1,25 dihydroxyvitamin D3 inhibits the proliferation of thyroid cancer stem-like cells via cell cycle arrest

Endocr Res. 2016 May;41(2):71-80. doi: 10.3109/07435800.2015.1037048. Epub 2016 Mar 30.

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.

Objectives: 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.

Conclusion: Calcitriol inhibited the growth of CSCs derived from anaplastic thyroid cancer cells. It may also exert a pro-differentiation effect in thyroid CSCs.

Keywords: Calcitriol; cancer stem-like cells; growth; thyroid carcinoma.

MeSH terms

  • Cell Cycle Checkpoints / drug effects*
  • Cell Line, Tumor / drug effects
  • Humans
  • Neoplastic Stem Cells / drug effects*
  • Thyroid Carcinoma, Anaplastic / drug therapy*
  • Thyroid Neoplasms / drug therapy*
  • Vitamin D / analogs & derivatives*
  • Vitamin D / pharmacology

Substances

  • dihydroxy-vitamin D3
  • Vitamin D