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Biomed Pharmacother. 2017 Aug;92:403-411. doi: 10.1016/j.biopha.2017.05.097. Epub 2017 May 30.

Niclosamide induces apoptosis through mitochondrial intrinsic pathway and inhibits migration and invasion in human thyroid cancer in vitro.

Author information

1
Department of Endocrinology and Metabolism, Department of Liver Surgery, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China.
2
Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China.
3
Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.
4
Department of General Practice Medicine, West China Hospital, Sichuan University, Chengdu, China.
5
Department of Endocrinology and Metabolism, Department of Liver Surgery, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China. Electronic address: anzm1997@sina.com.
6
Department of Endocrinology and Metabolism, Department of Liver Surgery, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China; Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China. Electronic address: yeth1309@scu.edu.cn.

Abstract

The morbidity of thyroid cancer has been rising obviously throughout the world during the past years. Classic treatment procedure is generally curable for low risk differentiated thyroid cancer, but may lead to many postoperative complications. And low-level of thyroid stimulating hormone after surgery has side effects on both cardiovascular system and skeletal system. Furthermore effective treatment approaches for more aggressive differentiated thyroid cancer, poorly differentiated thyroid cancer and anaplastic thyroid cancer are absent, thus new candidates that can inhibit tumor growth and metastasis are urgently needed. In this study, niclosamide, an FDA approved anthelminthic drug, was evaluated for its anti-thyroid cancer activity in vitro. Niclosamide potently inhibited cell proliferation and induced apoptosis in human papillary thyroid cancer cell lines TPC-1 and BCPAP, as well as anaplastic thyroid cancer cell line ACT-1. In addition, the occurrence of TPC-1 apoptosis was correlated with activation of Bax and cleaved caspases-3, and inhibition of Bcl-2 and the mitochondrial membrane potential (ΔYm), indicating that niclosamide may induce apoptosis through a mitochondria-mediated intrinsic apoptotic pathway. Moreover, niclosamide markedly impaired TPC-1 cells and ACT-1 cells invasion. And we further found the inhibitory effect of TPC-1 was closely related with down-regulating of matrix metalloproteinase (MMP)-2 and -9 and up-regulating of tissue inhibitor of metalloproteinase (TIMP)-2. Taken together, these results demonstrated that niclosamide could be a potential agent for inhibiting the growth and metastasis of thyroid cancer.

KEYWORDS:

Apoptosis; Migration and invasion; Mitochondrial membrane potential; Niclosamide; Thyroid cancer

PMID:
28575805
DOI:
10.1016/j.biopha.2017.05.097
[Indexed for MEDLINE]

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