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MART-10, a newly synthesized vitamin D analog, represses metastatic potential of head and neck squamous carcinoma cells

Authors Yang S, Tsai C, Pan Y, Yeh C, S.Pang J, Takano M, Kittaka A, Juang H, Chen TC, Chiang K

Received 26 February 2016

Accepted for publication 4 April 2016

Published 17 June 2016 Volume 2016:10 Pages 1995—2002

DOI https://doi.org/10.2147/DDDT.S107256

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Lucy Goodman

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Wei Duan


Shih-Wei Yang,1,* Chi-Ying Tsai,2,* Yi-Chun Pan,3 Chun-Nan Yeh,4 Jong-Hwei S Pang,5 Masashi Takano,6 Atsushi Kittaka,6 Horng-Heng Juang,7 Tai C Chen,8 Kun-Chun Chiang4,9

1Department of Otolaryngology – Head and Neck Surgery, Chang Gung Memorial Hospital, Keelung, 2Department of Oral and Maxillofacial Surgery, Chang Gung Memorial Hospital, Taoyuan, 3Department of General Dentistry, Chang Gung Memorial Hospital, Chang Gung University, Keelung, 4General Surgery Department, Chang Gung Memorial Hospital, Keelung, 5Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China; 6Faculty of Pharmaceutical Sciences, Teikyo University, Tokyo, Japan; 7Department of Anatomy, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China; 8Endocrine Core Laboratory, Boston University School of Medicine, Boston, MA, USA; 9Zebrafish Center, Chang Gung Memorial Hospital, Keelung, Taiwan, Republic of China

*These authors contributed equally to this work

Abstract: Even with multidisciplinary treatment, the prognosis and quality of life of patients diagnosed with head and neck squamous cell carcinoma (HNSCC) are still not satisfactory. Previously, 19-Nor-2α-(3-hydroxypropyl)-1α,25(OH)2D3 (MART-10), the new brand 1α,25(OH)2D3 analog, has been demonstrated to be an effective drug to inhibit HNSCC growth in vitro. Since most cancer patients die of metastasis, in this study, the antimetastatic effect of MART-10 on HNSCC was investigated. Our results reveal that both 1α,25(OH)2D3 and MART-10 effectively repressed the migration and invasion of HNSCC cells, with MART-10 being much more potent than 1α,25(OH)2D3. The antimetastatic effect of 1α,25(OH)2D3 and MART-10 was mediated by attenuation of epithelial–mesenchymal transition (EMT), which was supported by the finding that the expression of EMT-inducing transcriptional factors, Sail and Twist, was inhibited by 1α,25(OH)2D3 and MART-10. The upregulation of E-cadherin and downregulation of N-cadherin in FaDu cells induced by both drugs further confirmed the repression of EMT. In addition, 1α,25(OH)2D3 and MART-10 treatment inhibited intracellular MMP-9 expression and extracellular MMP activity in FaDu cells. Collectively, our results suggest that the less-calcemia 1α,25(OH)2D3 analog, MART-10, is a promising drug for HNSCC treatment. Further clinical studies are warranted.

Keywords:
EMT, head and neck cancer, vitamin D analog, metastasis, MART-10

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