, Informat & Biocomp Program, Toronto, ON, Canada
[10] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada
关键词
head and neck cancer; human papillomavirus; anti-helminthic; cell cycle arrest; IN-VITRO; HUMAN-PAPILLOMAVIRUS; CARCINOMA; DRUG; NANOPARTICLES; ABSORPTION; EFFICACY; GROWTH; MODEL;
D O I
10.18632/oncotarget.17292
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 mu M). 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.
引用
收藏
页码:71512 / 71519
页数:8
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