A complex between 6-iodolactone and the peroxisome proliferator-activated receptor type gamma may mediate the antineoplasic effect of iodine in mammary cancer

Núñez-Anita, Rosa Elvira; Arroyo-Helguera, Omar; Cajero-Juárez, Marcos; López-Bojórquez, Lucia Nikolaia; Aceves, Carmen

doi:10.1016/j.prostaglandins.2009.04.001

Cited by 33 publications

(41 citation statements)

References 39 publications

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“…In relation to molecular mechanisms, our results showed that iodine induces significant expression of PPARg in DMBA-treated mammary glands and frank tumors, but not in normal mammary gland, and that this increase correlates with the activation of caspase-3 and the induction of DNA rupture (TUNEL), suggesting that PPARg could be a crucial mediator of the antineoplastic iodine effect. These results agree with our previous data showing that the apoptotic effect of iodine or 6-IL is accompanied by the significant induction of PPARg in both in vitro and in vivo models , Nuñez-Anita et al 2009) and that 6-IL is a specific activator ligand of this receptor (Nuñez-Anita et al 2009). Moreover, a recent report shows that pretreatment with rosiglitazone -a potent agonist of PPARg -synergizes the anticancer activity of cisplatin and minimizes cisplatin-induced nephrotoxicity by stimulating PPARg expression in DMBAinduced tumors (Tikoo et al 2009).…”

Section: Discussionsupporting

confidence: 93%

“…Data obtained in either in vivo (N-methylnitrosourea (MNU)) or in vitro (the human mammary cancer cell line MCF-7) models of mammary cancer show that I 2 but not I K (KI or NaI) exert an antineoplastic effect by increasing the expression of peroxisome proliferator-activated receptor g (PPARg), which triggers apoptotic mechanisms that include the Bax-caspase and apoptosis-inducing-factor (AIF) pathways (García-Solís et al 2005, Shrivastava et al 2006. Moreover, we recently demonstrated that 6-iodolactone (6-IL), which is generated by the iodination of arachidonic acid (AA), is a specific ligand of PPARg (Nuñez-Anita et al 2009). The finding that I K has no effect in these models has been explained by the absence of the same components required in thyrocytes: NIS for uptake of iodide and/or lactoperoxidase (LPO) for its oxidation.…”

Section: Introductionmentioning

confidence: 99%

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

Soriano

Delgado²,

Anguiano³

et al. 2011

Endocrine-Related Cancer

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Several groups, including ours, have reported that iodine exhibited antiproliferative and apoptotic effects in various cancer cells only if this element is supplemented as molecular iodine, or as iodide, to cells that are able to oxidize it with the enzyme thyroperoxidase. In this study, we analyzed the effect of various concentrations of iodine and/or iodide in the dimethylbenz [a] anthracene (DMBA) mammary cancer model in rats. The results show that 0.1% iodine or iodide increases the expression of peroxisome proliferator-activated receptor type g (PPARg), triggering caspase-mediated apoptosis pathways in damaged mammary tissue (DMBA-treated mammary gland) as well as in frank mammary tumors, but not in normal mammary gland. DMBA treatment induces the expression of lactoperoxidase, which participates in the antineoplastic effect of iodide and could be involved in the pro-neoplastic effect of estrogens, increasing the formation of DNA adducts. In conclusion, our results show that a supplement of 0.1% molecular iodine/potassium iodide (0.05/0.05%) exert antineoplastic effects, preventing estrogen-induced DNA adducts and inducing apoptosis through PPARg/caspases in pre-cancer and cancerous cells. Since this iodine concentration does not modify the cytology (histology, apoptosis rate) or physiology (triiodothyronine and thyrotropin) of the thyroid gland, we propose that it be considered as an adjuvant treatment for premenopausal mammary cancer.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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

Soriano

Delgado²,

Anguiano³

et al. 2011

Endocrine-Related Cancer

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“…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). While in an indirect way iodine can be iodinated fatty acids derived from arachidonic acid and join a superfamily of known nuclear receptors as receptors activators peroxisomal proliferation (PPAR), which have the function of acting as transcription factors that regulate antioxidant genes activation (24)(25)(26). Iodine deficiency may be involved in the alteration of the antioxidant balance, and thus increase levels of oxidative stress, causing the development of complications during pregnancy and hypertensive disorders (5).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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Background: Previously has been reported the antioxidant function of iodine, and iodine deficiency as a risk factor of preeclampsia.Aim: We analyze the association between iodine deficiency, oxidative stress and antioxidant status with hypertensive disease of pregnancy (HPD).Method: 57 pregnant women were recruited in the last trimester of pregnancy, 20 diagnosed with hypertensive disease of pregnancy and 37 normotensive pregnant women. Urinary iodine concentration (UIC), TSH, free T4 (fT4), total antioxidant status (FRP), Superoxide dismutase (SOD), Catalase (CAT), and oxidative stress (TBARS) were evaluated by colorimetric methods.Results: UIC median for all pregnant women was of 151.9 µg / L. The UIC median for pregnant women with HPD was between 50-149 µg/L compared to 150-249 µg/L in normotensive women. No significant changes were found in levels of TSH and fT4 in normotensive pregnant compared with HPD women. Pregnant women with HPD had significant high levels of TBARS, and significant low levels of FRP, SOD, CAT and UIC compared to normotensive pregnant. In addition, pregnant women with optimal levels of UIC had a higher SOD activity (R = 0.354, P = 0.011), while iodine deficiency was associated with HPD (R = -0,281, p = 0.039). Similarly, pregnant with HPD had a significant negative association with SOD activity (R = -0,702, p = 0.005), CAT (R = -0,409, p = 0.002), and FRP (R = -0,624, p = 0.003), and a positive association with TBARS (R = 0.744, p = 0.001).Conclusion: iodine contributes to REDOX balance during pregnancy; its deficiency is associated with HPD. This study shows the importance of iodine during pregnancy.

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“…In extrathyroid tissues, iodine plays an important role in the redox balance, either by free radical competition or indirectly inducing antioxidant enzymes, mediated by PPAR-gamma transcription factor activated by iodolactones. This ligand has been reported as iodine mediator [12,13,15,16,20,21]. Adequate iodine supplement is important for normal pregnancy, as iodine deficiency has been associated with oxidative stress and pregnant complications such as preeclampsia [22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Iodine Affects Differentiation and Migration Process in Trophoblastic Cells

Vidal

Rodríguez

Arroyo-Helguera

2015

Biol Trace Elem Res

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Iodine deficiency is associated with oxidative stress increase and preeclampsia during gestation, suggesting that iodine concentration plays an important role in the normal placenta physiology. The question raised is to analyze the effect of iodine deficiency on oxidative stress, viability, differentiation, and migration process and changes in the expression of differentiation and migration markers. Iodine deprivation was done using potassium perchlorate (KCLO4) to block sodium iodide symporter (NIS) transporter and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid DIDS to inhibit pendrine (PEN) transport for 3-48 h. Then trophoblast cells were treated with low iodine doses of 5-500 μM and high iodine doses of 100-5000 μM. Oxidative stress, viability, and human chorionic gonadotropin (hGC) were measured by colorimetric methods. Migration throphoblast cells were evaluated by both wound healing and Boyden chamber assays. Changes in mRNA expression were analyzed by real-time RT-PCR. Iodine deprivation induces a significant increase of reactive oxygen species (ROS), viability, and migration process vs control cells. We found a significant overregulation in the mRNA's peroxisome proliferator-activated receptor (PPAR-gamma), Snail, and matrix metalloproteinase-9 (MMP-9) mRNA's in cells deprived of iodine, as well as a down glial cell missing-1 (GCM-1) regulation, hGC, pregnancy-associated plasma protein-A (PAPP-A), and E-cadherin mRNA expression. The expression of hypoxic induction factor alpha (HIFα) mRNA does not change with iodine deprivation. In cells deprived of iodine, supplementing low iodine doses (5-500 μM) does not induce any significant changes in viability. However, ROS and migration process were decreased, although we found an increased human chorionic gonadotropin (hCG) secretion as a differentiation marker. In addition, we found that PPAR-gamma, Snail, and MPP-9 mRNAs expression are downregulated with low iodine doses, in contrast with GCM-1, PAPP-A, hGC, and E-cadherin that increase their expression vs cells deprived of iodine. High iodine doses (1000-5000 μM) have shown cytotoxic effects. Based on our results, iodine is important for keeping the proliferation/differentiation balance in the placenta.

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A complex between 6-iodolactone and the peroxisome proliferator-activated receptor type gamma may mediate the antineoplasic effect of iodine in mammary cancer

Cited by 33 publications

References 39 publications

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

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

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

Iodine Affects Differentiation and Migration Process in Trophoblastic Cells

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