Uptake and antiproliferative effect of molecular iodine in the MCF-7 breast cancer cell line

Abstract

This study analyzes the uptake and antiproliferative effect of two different chemical forms of iodine, iodide (I K ) and molecular iodine (I 2 ), in MCF-7 cells, which are inducible for the Na C =I K 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, IK uptake is sustained and dependent on NIS, whereas I 2 uptake is transient with a maximal peak at 10 min and a final retention of 10% of total uptake. In contrast, no I K was taken up by NIH3T3 cells, and although I 2 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 I 2 is independent of NIS, PDS, Na C , 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 I 2 treatment. The administration of non-radiolabeled I 2 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 mM I 2 . In conclusion, these results demonstrate that I 2 uptake does not depend on NIS or PDS; they suggest that in mammary cancer cells, I 2 is taken up by a facilitated diffusion system and then covalently bound to lipids or proteins that, in turn, inhibit proliferation.

Signaling pathways involved in the antiproliferative effect of molecular iodine in normal and tumoral breast cells: evidence that 6-iodolactone mediates apoptotic effects

“…Our studies in the human tumoral mammary cell line MCF-7 show that I 2 is taken up by a facilitated diffusion system and is then incorporated into iodolipids similar to the 6-IL standard. Our data also show that both I 2 and 6-IL exert antiproliferative and apoptotic properties (Arroyo-Helguera et al 2006b); however, little is known about the molecular mechanisms involved in these effects.…”

“…6-IL was synthesized according to the procedure described previously (Arroyo-Helguera et al 2006b), where its purity was analyzed by reverse-phase HPLC and by ascending thin layer chromatography (TLC) using chloroform:methanol (97.5:2.5%, v/v). The spots were detected using iodine vapors.…”

Antineoplastic effect of iodine and iodide in dimethylbenz[a]anthracene-induced mammary tumors: association between lactoperoxidase and estrogen-adduct production

“…Several groups have postulated that the antineoplastic I 2 effect could be mediated by direct antioxidant/oxidant action at the mitochondrial level or by the formation of iodolipid intermediates such as 6-IL or iodohexadecanal (Dugrillon et al 1994, Shrivastava et al 2006, Rosner et al 2010. Our group has demonstrated that 6-IL formation in solid tumors (MNU) or cancerous cells (MCF-7) is associated with elevated concentrations of its precursor AA, and that 6-IL formation is independent of peroxidases when the supplement is I 2 (Arroyo- Helguera et al 2006). DMBA tumors were previously reported to contain high concentrations of AA and/or its metabolites (i.e.…”

Iodine levels are associated with oxidative stress and antioxidant status in pregnant women with hypertensive disease

“…During gestation, iodine deficiency is a risk factor of preeclampsia (13)(14)(15)(16)(17). Iodine per se has several functions: bactericidal, apoptosis inducer, antioxidant, and it has been recently involved in migration, invasion and trophoblast differentiation (18)(19)(20)(21)(22). Regarding the role of iodine as an antioxidant, it has been proposed that it can act directly as an electron donor and compete for binding sites with free radicals (23).…”