title: 1,25 dihydroxyvitamin D3 inhibits the proliferation of thyroid cancer stem-like cells via cell cycle arrest.
abstract: BACKGROUND
  An anti-proliferative effect of vitamin D has been reported in different carcinomas, including thyroid cancer. Cancer stem cells (CSCs), a very small fraction of cancer cells, are widely believed to be responsible for cancer initiation, relapse and metastasis.
  
  
  OBJECTIVE
  We addressed the question as to whether CSCs derived from the anaplastic thyroid carcinoma cell lines SW1736, C643, HTh74 and its doxorubicin- resistant subline HTh74R are also a target of vitamin D action.
  
  
  METHODS
  The effect of calcitriol on growth of HTh74, HTh74R, SW1736 and C643 cell lines was investigated by cell viability assays. In stem-enriched cells derived from thyro-spheres cell cycle analysis and apoptotic assays were performed. Furthermore, the role of calcitriol in the formation of cancer thyro-spheres and its putative differentiation-inducing effect were analysed.
  
  
  RESULTS
  CSCs isolated as thyro-spheres from all the four anaplastic thyroid carcinoma cells expressed vitamin D receptors as did their parental cells. Calcitriol inhibited proliferation of anaplastic thyroid carcinoma cells with a more pronounced effect on doxorubicin-resistant HTh74R cells, and it significantly reduced the capacity to form stem cell-derived spheres and decreased the size of these spheres that consist of CSCs and their progenitor cells. As revealed by cell cycle analysis, calcitriol induced G2/M phase arrest in thyro-sphere cells derived cells from HTh74, HTh74R and C643 but did not affect apoptosis. Finally, calcitriol altered morphology of CSCs.
  
  
  CONCLUSIONS
  Calcitriol inhibited the growth of CSCs derived from anaplastic thyroid cancer cells. It may also exert a pro-differentiation effect in thyroid CSCs.
authors.affiliation: a Division of Endocrinology, Department of Medicine, St. Hedwig Hospital and Charite , University Medicine , Berlin , Germany.
authors.forename: Wen
authors.initials: W
authors.lastname: Peng
authors.affiliation: a Division of Endocrinology, Department of Medicine, St. Hedwig Hospital and Charite , University Medicine , Berlin , Germany.
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.affiliation: a Division of Endocrinology, Department of Medicine, St. Hedwig Hospital and Charite , University Medicine , Berlin , Germany.
authors.forename: Rendong
authors.initials: R
authors.lastname: Zheng
authors.affiliation: a Division of Endocrinology, Department of Medicine, St. Hedwig Hospital and Charite , University Medicine , Berlin , Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Derwahl
mesh_terms: D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor / Q000187:drug effects; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D065646:Thyroid Carcinoma, Anaplastic / Q000188:drug therapy*; D013964:Thyroid Neoplasms / Q000188:drug therapy*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C118756:dihydroxy-vitamin D3; D014807:Vitamin D
keywords: Calcitriol; cancer stem-like cells; growth; thyroid carcinoma