title: MART-10, a newly synthesized vitamin D analog, represses metastatic potential of head and neck squamous carcinoma cells.
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.
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Chang Gung Memorial Hospital, Keelung, Taiwan, Republic of China.
authors.forename: Shih-Wei
authors.initials: SW
authors.lastname: Yang
authors.affiliation: Department of Oral and Maxillofacial Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China.
authors.forename: Chi-Ying
authors.initials: CY
authors.lastname: Tsai
authors.affiliation: Department of General Dentistry, Chang Gung Memorial Hospital, Chang Gung University, Keelung, Taiwan, Republic of China.
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Pan
authors.affiliation: General Surgery Department, Chang Gung Memorial Hospital, Keelung, Taiwan, Republic of China.
authors.forename: Chun-Nan
authors.initials: CN
authors.lastname: Yeh
authors.affiliation: Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China.
authors.forename: Jong-Hwei S
authors.initials: JH
authors.lastname: Pang
authors.affiliation: Faculty of Pharmaceutical Sciences, Teikyo University, Tokyo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Takano
authors.affiliation: Faculty of Pharmaceutical Sciences, Teikyo University, Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kittaka
authors.affiliation: Department of Anatomy, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China.
authors.forename: Horng-Heng
authors.initials: HH
authors.lastname: Juang
authors.affiliation: Endocrine Core Laboratory, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Tai C
authors.initials: TC
authors.lastname: Chen
authors.affiliation: General Surgery Department, Chang Gung Memorial Hospital, Keelung, Taiwan, Republic of China; Zebrafish Center, Chang Gung Memorial Hospital, Keelung, Taiwan, Republic of China.
authors.forename: Kun-Chun
authors.initials: KC
authors.lastname: Chiang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology*; D045744:Cell Line, Tumor; D002762:Cholecalciferol / Q000031:analogs & derivatives; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000737:chemistry* / Q000378:metabolism*; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000473:pathology*; D014807:Vitamin D / Q000031:analogs & derivatives / Q000138:chemical synthesis*
chemical_list: C569618:19-nor-2-(3-hydroxypropyl)-1,25-dihydroxyvitamin D3; D000970:Antineoplastic Agents; D014807:Vitamin D; D002762:Cholecalciferol; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: EMT; MART-10; head and neck cancer; metastasis; vitamin D analog