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Sulfasalazine suppresses thyroid cancer cell proliferation and metastasis through T-cell originated protein kinase.
Oncol Lett 2019; 18(4):3517-3526OL

Abstract

Thyroid cancer patients with radioactive iodine-refractory or rapidly progressing presentation require effective treatment. T-cell originated protein kinase (TOPK) is highly expressed in a number of different tumor types, where it promotes proliferation and metastasis. However, the expression of TOPK in thyroid cancer is poorly documented. Therefore, immunohistochemistry was used to detect the expression of TOPK in thyroid cancer tissues, and its clinical significance in this disease was investigated. Sulfasalazine, a targeted inhibitor of TOPK that directly binds the protein with a dissociation constant (Kd) of 228 µM, was also investigated using microscale thermophoresis. Sulfasalazine inhibited TOPK activity, as determined by an in vitro pull-down assay. Furthermore, sulfasalazine inhibited the proliferation and metastasis of thyroid cancer cells. The results indicated that TOPK may be a potential therapeutic target and diagnostic biomarker for thyroid cancer and may be used as an index to evaluate malignant thyroid nodules. Therefore, sulfasalazine is a potential novel compound for the targeted treatment of thyroid cancer.

Authors+Show Affiliations

Department of Internal Medicine, CR and WISCO General Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei 430080, P.R. China. Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.Department of Internal Medicine, CR and WISCO General Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei 430080, P.R. China.Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.Department of Internal Medicine, CR and WISCO General Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei 430080, P.R. China.Health and Family Planning Committee of Qingshan, Wuhan, Hubei 430080, P.R. China.Department of Internal Medicine, CR and WISCO General Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei 430080, P.R. China.Department of Internal Medicine, CR and WISCO General Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei 430080, P.R. China.Department of Internal Medicine, CR and WISCO General Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei 430080, P.R. China.Department of Internal Medicine, CR and WISCO General Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei 430080, P.R. China.Department of Internal Medicine, CR and WISCO General Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei 430080, P.R. China.Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.Department of Internal Medicine, CR and WISCO General Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei 430080, P.R. China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31516569

Citation

Zou, Ling, et al. "Sulfasalazine Suppresses Thyroid Cancer Cell Proliferation and Metastasis Through T-cell Originated Protein Kinase." Oncology Letters, vol. 18, no. 4, 2019, pp. 3517-3526.
Zou L, Gao Z, Zeng F, et al. Sulfasalazine suppresses thyroid cancer cell proliferation and metastasis through T-cell originated protein kinase. Oncol Lett. 2019;18(4):3517-3526.
Zou, L., Gao, Z., Zeng, F., Xiao, J., Chen, J., Feng, X., ... Lin, X. (2019). Sulfasalazine suppresses thyroid cancer cell proliferation and metastasis through T-cell originated protein kinase. Oncology Letters, 18(4), pp. 3517-3526. doi:10.3892/ol.2019.10721.
Zou L, et al. Sulfasalazine Suppresses Thyroid Cancer Cell Proliferation and Metastasis Through T-cell Originated Protein Kinase. Oncol Lett. 2019;18(4):3517-3526. PubMed PMID: 31516569.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sulfasalazine suppresses thyroid cancer cell proliferation and metastasis through T-cell originated protein kinase. AU - Zou,Ling, AU - Gao,Zhi, AU - Zeng,Fanfan, AU - Xiao,Juanjuan, AU - Chen,Junmei, AU - Feng,Xiaohong, AU - Chen,Di, AU - Fang,Ying, AU - Cui,Jing, AU - Liu,Yang, AU - Li,Zhi, AU - Zhu,Feng, AU - Duan,Qiuhong, AU - Lin,Xuan, Y1 - 2019/08/06/ PY - 2018/10/21/received PY - 2019/06/25/accepted PY - 2019/9/14/entrez PY - 2019/9/14/pubmed PY - 2019/9/14/medline KW - T-cell originated protein kinase KW - metastasis KW - proliferation KW - sulfasalazine KW - thyroid cancer SP - 3517 EP - 3526 JF - Oncology letters JO - Oncol Lett VL - 18 IS - 4 N2 - Thyroid cancer patients with radioactive iodine-refractory or rapidly progressing presentation require effective treatment. T-cell originated protein kinase (TOPK) is highly expressed in a number of different tumor types, where it promotes proliferation and metastasis. However, the expression of TOPK in thyroid cancer is poorly documented. Therefore, immunohistochemistry was used to detect the expression of TOPK in thyroid cancer tissues, and its clinical significance in this disease was investigated. Sulfasalazine, a targeted inhibitor of TOPK that directly binds the protein with a dissociation constant (Kd) of 228 µM, was also investigated using microscale thermophoresis. Sulfasalazine inhibited TOPK activity, as determined by an in vitro pull-down assay. Furthermore, sulfasalazine inhibited the proliferation and metastasis of thyroid cancer cells. The results indicated that TOPK may be a potential therapeutic target and diagnostic biomarker for thyroid cancer and may be used as an index to evaluate malignant thyroid nodules. Therefore, sulfasalazine is a potential novel compound for the targeted treatment of thyroid cancer. SN - 1792-1074 UR - https://www.unboundmedicine.com/medline/citation/31516569/Sulfasalazine_suppresses_thyroid_cancer_cell_proliferation_and_metastasis_through_T-cell_originated_protein_kinase DB - PRIME DP - Unbound Medicine ER -