Dtsch Med Wochenschr. 2004 Mar 19;129(12):641-5.

[Article in German]

Torremante P.

Source

dr.torremante@onlinemed.de

Endocr Relat Cancer. 2006 Dec;13(4):1147-58.

Arroyo-Helguera O, Anguiano B, Delgado G, Aceves C.

Source

Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla Km 15 Carretera Qro-SLP, Juriquilla, 76230 Querétaro, México.

Abstract

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.

Endocr Relat Cancer. 2008 Dec;15(4):1003-11. Epub 2008 Sep 30.

Arroyo-Helguera O, Rojas E, Delgado G, Aceves C.

Source

Instituto de Neurobiología, Boulevard Juriquilla 3001, Juriquilla, Querétaro 76230 Instituto de Investigaciones Biomédicas, Ciudad Universitaria, Universidad Nacional Autónoma de México, D F 04510, México.

Abstract

Previous reports have documented the antiproliferative properties of I(2) and the arachidonic acid (AA) derivative 6-iodolactone (6-IL) in both thyroid and mammary glands. In this study, we characterized the cellular pathways activated by these molecules and their effects on cell cycle arrest and apoptosis in normal (MCF-12F) and cancerous (MCF-7) breast cells. Low-to-moderate concentrations of I(2) (10-20 microM) cause G1 and G2/M phase arrest in MCF-12F and caspase-dependent apoptosis in MCF-7 cells. In normal cells, only high doses of I(2) (40 microM) induced apoptosis, and this effect was mediated by poly (ADP-ribose) polymerase-1 (PARP1) and the apoptosis-induced factor, suggesting an oxidative influence of iodine at high concentrations. Our data indicate that both I(2) and 6-IL trigger the same intracellular pathways and suggest that the antineoplasic effect of I(2) in mammary cancer involves the intracellular formation of 6-IL. Mammary cancer cells are known to contain high concentrations of AA, which might explain why I(2) exerts apoptotic effects at lower concentrations only in tumoral cells.

Hormones (Athens). 2010 Jan-Mar;9(1):60-6.

Gärtner R, Rank P, Ander B.

Source

Department of Endocrinology, University of Munich, Germany. roland.gaertner@med.uni.muenchen.de

Abstract

OBJECTIVE:

As we previously demonstrated, the inhibitory effect of iodine on thyroid cell growth is mediated by iodolactones, especially 6-iodo-5-hydroxy-eicosatrienoic acid (delta-iodolactone). In this communication we compare the effect of iodide, molecular iodine and delta-iodolactone on growth inhibition and apoptosis on three human thyroid carcinoma cell lines (B-CPAP cells, FTC-133 cells and 8505C cells) as well as on human breast cancer cells (MCF 7).

METHODS:

Thyroid carcinoma cells were cultured in Dulbecco’s modified Eagle’s medium (DMEM) and MCF 7 cells in Rowswell Park Memorial Institute (RPMI) culture medium, both containing 10% (v/v) Fetal Calf Serum (FCS), until they were confluent. Around 2000 cells were then distributed in 12-well plates and grown for 48 h in either DMEM (thyroid cancer cells) or in RPMI medium (MCF 7 cells) both containing 5% FCS. Thereafter, different concentrations of iodide, iodine or delta-iodolactone were added for 24 h. Growth rate was estimated by cell counting in a Coulter Counter adapted for epithelial cells. Apoptosis was determined by a mitochondrial potential assay.

RESULTS:

The growth rate of B-CPAP cells was unaffected by iodide, but was reduced by high concentreations of molecular iodine (100 and 500 microM). However, delta-iodolactone significantly reduced cell proliferation already with low concentrations (5 microM and 10 microM) and further in a dose-dependent manner up to 82%. FTC-133 and 8505C cells were unaffected by iodide, iodine or delta-iodolactone. In contrast, in MCF 7 cells, molecular iodine (100 microM) inhibited growth from 100% to 83% but delta-iodolactone (1, 5 and 10 microM) dose-dependently decreased growth rate from 100% to 82% and 62%, respectively. The inhibition of growth was through apoptosis, and not necrosis, as the amount of apoptotic cells corresponded to the growth inhibition.

CONCLUSION:

delta-Iotaodolactone seems to be the main iodocompound which can inhibit growth and induce apoptosis in B-CPAP cells as well as in MCF 7 breast cancer cells.

Prostaglandins Other Lipid Mediat. 2009 Jun;89(1-2):34-42. Epub 2009 Apr 10.

Nuñez-Anita RE, Arroyo-Helguera O, Cajero-Juárez M, López-Bojorquez L, Aceves C.

Source

Instituto de Neurobiología, Universidad Nacional Autónoma de México, Juriquilla Querétaro, Mexico.

Abstract

Recently we and other groups have shown that molecular iodine (I(2)) exhibits potent antiproliferative and apoptotic effects in mammary cancer models. In the human breast cancer cell line MCF-7, I(2) treatment generates iodine-containing lipids similar to 6-iodo-5-hydroxy-eicosatrienoic acid and the 6-iodolactone (6-IL) derivative of arachidonic acid (AA), and it significantly decreases cellular proliferation and induces caspase-dependent apoptosis. Several studies have shown that AA is a natural ligand of the peroxisome proliferator-activated receptors (PPARs), which are nuclear transcription factors thought to participate in regulating cancer cell proliferation. Our results show that in MCF-7 cells: (1) 6-IL binds specifically and with high affinity to PPAR proteins (EMSA assays), (2) 6-IL activates both transfected (by transactivation assays) and endogenous (by lipid accumulation) peroxisome proliferator response elements, and (3) 6-IL supplementation increases PPAR gamma and decreases PPAR alpha expression. These results implicate PPARs in a molecular mechanism by which I(2), through formation of 6-IL, inhibits the growth of human breast cancer cells.