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. 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 À7 -2Â10 À4 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 À6 -2Â10 À4 mol=L significantly and dose dependently augmented radioiodide uptake in MCF-7 cells and at 10 À6 -10 À5 mol=L in SNU-C5=NIS cells, without affecting radioiodide efflux. Abrogation by KClO 4 À 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

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