title: Effects of theophylline on radioiodide uptake in MCF-7 breast cancer and NIS gene-transduced SNU-C5 colon cancer cells.
abstract: BACKGROUND
  We investigated whether theophylline has the potential to increase radioiodide uptake in nonthyroidal cancer cells.
  
  
  METHODS
  MCF-7 cells that express endogenous sodium/iodide symporter (NIS) and SNU-C5 cells adenovirally transduced with the human NIS gene (SNU-C5/NIS) were treated with 10(-7)-2x10(-4) mol/L theophylline for 24 hours before incubation with (125)I, and then, radioiodide uptake and retention were measured. NIS expression was assessed by immunohistochemistry and Western blot analysis, using an antihuman NIS monoclonal antibody.
  
  
  RESULTS
  Theophylline at 10(-6)-2x10(-4) mol/L significantly and dose dependently augmented radioiodide uptake in MCF-7 cells and at 10(-6)-10(-5) mol/L in SNU-C5/NIS cells, without affecting radioiodide efflux. Abrogation by KClO(4)(-) demonstrated that the effect of theophylline occurred through specific iodide transport. Immunohistochemistry revealed dose-dependent increases of NIS staining in MCF-7 and SNU-C5/NIS cells by 10(-6)-10(-4) and 10(-6)-10(-5) mol/L theophylline, respectively. Western blot analysis demonstrated similar findings, showing increased expression of NIS on the membrane of SNU-C5/NIS and MCF-7 cells by theophylline treatment.
  
  
  CONCLUSIONS
  Theophylline can augment radioiodide uptake in breast cancer cells and NIS gene-transduced cancer cells through the upregulation of NIS expression. Therefore, further investigations are warranted to explore the potential utility of this phenomenon for enhancing radioiodide-based imaging and therapies of NIS gene-transduced cancer cells.
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Joon-Kee
authors.initials: JK
authors.lastname: Yoon
authors.forename: Bok-Nam
authors.initials: BN
authors.lastname: Park
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Paik
authors.forename: Kyung-Ho
authors.initials: KH
authors.lastname: Jung
authors.forename: Bong-Ho
authors.initials: BH
authors.lastname: Ko
authors.forename: Kyung-Han
authors.initials: KH
authors.lastname: Lee
mesh_terms: D001692:Biological Transport; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D015316:Genetic Therapy; D006801:Humans; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics* / Q000627:therapeutic use; D027981:Symporters / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D013806:Theophylline / Q000494:pharmacology*; D014161:Transduction, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D000099209:Sodium-Iodide Symporters
chemical_list: D007457:Iodine Radioisotopes; D027981:Symporters; D013806:Theophylline; D000099209:Sodium-Iodide Symporters