title: Curcumin induces G2/M arrest, apoptosis, NF-κB inhibition, and expression of differentiation genes in thyroid carcinoma cells.
abstract: OBJECTIVE
  The therapy of unresectable advanced thyroid carcinomas shows unfavorable outcome. Constitutive nuclear factor-κB (NF-κB) activation in thyroid carcinomas frequently contributes to therapeutic resistance; the radioiodine therapy often fails due to the loss of differentiated functions in advanced thyroid carcinomas. Curcumin is known for its anticancer properties in a series of cancers, but only few studies have focused on thyroid cancer. Our aim was to evaluate curcumin's molecular mechanisms and to estimate if curcumin could be a new therapeutic option in advanced thyroid cancer.
  
  
  METHODS
  Human thyroid cancer cell lines TPC-1 (papillary), FTC-133 (follicular), and BHT-101 (anaplastic) were treated with curcumin. Using real-time PCR analysis, we investigated microRNA (miRNA) and mRNA expression levels. Cell cycle, Annexin V/PI staining, and caspase-3 activity analysis were performed to detect apoptosis. NF-κB p65 activity and cell proliferation were analyzed using appropriate ELISA-based colorimetric assay kits.
  
  
  RESULTS
  Treatment with 50 μM curcumin significantly increased the mRNA expression of the differentiation genes thyroglobulin (TG) and sodium iodide symporter (NIS) in all three cell lines and induced inhibition of cell proliferation, apoptosis, and decrease of NF-κB p65 activity. The miRNA expression analyses showed a significant deregulation of miRNA-200c, -21, -let7c, -26a, and -125b, known to regulate cell differentiation and tumor progression. Curcumin arrested cell growth at the G2/M phase.
  
  
  CONCLUSIONS
  Curcumin increases the expression of redifferentiation markers and induces G2/M arrest, apoptosis, and downregulation of NF-κB activity in thyroid carcinoma cells. Thus, curcumin appears to be a promising agent to overcome resistance to the conventional cancer therapy.
authors.affiliation: Institute of Pathology, University Hospital of Essen, University of Duisburg-Essen, Hufelandstr. 55, 45122, Essen, Germany. Suzan.Schwertheim@uk-essen.de.
authors.forename: Suzan
authors.identifier: http://orcid.org/0000-0002-0320-4653
authors.initials: S
authors.lastname: Schwertheim
authors.affiliation: Institute of Cell Biology (Cancer Research), Medical Faculty, University of Duisburg-Essen, Essen, Germany.
authors.forename: Frederik
authors.initials: F
authors.lastname: Wein
authors.affiliation: Institute of Cell Biology (Cancer Research), Medical Faculty, University of Duisburg-Essen, Essen, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Lennartz
authors.affiliation: Institute of Pathology, University Hospital of Essen, University of Duisburg-Essen, Hufelandstr. 55, 45122, Essen, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Worm
authors.affiliation: Institute of Pathology, University Hospital of Essen, University of Duisburg-Essen, Hufelandstr. 55, 45122, Essen, Germany.|West German Cancer Centre Essen (WTZE), Essen, Germany.
authors.forename: Kurt Werner
authors.initials: KW
authors.lastname: Schmid
authors.affiliation: Institute of Pathology, University Hospital of Essen, University of Duisburg-Essen, Hufelandstr. 55, 45122, Essen, Germany.
authors.forename: Sien-Yi
authors.initials: SY
authors.lastname: Sheu-Grabellus
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D060888:Real-Time Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000473:pathology*; D059467:Transcriptome
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D003474:Curcumin
keywords: Curcumin; G2/M arrest ; NF-κB; Thyroid cancer