Iodine Articles 13

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Iodine. Monograph.
            (2010) Download
Iodine is a non-metallic element discovered by French chemist, Bernard Courtois, in 1811. Its name is derived from the Greek “iodes” meaning violet or purple, the color of iodine in its gaseous phase. An essential trace mineral in humans, iodine is necessary for the synthesis of thyroid hormones. In addition, iodine plays a significant role in maintaining breast health. Furthermore, animal studies suggest iodine may possibly benefit adrenal and immune function.6,7 Dietary sources of iodine include iodized salt, seafood, seaweed, cow’s milk, navy beans, and potatoes.

Iodine and doxorubicin, a good combination for mammary cancer treatment: antineoplastic adjuvancy, chemoresistance inhibition, and cardioprotection.
            (Alfaro et al., 2013) Download
BACKGROUND:  Although mammary cancer (MC) is the most common malignant neoplasia in women, the mortality for this cancer has decreased principally because of early detection and the use of neoadjuvant chemotherapy. Of several preparations that cause MC regression, doxorubicin (DOX) is the most active, first-line monotherapeutic. Nevertheless, its use is limited due to the rapid development of chemoresistance and to the cardiotoxicity caused by free radicals. In previous studies we have shown that supplementation with molecular iodine (I2) has a powerful antineoplastic effect in methylnitrosourea (MNU)-induced experimental models of MC. These studies also showed a consistent antioxidant effect of I2 in normal and tumoral tissues. METHODS:  Here, we analyzed the effect of I2 in combination with DOX treatment in female Sprague Dawley rats with MNU-induced MC. In the first experiment (short) animals were treated with the therapeutic DOX dose (16 mg/kg) or with lower doses (8 and 4 mg/Kg), in each case with and without 0.05% I2 in drinking water. Iodine treatment began on day 0, a single dose of DOX was injected (ip) on day 2, and the analysis was carried out on day 7. In the second experiment (long) animals with and without iodine supplement were treated with one or two injections of 4 mg/kg DOX (on days 0 and 14) and were analyzed on day 56. RESULTS:  At all DOX doses, the short I2 treatment induced adjuvant antineoplastic effects (decreased tumor size and proliferating cell nuclear antigen level) with significant protection against body weight loss and cardiotoxicity (creatine kinase MB, cardiac lipoperoxidation, and heart damage). With long-term I2, mammary tumor tissue became more sensitive to DOX, since a single injection of the lowest dose of DOX (4 mg/Kg) was enough to stop tumor progression and a second DOX4 injection on day 14 caused a significant and rapid decrease in tumor size, decreased the expression of chemoresistance markers (Bcl2 and survivin), and increased the expression of the apoptotic protein Bax and peroxisome proliferator-activated receptor type gamma. CONCLUSIONS:  The DOX-I2 combination exerts antineoplastic, chemosensitivity, and cardioprotective effects and could be a promising strategy against breast cancer progression.

The potential of iodine for improving breast cancer diagnosis and treatment.
            (Altman et al., 2013) Download
Early detection through modalities such as mammography remains pivotal in the fight against breast cancer. The detectability of breast cancer through mammography is rooted in the differential X-ray attenuation properties of cancerous and normal breast tissue. An unexplored component of the X-ray contrast between fibrous breast tissue and similarly composed tumor tissue is the presence of naturally localized iodine in the cancer but not healthy breast tissue. It is hypothesized that differing amounts of iodine are present in tumor versus normal breast tissue that leads to more easily detectable cancer due to an increased Z value of the tumor tissue relative to the healthy tissue, which results in enhanced differences in X-ray attenuation properties between the two tissues and thus greater radiographic contrast. The hypothesis is supported by experimental observations explaining how iodine could localize in the tumor tissue but not surrounding healthy tissue. Breast cancer cells express the sodium-iodide symporter (NIS), an ion pump which sequesters iodine in tumor cells. Healthy non-lactating breast tissue, in contrast, does not express NIS. Further evidence for the differential expression of NIS resulting in X-ray contrast enhancement in breast cancer is the established correlation between expression of insulin growth factor (IGF) and enhanced X-ray contrast, and the evidence that IGF is a promoter for NIS. Ultimately, if the expression of iodine can be shown to be a component of radiographic contrast between healthy and tumor breast tissue, this could be used to drive the development of new technology and techniques for use in the detection and treatment of breast cancer. The proof of this hypothesis could thus have a substantial impact in the fight against breast cancer.

The influence of estrogen upon goiter induction in adult and immature rats.
            (Bogdanove and Eskin, 1956) Download
There have been many conflicting reports as to the way in which the thyroid glands of experimental animals are affected, if at all, by the administration of "estrogenic hormones. The subject has been carefully reviewed by Noach (1, 2). In adult, propylthiouracil-treated rats, we have found that the concurrent administration of an estrogen, a-estradiol 2 benzoate , reduces the hyperplastic response of the thyroid gland to the goitrogen. The present report deals with this inhibitory phenomenon, and with the effects thereon of age, sex, strain and variations in drug dosage.

Iodine metabolism and breast cancer
            (Eskin, 1970)  Download
Statistics favor an increased rate of breast cancer morbidity in regions of known endemic goiter. Demographic surveys of Japan and Iceland show low incidences of endemic nontoxic goiter and breast cancer, while Mexico and Thailand show high incidences of goiter and breast cancer. In addition, increased breast cancer in specific endemic-goiter regions in Poland, Switzerland, Australia, and the Soviet Union have been described in publications and through personal communications.

Sex hormones and aging.
            (Eskin, 1978) Download
Many medications have been suggested which may diminish the effects of aging on various tissues in the body. Particularly notable have been the interventions into the characteristic changes involving the skin, sensory, cardiovascular and neurologic systems, all of which have been considered to abrogate the declining intracellular metabolic maintenance. Intervention by the use of sex hormones is more definitive and serves multiple systems. The hormones have peripheral somatic action but the major known responses deal with primary and secondary sexual tissues.

Iodine and cancer.
            (Feldt-Rasmussen, 2001) Download
Thyroid carcinomas are the most frequent endocrine malignancies. Among thyroid carcinomas the most frequent types are the differentiated forms (follicular, papillary or mixed papillary-follicular), whereas anaplastic thyroid carcinoma and medullary thyroid carcinomas are rare. Animal experiments have demonstrated a clear increase in incidence of thyroid epithelial cell carcinomas after prolonged iodine deficiency leading to a situation of the thyroid gland by thyrotropin and possibly other growth factors. However, the overall incidence of differentiated thyroid carcinoma is generally not considered to be influenced by the iodine intake of a population, whereas the distribution of the types of thyroid carcinoma seems to be related to the intake of iodine, with fewer of the more aggressive follicular and anaplastic carcinomas and more papillary carcinomas in iodine rich areas. Populations starting iodine prophylaxis demonstrate an increase in the ratio of papillary to follicular carcinoma. Because a population with higher iodine intake usually has fewer benign nodules in the thyroid gland and the incidence of thyroid carcinomas is similar to an iodine-deficient region, the diagnostic work-up of nodules in the thyroid gland may become affected. The incidence of other cancers, such as breast cancer, may be influenced by the iodine intake, but too few studies are available at present. The present article summarizes available data from both epidemiological studies, animal experiments, and basic gene transfection studies. The overall incidence for a relationship between iodine and cancer is poor and future studies are warranted.

Urinary Iodine Concentrations in Cancer Patients
            (Kargar et al., 2017) Download
Background: It has been suggested that incidence of some cancers, especially examples in the breast and stomach may be influenced by the iodine intake. However, only few studies are available at present. Therefore, we have conducted the present assessment of iodine status in Iranian patients diagnosed with a malignancy. Materials and Methods: This cross-sectional study was conducted in 85 patients diagnosed with different types of cancer at Shahid Sadoughi Hospital, Yazd, Iran. The method used was based on the Sandell–Kolthoff reaction. Results: The median urinary iodine concentration (UIC) was 17.4 μg/L, with ≤20 μg/L indicative of severe iodine deficiency. According to the WHO/IC C

The correlation between breast cancer and urinary iodine excretion levels.
            (Malya et al., 2018) Download
Objective To compare urinary iodine excretion levels in patients with breast cancer and control subjects. Methods In this prospective pilot study, patients with breast cancer and normal controls were recruited. Age and menopausal status were recorded. Levels of serum thyroid-stimulating hormone, blood urea nitrogen and creatinine and urine iodine concentration (UIC) were measured. UIC levels were divided into three categories: low (<100 µg/l), normal (100-200 µg/l) or high (>200 µg/l). Results A total of 24 patients with breast cancer and 48 controls were included in the study. There were no statistically significant differences between the two groups with regard to thyroid-stimulating hormone, blood urea nitrogen or creatinine levels. When considered overall, there was no statistical difference in UIC between patients and controls. However, comparisons within each category (low, normal or high UIC) showed a significantly higher percentage of patients with breast cancer had a high UIC compared with controls. Conclusions A high UIC was seen in a significantly higher percentage of patients with breast cancer than controls. UIC may have a role as a marker for breast cancer screening. Further studies evaluating UIC and iodine utilization in patients with breast cancer are warranted.


 

Enhanced tight junction function in human breast cancer cells by antioxidant, selenium and polyunsaturated lipid.
            (Martin et al., 2007) Download
Paracellular permeability (PCP) is governed by tight junctions (TJs) in epithelial cells, acting as cell-cell adhesion structures, the aberration of which is known to be linked to the dissociation and metastasis of breast cancer cells. This study hypothesized that the function of TJs in human breast cancer cells can be augmented by gamma linolenic acid (GLA), selenium (Se), and iodine (I) in the presence of 17-beta-estradiol, as these molecules are known to increase TJ functions in endothelial cells, using assays of trans-epithelial resistance (TER), PCP, immunofluorescence, and in vitro invasion and motility models. GLA, I, and Se individually increased TER of MDA-MB-231 and MCF-7 human breast cancer cells. The combination of all three agents also had a significant increase in TER. Addition of GLA/Se/I reduced PCP of both breast cancer cell lines. GLA/Se/I reversed the effect of 17-beta-estradiol (reduced TER, increased PCP). Immunofluorescence revealed that after treatment with Se/I/GLA over 24 h, there was increasing relocation to breast cancer cell-cell junctions of occludin and ZO-1 in MCF-7 cells. Moreover, treatment with GLA/Se/I, alone or in combination, significantly reduced in vitro invasion of MDA-MB-231 cells through an endothelial cell barrier (P < 0.0001) and reduced 17-beta-estradiol induced breast cancer cell motility (P < 0.0001). Our previous work has demonstrated that GLA, I, and Se alone, or in combination are able to strengthen the function of TJs in human endothelial cells; this has now proved to be true of human breast cancer cells. This combination also completely reversed the effect of 17-beta-estradiol in these cells.

Evaluation of postpartum breast engorgement by thermography.
            (Menczer and Eskin, 1969) Download
Initial postpartum breast discomfort is assumed to be caused primarily by venous engorgement. This study evaulated venous engorgement of the breast by thermography.

Iodide transport and breast cancer.
            (Poole and McCabe, 2015) Download
Breast cancer is the second most common cancer worldwide and the leading cause of cancer death in women, with incidence rates that continue to rise. The heterogeneity of the disease makes breast cancer exceptionally difficult to treat, particularly for those patients with triple-negative disease. To address the therapeutic complexity of these tumours, new strategies for diagnosis and treatment are urgently required. The ability of lactating and malignant breast cells to uptake and transport iodide has led to the hypothesis that radioiodide therapy could be a potentially viable treatment for many breast cancer patients. Understanding how iodide is transported, and the factors regulating the expression and function of the proteins responsible for iodide transport, is critical for translating this hypothesis into reality. This review covers the three known iodide transporters - the sodium iodide symporter, pendrin and the sodium-coupled monocarboxylate transporter - and their role in iodide transport in breast cells, along with efforts to manipulate them to increase the potential for radioiodide therapy as a treatment for breast cancer.

Changes in Dietary Iodine Explains Increasing Incidence of Breast Cancer with Distant Involvement in Young Women.
            (Rappaport, 2017) Download
The hypothesis that iodine deficiency in the United States, plays a role in the increased incidence of breast cancer with distant involvement, is discussed here in the context of these three factors.

Zoledronate and Molecular Iodine Cause Synergistic Cell Death in Triple Negative Breast Cancer through Endoplasmic Reticulum Stress.
            (Tripathi et al., 2016) Download
Women consuming molecular iodine (I2) through seaweeds suffer the least from breast cancers. Zoledronate (Zol) is in clinical use for alleviation of bone pain in cancer patients. Triple negative breast cancers exhibit high mortality due to lack of neoadjuvant chemotherapy. I2 and Zol independently cause weak antiproliferative and apoptotic effect. So far, their combined effects have not been tested. We analyzed the effect of combination of I2 with Zol as a potent adjuvant therapeutic agent for triple negative breast cancer cells (MDA-MBA-231) and in the mice model of breast cancer. Cell viability, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, Western blotting, real-time PCR, flow cytometry, and other assays were performed for assessing cell death, calcium levels, and migration potential, respectively, in treated cells. The increased caspase 8, increased [Ca(2+)]c levels, and endoplasmic reticulum (ER) stress resulted in apoptosis. Real time and fluorescence-based analysis demonstrated that the combination treatment targets ER Ca(2+) homeostasis chaperons leading to apoptosis. Combination therapy reduces metalloproteinases 2 and 9, inhibits invasion/migration of cells, and prevents growth of tumor in mice. I2 + Zol combination treatment induces synergistic increase in ER-mediated apoptosis, reduces invasion/migration potential of MDA-MB-231 cells, and exhibits antiproliferative property in vivo demonstrating its potential as combination therapy.

 


References

Alfaro, Y, et al. (2013), ‘Iodine and doxorubicin, a good combination for mammary cancer treatment: antineoplastic adjuvancy, chemoresistance inhibition, and cardioprotection.’, Mol Cancer, 12 45. PubMed: 23705792
Altman, MB, et al. (2013), ‘The potential of iodine for improving breast cancer diagnosis and treatment.’, Med Hypotheses, 80 (1), 94-98. PubMed: 23171625
Bogdanove, EM and BA Eskin (1956), ‘The influence of estrogen upon goiter induction in adult and immature rats.’, Endocrinology, 59 (6), 688-94. PubMed: 13375595
Eskin, BA (1970), ‘Iodine metabolism and breast cancer’, Trans N Y Acad Sci, 32 (8), 911-47. PubMed: 5279909
——— (1978), ‘Sex hormones and aging.’, Adv Exp Med Biol, 97 207-24. PubMed: 347900
Feldt-Rasmussen, U (2001), ‘Iodine and cancer.’, Thyroid, 11 (5), 483-86. PubMed: 11396706
(2010), ‘Iodine. Monograph.’, Altern Med Rev, 15 (3), 273-78. PubMed: 21155628
Kargar, S, et al. (2017), ‘Urinary Iodine Concentrations in Cancer Patients’, Asian Pac J Cancer Prev, 18 (3), 819-21. PubMed: 28441792
Malya, FU, et al. (2018), ‘The correlation between breast cancer and urinary iodine excretion levels.’, J Int Med Res, 46 (2), 687-92. PubMed: 28856936
Martin, TA, et al. (2007), ‘Enhanced tight junction function in human breast cancer cells by antioxidant, selenium and polyunsaturated lipid.’, J Cell Biochem, 101 (1), 155-66. PubMed: 17243118
Menczer, J and BA Eskin (1969), ‘Evaluation of postpartum breast engorgement by thermography.’, Obstet Gynecol, 33 (2), 260-63. PubMed: 4886952
Poole, VL and CJ McCabe (2015), ‘Iodide transport and breast cancer.’, J Endocrinol, 227 (1), R1-R12. PubMed: 26285906
Rappaport, J (2017), ‘Changes in Dietary Iodine Explains Increasing Incidence of Breast Cancer with Distant Involvement in Young Women.’, J Cancer, 8 (2), 174-77. PubMed: 28243321
Tripathi, R, et al. (2016), ‘Zoledronate and Molecular Iodine Cause Synergistic Cell Death in Triple Negative Breast Cancer through Endoplasmic Reticulum Stress.’, Nutr Cancer, 68 (4), 679-88. PubMed: 27116040