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Article

Tunicamycin as a Novel Redifferentiation Agent in Radioiodine Therapy for Anaplastic Thyroid Cancer

by
Yoon Ju Choi
1,7,†,
Jae-Eon Lee
2,†,
Hyun Dong Ji
1,7,†,
Bo-Ra Lee
2,†,
Sang Bong Lee
3,
Kil Soo Kim
2,4,
In-Kyu Lee
5,8,9,
Jungwook Chin
6,
Sung Jin Cho
6,8,
Jaetae Lee
1,8,
Sang-Woo Lee
1,8,*,
Jeoung-Hee Ha
7,* and
Yong Hyun Jeon
2,8,*
1
Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41566, Korea
2
Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41404, Korea
3
Vaccine Commerialization Center, Gyeongbuk Institute for Bioindustry, 88, Saneodanjigil, Pungsan-eup, Andong-si, Gyeongbuk 36618, Korea
4
College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Korea
5
Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Korea
6
New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41404, Korea
7
Department of pharmacology, School of Medicine, Kyungpook National University, Daegu 41405, Korea
8
Leading-Edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Daegu 41404, Korea
9
Research Institute of Aging and Metabolism, Kyungpook National University, Daegu 41404, Korea
*
Authors to whom correspondence should be addressed.
†
Y.J.C., J.-E.L., H.D.J. and B.-R.L. are equally contributed to this study.
Int. J. Mol. Sci. 2021, 22(3), 1077; https://doi.org/10.3390/ijms22031077
Submission received: 3 December 2020 / Revised: 12 January 2021 / Accepted: 18 January 2021 / Published: 22 January 2021
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Abstract

The silencing of thyroid-related genes presents difficulties in radioiodine therapy for anaplastic thyroid cancers (ATCs). Tunicamycin (TM), an N-linked glycosylation inhibitor, is an anticancer drug. Herein, we investigated TM-induced restoration of responsiveness to radioiodine therapy in radioiodine refractory ATCs. 125I uptake increased in TM-treated ATC cell lines, including BHT101 and CAL62, which was inhibited by KClO4, a sodium-iodide symporter (NIS) inhibitor. TM upregulated the mRNA expression of iodide-handling genes and the protein expression of NIS. TM blocked pERK1/2 phosphorylation in both cell lines, but AKT (protein kinase B) phosphorylation was only observed in CAL62 cells. The downregulation of glucose transporter 1 protein was confirmed in TM-treated cells, with a significant reduction in 18F-fluorodeoxyglucose (FDG) uptake. A significant reduction in colony-forming ability and marked tumor growth inhibition were observed in the combination group. TM was revealed to possess a novel function as a redifferentiation inducer in ATC as it induces the restoration of iodide-handling gene expression and radioiodine avidity, thereby facilitating effective radioiodine therapy.
Keywords: tunicamycin; sodium-iodide symporter; anaplastic thyroid cancer; redifferentiation; radioiodine therapy tunicamycin; sodium-iodide symporter; anaplastic thyroid cancer; redifferentiation; radioiodine therapy

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MDPI and ACS Style

Choi, Y.J.; Lee, J.-E.; Ji, H.D.; Lee, B.-R.; Lee, S.B.; Kim, K.S.; Lee, I.-K.; Chin, J.; Cho, S.J.; Lee, J.; et al. Tunicamycin as a Novel Redifferentiation Agent in Radioiodine Therapy for Anaplastic Thyroid Cancer. Int. J. Mol. Sci. 2021, 22, 1077. https://doi.org/10.3390/ijms22031077

AMA Style

Choi YJ, Lee J-E, Ji HD, Lee B-R, Lee SB, Kim KS, Lee I-K, Chin J, Cho SJ, Lee J, et al. Tunicamycin as a Novel Redifferentiation Agent in Radioiodine Therapy for Anaplastic Thyroid Cancer. International Journal of Molecular Sciences. 2021; 22(3):1077. https://doi.org/10.3390/ijms22031077

Chicago/Turabian Style

Choi, Yoon Ju, Jae-Eon Lee, Hyun Dong Ji, Bo-Ra Lee, Sang Bong Lee, Kil Soo Kim, In-Kyu Lee, Jungwook Chin, Sung Jin Cho, Jaetae Lee, and et al. 2021. "Tunicamycin as a Novel Redifferentiation Agent in Radioiodine Therapy for Anaplastic Thyroid Cancer" International Journal of Molecular Sciences 22, no. 3: 1077. https://doi.org/10.3390/ijms22031077

APA Style

Choi, Y. J., Lee, J.-E., Ji, H. D., Lee, B.-R., Lee, S. B., Kim, K. S., Lee, I.-K., Chin, J., Cho, S. J., Lee, J., Lee, S.-W., Ha, J.-H., & Jeon, Y. H. (2021). Tunicamycin as a Novel Redifferentiation Agent in Radioiodine Therapy for Anaplastic Thyroid Cancer. International Journal of Molecular Sciences, 22(3), 1077. https://doi.org/10.3390/ijms22031077

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