title: Anti-proliferative effect and action mechanism of dexamethasone in human medullary thyroid cancer cell line.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  Dexamethasone inhibited the proliferation of TT cells through cell cycle arrest at the G1 phase and increased apoptosis.
authors.affiliation: Department of Internal Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.
authors.forename: Yun Jae
authors.initials: YJ
authors.lastname: Chung
authors.forename: Ji In
authors.initials: JI
authors.lastname: Lee
authors.forename: Semin
authors.initials: S
authors.lastname: Chong
authors.forename: Ju Won
authors.initials: JW
authors.lastname: Seok
authors.forename: Sung Jun
authors.initials: SJ
authors.lastname: Park
authors.forename: Hye Won
authors.initials: HW
authors.lastname: Jang
authors.forename: Sun Wook
authors.initials: SW
authors.lastname: Kim
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Chung
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D018276:Carcinoma, Medullary / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000096:biosynthesis; D051357:Cyclin-Dependent Kinase 2 / Q000096:biosynthesis; D051358:Cyclin-Dependent Kinase 4 / Q000096:biosynthesis; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology*; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D005938:Glucocorticoids; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D003907:Dexamethasone; C495894:CDK2 protein, human; C495900:CDK4 protein, human; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4