Document Detail

Effects of theophylline on radioiodide uptake in MCF-7 breast cancer and NIS gene-transduced SNU-C5 colon cancer cells.
MedLine Citation:
PMID:  19409042     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: We investigated whether theophylline has the potential to increase radioiodide uptake in nonthyroidal cancer cells. MATERIALS AND 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.
Joon-Kee Yoon; Bok-Nam Park; Jin-Young Paik; Kyung-Ho Jung; Bong-Ho Ko; Kyung-Han Lee
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer biotherapy & radiopharmaceuticals     Volume:  24     ISSN:  1557-8852     ISO Abbreviation:  Cancer Biother. Radiopharm.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-05-04     Completed Date:  2009-08-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9605408     Medline TA:  Cancer Biother Radiopharm     Country:  United States    
Other Details:
Languages:  eng     Pagination:  201-8     Citation Subset:  IM    
Department of Nuclear Medicine and Molecular Imaging, Ajou University School of Medicine, Suwon, Korea.
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MeSH Terms
Biological Transport
Breast Neoplasms / genetics,  metabolism*,  therapy
Cell Line, Tumor
Colonic Neoplasms / genetics,  metabolism*,  therapy
Gene Therapy
Iodine Radioisotopes / pharmacokinetics*,  therapeutic use
Symporters / biosynthesis*,  genetics,  metabolism
Theophylline / pharmacology*
Transduction, Genetic
Tumor Cells, Cultured
Reg. No./Substance:
0/Iodine Radioisotopes; 0/Symporters; 0/sodium-iodide symporter; 58-55-9/Theophylline

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