Anti-proliferative effect and action mechanism of dexamethasone in human medullary thyroid cancer cell line

Endocr Res. 2011;36(4):149-57. doi: 10.3109/07435800.2011.593012.

Abstract

Introduction: Dexamethasone is known to inhibit the cell proliferation of certain transformed cell lines. In this study, the effect and action mechanism of dexamethasone were examined in the human medullary thyroid cancer cell line, TT cells.

Methods: TT cells were treated with or without dexamethasone. 5-Bromo-2'-deoxyuridine uptake assay was used to evaluate cell proliferation. Cell cycle and its regulatory proteins were assessed by flow cytometry and western blot analysis, respectively. Apoptosis was analyzed by Hoechst staining and Annexin V assay.

Results: Dexamethasone significantly reduced TT cell proliferation by 60% (p < 0.01). A substantial portion of cells was arrested at the G1 phase. The expression levels of cyclin D1, cyclin-dependent kinase (CDK)4, and CDK2 were decreased. In addition, the phosphorylation of retinoblastoma protein, which is a critical checkpoint protein in the transition of G1 to S phase, was decreased. On the other hand, the expression level of p27(Kip1), which is a cyclin/CDK inhibitor, was enhanced. Hoechst staining showed many fragmented nuclei in the dexamethasone-treated cells. The proportion of early apoptotic cells was also increased in the Annexin V assay.

Conclusion: Dexamethasone inhibited the proliferation of TT cells through cell cycle arrest at the G1 phase and increased apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Blotting, Western
  • Carcinoma, Medullary / drug therapy*
  • Carcinoma, Medullary / metabolism
  • Carcinoma, Medullary / pathology
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclin D1 / biosynthesis
  • Cyclin-Dependent Kinase 2 / biosynthesis
  • Cyclin-Dependent Kinase 4 / biosynthesis
  • Cyclin-Dependent Kinase Inhibitor p27 / biosynthesis
  • Dexamethasone / pharmacology*
  • Flow Cytometry
  • Glucocorticoids / pharmacology*
  • Humans
  • Thyroid Neoplasms / drug therapy*
  • Thyroid Neoplasms / metabolism
  • Thyroid Neoplasms / pathology

Substances

  • Glucocorticoids
  • Cyclin D1
  • Cyclin-Dependent Kinase Inhibitor p27
  • Dexamethasone
  • CDK2 protein, human
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase 4