Uptake and antiproliferative effect of molecular iodine in the MCF-7 breast cancer cell line.
This study analyzes the uptake and antiproliferative effect of two different chemical forms of iodine, iodide (I-) and molecular iodine (I2), in MCF-7 cells, which are inducible for the Na+/I- symporter (NIS) and positive for pendrin (PDS). The mouse fibroblast cell line NIH3T3 was used as control. Our results show that in MCF-7 cells, I- uptake is sustained and dependent on NIS, whereas I2 uptake is transient with a maximal peak at 10 min and a final retention of 10% of total uptake. In contrast, no I- was taken up by NIH3T3 cells, and although I2 was captured with the same time pattern as in MCF-7 cells, its uptake was significantly lower, and it was not retained within the cell. The uptake of I2 is independent of NIS, PDS, Na+, and energy, but it is saturable and dependent on protein synthesis, suggesting a facilitated diffusion system. Radioiodine was incorporated into protein and lipid fractions only with I2 treatment. The administration of non-radiolabeled I2 and 6-iodo-5-hydroxy-8,11,14-eicosatrienoic acid (6-iodolactone, an iodinated arachidonic acid), but not KI, significantly inhibited proliferation of MCF-7 cells. Proliferation of NIH3T3 cells was not inhibited by 20 microM I2. In conclusion, these results demonstrate that I2 uptake does not depend on NIS or PDS; they suggest that in mammary cancer cells, I2 is taken up by a facilitated diffusion system and then covalently bound to lipids or proteins that, in turn, inhibit proliferation.
Arroyo-Helguera
O
O
Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla Km 15 Carretera Qro-SLP, Juriquilla, 76230 Querétaro, México.
Anguiano
B
B
Delgado
G
G
Aceves
C
C
D000818:Animals; D027321:Anion Transport Proteins / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D007454:Iodides / Q000493:pharmacokinetics*; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D009363:Neoplasm Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000076988:Sulfate Transporters; D027981:Symporters / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D000099209:Sodium-Iodide Symporters
D027321:Anion Transport Proteins; D007454:Iodides; D007457:Iodine Radioisotopes; D026901:Membrane Transport Proteins; D009363:Neoplasm Proteins; D000076988:Sulfate Transporters; D027981:Symporters; D000099209:Sodium-Iodide Symporters; C085609:SLC26A4 protein, human; C494849:Slc26a4 protein, mouse