Pablo García-Solís

Inhibition of N-methyl-N-nitrosourea-induced mammary carcinogenesis by molecular iodine (I2) but not by iodide (I − ) treatment Evidence that I2 prevents cancer promotion

We analyzed the effect of molecular iodine (I2), potassium iodide (KI) and a subclinical concentration of thyroxine (T4) on the induction and promotion of mammary cancer induced by N-methyl-N-nitrosourea. Virgin Sprague-Dawley rats received short or continuous treatment. Continuous I2 treated rats exhibited a strong and persistent reduction in mammary cancer incidence (30%) compared to controls (72.7%). Interruption of short or long term treatments resulted in a higher incidence in mammary cancer compared to the control groups. The protective effect of I2 was correlated with the highest expression of the I-/Cl- transporter pendrin and with the lowest levels of lipoperoxidation expression in mammary glands. Triiodothyronine serum levels and Na+/I- symporter, lactoperoxidase, or p53 expression did not show any changes. In conclusion continuous I2 treatment has a potent antineoplastic effect on the progression of mammary cancer and its effect may be related to a decrease in the oxidative cell environment.

5'Deiodinase in two breast cancer cell lines: effect of triiodothyronine, isoproterenol and retinoids

Thyroid hormones participate in the regulation of growth, development and energy expenditure of vertebrates. Type I (D1) and type II 5deiodinases catalyze the peripheral conversion of the thyroid prohormone thyroxine to the active form triiodothyronine (T3). D1 is expressed in organs like liver, thyroid, and lactating mammary gland. This enzyme is regulated in an organ-specific manner by a wide number of factors like carbohydrates, T3, thyrotropin, and catecholamines. However, it has been shown that in several types of cancer the expression of D1 is reduced, lost, or regulated by different components. In the present work we describe the expression and regulation of 5deiodinases in two breast cancer cell lines: MCF-7 (ovarian hormone-dependent) and MDA-MB-231 (ovarian hormone-independent). Our results showed that MCF-7 cells expressed D1 activity ( approximately 10 pmol I(-)/mg protein per h), which was stimulated only by retinoic acid treatments, but not by T3 or the beta-adrenergic agonist isoproterenol. In MDA-MB-231 cells, deiodinase activity was not detected in control conditions nor under any of these treatments. These results support the notion that D1 expression could represent a sensitive differentiation marker.

Antineoplastic effect of iodine in mammary cancer: participation of 6-iodolactone (6-IL) and peroxisome proliferator-activated receptors (PPAR)

IntroductionStudies in mammary cancer demonstrated that moderately high concentrations of molecular iodine (I2) have a antiproliferative and apoptotic effect either in vivo as in vitro, however the cellular intermediated involved in these effects has not been elucidated.MethodsVirgin Sprague-Dawley rats were treated with methyl-nitrosourea (MNU: single dose ip, 50 mg/Kg bw) and the participation of arachidonic acid (AA) and PPAR receptors in the antineoplasic effect of I2 where analyzed.ResultsI2-treated rats for four weeks exhibited a significant reduction in the incidence (62.5 vs. 100%) and size (0.87 ± 0.98 vs 1.96 ± 1.5 cm3) of mammary tumors. HPLC analysis showed that tumoral but not normal mammary tissue contained an elevated basal concentration of AA and significantly more AA-iodinated called 6-iodolactone (6-IL) after chronic I2 treatment. Tumors from I2-treated rats showed fewer cells positive to proliferating cell nuclear antigen, lower blood vessel density, as well as decreases in vascular endothelial growth factor, urokinase-type plasminogen activator, and PPAR type alpha (PPARα). These same tumors showed increases in the cell death markers, TUNEL-positive cells (p < 0.05) and the enzyme caspase-3 (trend), as well as significant induction of PPAR type gamma (PPARγ).ConclusionTogether, these data demonstrate that the antineoplasic effect of iodine involves 6-IL formation and PPARγ induction.

Inhibition of intrathyroidal dehalogenation by iodide

Iodide is a trace element and a key component of thyroid hormones (TH). The availability of this halogen is the rate-limiting step for TH synthesis; therefore, thyroidal iodide uptake and recycling during TH synthesis are of major importance in maintaining an adequate supply. In the rat, the thyroid gland co-expresses a distinctive pair of intrathyroidal deiodinating enzymes: the thyroid iodotyrosine dehalogenase (tDh) and the iodothyronine deiodinase type 1 (ID1). In the present work, we studied the activity of these two dehalogenases in conditions of hypo- and hyperthyroidism as well as during acute and chronic iodide administration in both intact and hypophysectomized (HPX) rats. In order to confirm our observations, we also measured the mRNA levels for both dehalogenases and for the sodium/iodide symporter, the protein responsible for thyroidal iodide uptake. Our results show that triiodothyronine differentially regulates tDh and ID1 enzymatic activities, and that both acute and chronic iodide administration significantly decreases rat tDh and ID1 activities and mRNA levels. Conversely, both enzymatic activities increase when intrathyroidal iodide is pharmacologically depleted in TSH-replaced HPX rats. These results show a regulatory effect by iodide on the intrathyroidal dehalogenating enzymes and suggest that they contribute to the iodide-induced autoregulatory processes involved in the Wolff-Chaikoff effect.

Iodine Nutrition Status in Pregnant Women in Mexico

BACKGROUNDnIodine nutrition during pregnancy has become an important public health concern because of the deleterious impact of iodine deficiency on brain development during fetal and early postnatal life. Iodine nutrition status can be assessed in a population by the median urinary iodine concentration (UIC). World Health Organization, the United Nations Childrens Fund, and the International Council for Iodine Deficiency Disorders have established that a median of UIC between 150 and 249u2009μg/L in pregnant women indicates an adequate iodine intake. The aim of this study was to assess iodine nutrition status in Mexican pregnant women.nnnMETHODSnTwo hundred ninety-four pregnant women receiving prenatal care in the Public Medical Units of the State Ministry of Health for each pregnancy trimester (first, n=60; second, n=103; and third, n=131) in Queretaro, Mexico, were enrolled to assess UIC by the Sandell-Kholtoff method.nnnRESULTSnThe median of UIC was 273, 285, and 231u2009μg/L in the first, second, and third trimesters of gestation, respectively. Globally, the median (range) of UIC was 260 (5-1320) μg/L, and the percentage of samples with UIC below 150u2009μg/L was 28%. There was no significant difference between the UIC of women using iodine-containing multivitamins compared with those who reported the consumption of noniodized multivitamins (p>0.05). In addition, we found no difference between the UIC of women using iodized table salt compared with those who employed noniodized table salt, with those who did not know whether their table salt was iodized (p>0.05).nnnCONCLUSIONSnBased on the median UIC, iodine intake in Queretaro, Mexico, is slightly above requirements during the first two trimesters, and adequate in the third trimester. The wide Mexican universal iodized salt program seems to supply adequate dietary iodine to pregnant women without health insurance in this region. However, regular monitoring of iodine status is recommended during pregnancy throughout Mexico.

MCF-7 breast carcinoma cells express ryanodine receptor type 1: functional characterization and subcellular localization

Breast carcinoma-derived MCF-7 cells are frequently used in biomedical research. However, few reports exist regarding the characterization of signaling mechanisms in these cancerous cells involved in intracellular Ca2+ dynamics. Consequently, the aim of these experiments was to characterize the ryanodine receptor/Ca2+ release channel (RyR) present in MCF-7 cells. Ryanodine (100xa0nM), cADPR (5xa0μM), and caffeine (10xa0mM) promoted cytoplasmic Ca2+ mobilization; in contrast, ryanodine at inhibitory concentration (100xa0μM) decreased the basal Ca2+ level. Fluorescent probes demonstrated that RyR is located mainly in endomembranes. Some degree of co-localization with inositol trisphosphate receptor (IP3R) was observed, whereas coincidence with thapsigargin-sensitive Ca2+-ATPase (SERCA) was more limited. Molecular cloning resulted in the detection exclusively of RyR isoform 1. For the first time, it is shown that MCF-7 cells express functional RyR.