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Enhanced Iodide Sequestration by 3‐Biphenyl‐5,6‐dihydroimidazo[2,1‐ b ]thiazole in Sodium/Iodide Symporter (NIS)‐Expressing Cells
Author(s) -
LecatGuillet Nathalie,
Ambroise Yves
Publication year - 2008
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200800052
Subject(s) - sodium iodide symporter , iodide , symporter , chemistry , iodine , sodium iodide , thiazole , biochemistry , stereochemistry , gene , transporter , inorganic chemistry , organic chemistry
The ability of the sodium/iodide symporter (NIS) to take up iodide has long provided the basis for cytoreductive gene therapy and cancer treatment with radioiodide. One of the major limitations of this approach is that radioiodide retention in NIS‐expressing cells is not sufficient for their destruction. We identified and characterized a small organic molecule capable of increasing iodide retention in HEK293 cells permanently transfected with human NIS cDNA (hNIS‐HEK293) and in the rat thyroid‐derived cell line FRTL‐5. In the presence of 3‐biphenyl‐4′‐yl‐5,6‐dihydroimidazo[2,1‐ b ]thiazole (ISA1), the transmembrane iodide concentration gradient was increased up to 4.5‐fold. Our experiments indicate that the imidazothiazole derivative acts either by inhibiting anion efflux mechanisms, or by promoting the relocation of iodide into subcellular compartments. This new compound is not only an attractive chemical tool to investigate the mechanisms of iodide flux at the cellular level, but also opens promising perspectives in the treatment of cancer after NIS gene transfer.