Research Papers:
Anthelmintic mebendazole enhances cisplatin’s effect on suppressing cell proliferation and promotes differentiation of head and neck squamous cell carcinoma (HNSCC)
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Abstract
Fugui Zhang1,2, Yong Li1, Hongmei Zhang1,2, Enyi Huang1,2, Lina Gao1, Wenping Luo1,2, Qiang Wei2,3, Jiaming Fan2,3, Dongzhe Song2,4, Junyi Liao2,3, Yulong Zou2,3, Feng Liu2,3, Jianxiang Liu2,5, Jiayi Huang2,3, Dan Guo2,3, Chao Ma2,6, Xue Hu2,3, Li Li2,7, Xiangyang Qu2,3, Liqun Chen2,3, Xinyi Yu2,3, Zhicai Zhang2,5, Tingting Wu2,8, Hue H. Luu2, Rex C. Haydon2, Jinlin Song1, Tong-Chuan He1,2,3, Ping Ji1
1Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, and the Affiliated Hospital of Stomatology of Chongqing Medical University, Chongqing, China
2Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA
3Ministry of Education Key Laboratory of Diagnostic Medicine, and the Affiliated Hospitals of Chongqing Medical University, Chongqing, China
4Department of Conservative Dentistry and Endodontics, West China Hospital and West China School of Stomatology, Sichuan University, Chengdu, China
5Department of Orthopaedic Surgery, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
6Department of General Surgery, The Affiliated Zhongnan Hospital of Wuhan University, Wuhan, China
7Department of Biomedical Engineering, School of Bioengineering, Chongqing University, Chongqing, China
8Department of Neurosurgery, The Affiliated Zhongnan Hospital of Wuhan University, Wuhan, China
Correspondence to:
Tong-Chuan He, email: [email protected]
Ping Ji, email: [email protected]
Keywords: head and neck squamous cell carcinoma, mebendazole, drug repurposing, keratinization, differentiation therapy
Received: October 17, 2016 Accepted: January 09, 2017 Published: January 16, 2017
ABSTRACT
Head and neck squamous cell carcinoma (HNSCC) is one of the most common and aggressive types of human cancers worldwide. Nearly a half of HNSCC patients experience recurrence within five years of treatment and develop resistance to chemotherapy. Thus, there is an urgent clinical need to develop safe and novel anticancer therapies for HNSCC. Here, we investigate the possibility of repurposing the anthelmintic drug mebendazole (MBZ) as an anti-HNSCC agent. Using the two commonly-used human HNSCC lines CAL27 and SCC15, we demonstrate MBZ exerts more potent anti-proliferation activity than cisplatin in human HNSCC cells. MBZ effectively inhibits cell proliferation, cell cycle progression and cell migration, and induces apoptosis of HNSCC cells. Mechanistically, MBZ can modulate the cancer-associated pathways including ELK1/SRF, AP1, STAT1/2, MYC/MAX, although the regulatory outcomes are context-dependent. MBZ also synergizes with cisplatin in suppressing cell proliferation and inducing apoptosis of human HNSCC cells. Furthermore, MBZ is shown to promote the terminal differentiation of CAL27 cells and keratinization of CAL27-derived xenograft tumors. Our results are the first to demonstrate that MBZ may exert its anticancer activity by inhibiting proliferation while promoting differentiation of certain HNSCC cancer cells. It’s conceivable the anthelmintic drug MBZ can be repurposed as a safe and effective agent used in combination with other frontline chemotherapy drugs such as cisplatin in HNSCC treatment.
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