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

Drug Des Devel Ther. 2016 Jun 17:10:1995-2002. doi: 10.2147/DDDT.S107256. eCollection 2016.


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; MART-10; head and neck cancer; metastasis; vitamin D analog.

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Carcinoma, Squamous Cell / chemistry
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / pathology*
  • Cell Line, Tumor
  • Cholecalciferol / analogs & derivatives
  • Down-Regulation
  • Epithelial-Mesenchymal Transition / drug effects*
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / physiopathology*
  • Humans
  • Matrix Metalloproteinase 9 / chemistry*
  • Matrix Metalloproteinase 9 / metabolism*
  • Neoplasm Metastasis / drug therapy
  • Neoplasm Metastasis / pathology*
  • Vitamin D / analogs & derivatives
  • Vitamin D / chemical synthesis*


  • 19-nor-2-(3-hydroxypropyl)-1,25-dihydroxyvitamin D3
  • Antineoplastic Agents
  • Vitamin D
  • Cholecalciferol
  • MMP9 protein, human
  • Matrix Metalloproteinase 9