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

Arroyo-Helguera, Omar; Rojas, Emilio; Delgado, Gabriela; Aceves, Carmen

doi:10.1677/erc-08-0125

Cited by 45 publications

(53 citation statements)

References 37 publications

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“…The presence of LPO in pregnant and lactating mammary glands is considered to be an adaptive mechanism to ensure an adequate supply of iodine to the neonate (Memphan 1987). This enzyme has been reported to be present at a very low concentration or even absent in non-lactating mammary glands and in some tumor cell models such as MNU tumors or MCF-7 and MDA-MD231 cells (Anguiano et al 2007, Arroyo-Helguera et al 2008; however, the present data show that LPO is expressed in precancerous and cancerous DMBA-treated mammary cells. Furthermore, preliminary data from our laboratory demonstrate the presence of LPO in samples of early and advanced human breast cancer (unpublished data).…”

Section: Discussioncontrasting

confidence: 81%

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: Discussioncontrasting

confidence: 81%

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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“…KJ was found to have no effect, but at high concentrations enhances the antiproliferative/cytotoxic effect of molecular iodine. Although the mechanisms of action were not analysed here, it is most likely that mitochondrial-mediated apoptosis pathways are involved as previously described for I 2 and iodolactones (6,(9)(10)(11)(12)(13).…”

Section: Discussionmentioning

confidence: 99%

Antiproliferative/cytotoxic effects of molecular iodine, povidone-iodine and Lugol's solution in different human carcinoma cell lines

et al. 2016

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Abstract. Clinical trials have revealed that molecular iodine (I 2 ) has beneficial effects in fibrocystic breast disease and in cyclic mastalgia. Likewise, povidone-iodine (PVP-I), which is widely used in clinical practice as an antiseptic agent following tumour surgery, has been demonstrated to have cytotoxic effects on colon cancer and ascites tumour cells. Our previous study indicated that the growth of breast cancer and seven other human malignant cell lines was variably diminished by I 2 and iodolactones. With the intention of developing an iodine-based anticancer therapy, the present investigations extended these studies by comparing the cytotoxic capacities of I 2 , potassium iodide (KJ), PVP-I and Lugol's solution on various human carcinoma cell lines. Upon staining the cell nuclei with Hoechst 33342, the cell densities were determined microscopically. While KJ alone did not affect cell proliferation, it enhanced the antiproliferative activity of I 2 . In addition, PVP-I significantly inhibited the proliferation of human MCF-7 breast carcinoma, IPC melanoma, and A549 and H1299 lung carcinoma cells in a concentration corresponding to 20 µM I 2 . Likewise, Lugol's solution in concentrations corresponding to 20-80 µM I 2 were observed to reduce the growth of MCF-7 cells. Experiments with fresh human blood samples revealed that the antiproliferative activity of PVP-I and I 2 is preserved in blood plasma to a high degree. These findings suggest that PVP-I, Lugol's solution, and a combination of iodide and I 2 may be potent agents for use in the development of antitumour strategies.

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“…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).…”

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

Cited by 45 publications

References 37 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

Antiproliferative/cytotoxic effects of molecular iodine, povidone-iodine and Lugol's solution in different human carcinoma cell lines

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

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