title: Alpha-lipoic acid induces sodium iodide symporter expression in TPC-1 thyroid cancer cell line.
abstract: BACKGROUND
  Patients with metastatic thyroid cancers that do not uptake iodine need effective therapeutic option. Differentiation-inducing agents have been tried to restore functional expression of sodium iodide symporter (NIS) without success. Our objective was to assess the effect of alpha-lipoic acid (ALA), known as potential antioxidant, on expression of sodium iodide symporter in thyroid cancer cells.
  
  
  METHODS
  Human thyroid cancer-derived cell lines, TPC-1, were treated with ALA, and changes in NIS mRNA and protein expression were measured. ALA's effect on NIS gene promoter was evaluated, and functional NIS expression was assessed by iodide uptake assay.
  
  
  RESULTS
  Treatment with ALA increased NIS mRNA expression up to ten folds of control dose-dependently after 24 h of exposure. ALA increased NIS promoter activity, and increased iodide uptake by 1.6 fold. ALA induced expression of NIS protein, but had no significant effect on the plasma membrane trafficking. ALA increased phosphorylation of CREB and nuclear translocation of pCREB, and co-treatment of ALA and trichostatin A increased iodide uptake by three folds in TPC-1 cells.
  
  
  CONCLUSIONS
  ALA is a potential agent to increase NIS transcription in TPC-1. It could be used as an adjunctive agent to increase efficacy of radioiodine therapy if combined with a strategy to increase NIS protein trafficking to cell membrane.
authors.affiliation: Asan Institute for Life Science, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, Seoul 138-736, South Korea.
authors.forename: Hyun-Jeung
authors.initials: HJ
authors.lastname: Choi
authors.forename: Tae Yong
authors.initials: TY
authors.lastname: Kim
authors.forename: Sergio
authors.initials: S
authors.lastname: Ruiz-Llorente
authors.forename: Min Ji
authors.initials: MJ
authors.lastname: Jeon
authors.forename: Ji Min
authors.initials: JM
authors.lastname: Han
authors.forename: Won Gu
authors.initials: WG
authors.lastname: Kim
authors.forename: Young Kee
authors.initials: YK
authors.lastname: Shong
authors.forename: Won Bae
authors.initials: WB
authors.lastname: Kim
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D007454:Iodides / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D027981:Symporters / Q000235:genetics* / Q000378:metabolism*; D008063:Thioctic Acid / Q000494:pharmacology*; D013964:Thyroid Neoplasms / Q000473:pathology*; D000099209:Sodium-Iodide Symporters
chemical_list: D000975:Antioxidants; D007454:Iodides; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D027981:Symporters; D008063:Thioctic Acid; D000099209:Sodium-Iodide Symporters