Pancreatitis has been implicated in the development and progression of type 2 diabetes and cancer... more Pancreatitis has been implicated in the development and progression of type 2 diabetes and cancer. The pancreas uptakes molecular iodine (I2), which has anti-inflammatory and antioxidant effects. The present work analyzes whether oral I2 supplementation prevents the pancreatic alterations promoted by low doses of streptozotocin (STZ). CD1 mice (12 weeks old) were divided into the following groups: control; STZ (20 mg/kg/day, i.p. for five days); I2 (0.2 mg/Kg/day in drinking water for 15 days); and combined (STZ + I2). Inflammation (Masson’s trichrome and periodic acid–Schiff stain), hyperglycemia, decreased β-cells and increased α-cells in pancreas were observed in male and female animals with STZ. These animals also showed pancreatic increases in immune cells and inflammation markers as tumor necrosis factor-alpha, transforming growth factor-beta and inducible nitric oxide synthase with a higher amount of activated pancreatic stellate cells (PSCs). The I2 supplement prevented the ...
Thyroxine (T4) promotes cell proliferation and tumor growth in prostate cancer models, but it is ... more Thyroxine (T4) promotes cell proliferation and tumor growth in prostate cancer models, but it is unknown if the increase in the triiodothyronine (T3)/T4 ratio could attenuate prostate tumor development. We assessed T3 effects on thyroid response, histology, proliferation, and apoptosis in the prostate of wild-type (WT) and TRAMP (transgenic adenocarcinoma of the mouse prostate) mice. Physiological doses of T3 were administered in the drinking water (2.5, 5 and 15 µg/100 g body weight) for 6 weeks. None of the doses modified the body weight or serum levels of testosterone, but all of them reduced serum T4 levels by 50%, and the highest dose increased the T3/T4 ratio in TRAMP. In WT, the highest dose of T3 decreased cyclin D1 levels (immunohistochemistry) but did not modify prostate weight or alter the epithelial morphology. In TRAMP, this dose reduced tumor growth by antiproliferative mechanisms independent of apoptosis, but it did not modify the intraluminal or fibromuscular invasio...
Thyroid hormones (THs) are involved in the development and function of the male reproductive syst... more Thyroid hormones (THs) are involved in the development and function of the male reproductive system, but their effects on the prostate have been poorly studied. This work reviews studies related to the interrelationship between the thyroid and the prostate. The information presented here is based upon bibliographic searches in PubMed using the following search terms: prostate combined with thyroid hormone or triiodothyronine, thyroxine, hypothyroidism, hyperthyroidism, or deiodinase. We identified and searched 49 articles directly related to the issue, and discarded studies related to endocrine disruptors. The number of publications has grown in the last 20 years, considering that one of the first studies was published in 1965. This review provides information based on in vitro studies, murine models, and clinical protocols in patients with thyroid disorders. Studies indicate that THs regulate different aspects of growth, metabolism, and prostate pathology, whose global effect depen...
Iodine and doxorubicin, a good combination for mammary cancer treatment: antineoplastic adjuvancy... more Iodine and doxorubicin, a good combination for mammary cancer treatment: antineoplastic adjuvancy, chemoresistance inhibition, and cardioprotection
International Journal of Cancer Therapy and Oncology, 2015
Purpose: In addition to being a component of thyroid hormone (TH), iodine can be an antioxidant a... more Purpose: In addition to being a component of thyroid hormone (TH), iodine can be an antioxidant as well as an antiproliferative and differentiation agent that helps to maintain the integrity of several organs with the ability to take up iodine. Methods and Results : Studies from our laboratory shown that in preclinical (cell culture, induced animal cancer and xenographs) and clinical studies (mammary cancer protocol), molecular iodine (I 2 ) supplementation exerts suppressive effects on implantation, development, and progression of cancer neoplasias. These effects can be mediated by a variety of mechanisms and pathways, including direct actions, in which the oxidized iodine modulates the immune/tumor response and through iodolipid formation and the activation of peroxisome proliferator-activated receptors type gamma (PPARγ) triggering apoptotic and/or differentiation pathways. Conclusion: The absence of side effects and the easy availability and handling of I 2 have allowed the esta...
Neuroblastoma (NB) is the most common solid childhood tumor, and all-trans retinoic acid (ATRA) i... more Neuroblastoma (NB) is the most common solid childhood tumor, and all-trans retinoic acid (ATRA) is used as a treatment to decrease minimal residual disease. Molecular iodine (I2) induces differentiation and/or apoptosis in several neoplastic cells through activation of PPARγ nuclear receptors. Here, we analyzed whether the coadministration of I2 and ATRA increases the efficacy of NB treatment. ATRA-sensitive (SH-SY5Y), partially-sensitive (SK-N-BE(2)), and non-sensitive (SK-N-AS) NB cells were used to analyze the effect of I2 and ATRA in vitro and in xenografts (Foxn1 nu/nu mice), exploring actions on cellular viability, differentiation, and molecular responses. In the SH-SY5Y cells, 200 μM I2 caused a 100-fold (0.01 µM) reduction in the antiproliferative dose of ATRA and promoted neurite extension and neural marker expression (tyrosine hydroxylase (TH) and tyrosine kinase receptor alpha (Trk-A)). In SK-N-AS, the I2 supplement sensitized these cells to 0.1 μM ATRA, increasing the AT...
We evaluated the effect of oral molecular iodine supplementation and shock wave application under... more We evaluated the effect of oral molecular iodine supplementation and shock wave application under three different conditions on human MDA-MB231 cancer cell xenografts. After tumor volume reached 1 cm 3 , mice were randomly assigned to groups and treated for 3 weeks. The results revealed that high-dose shock wave treatment (150 shock waves at a pressure of 21.7 MPa, SW150/21.7) generated tissue lesions without decreasing tumor growth, canceled the antineoplastic action of iodine and promoted pro-tumor conditions (increased hypoxia-induced factor [HIF] and vascular endothelial growth factor [VEGF]). In contrast, moderate (SW35/21.7) and low (SW35/9.9) doses of shock waves had significant antineoplastic effects and, in combination with iodine supplement, attenuated the aggressiveness of these cells by decreasing expression of the markers of stem cells (CD44 and Sox2) and invasion (HIF and VEGF). These results allow us to propose the combination of shock waves and iodine as a possible adjuvant in breast cancer therapy.
The present work analyzes the antineoplastic effects of molecular iodine alone and in combination... more The present work analyzes the antineoplastic effects of molecular iodine alone and in combination with the neoadjuvant therapy FEC/TE (5-fluorouracil/epirubicin/cyclophosphamide or taxotere/epirubicin) in women with breast cancer. In this protocol the immunohistochemistry methodology for the quantification of the estrogen receptor and the proteins associated with the installation of the mesenchymal epithelium transition (e-cadherin and vimentin), immune response (CD8) and cell death (TUNEL) is described, and the methodology for transcriptomic analyses includes: RNA-Seq and transcriptomic analysis; pathway enrichment analysis; validation of the immune response and epithelium/stroma rate and, prediction of the transcription factor regulatory network and peroxisome proliferator-activated receptors type gamma (PPARg) interaction
This study analyzes oral supplement of molecular iodine (I2) alone and in combination with the ne... more This study analyzes oral supplement of molecular iodine (I2) alone and in combination with the neoadjuvant therapy 5-fluorouracil/epirubicin/cyclophosphamide or taxotere/epirubicin (FEC/TE) in women with Early (stage II) and Advanced (stage III) breast cancer. In the Early group, 30 women were treated with I2 (5 mg/day) or placebo (colored water) for 7–35 days before surgery. For the Advanced group, 30 patients received I2 or placebo along with FEC/TE treatment. After surgery, all patients received FEC/TE + I2 for 170 days. I2 supplementation showed a significant attenuation of the side effects and absence of tumor chemoresistance. Control, I2, FEC/TE, and FEC/TE+I2 groups exhibit response rate of 0, 33%, 73%, and 100%, respectively, and a pathologic complete response of 18%, and 36% in the last two groups. Five-year disease-free survival rate was significantly higher in patients with I2 supplement before and after surgery compared to those receiving the supplement only after surger...
Background: Cancer stem cells (CSC) are characterized by deregulated self-renewal, tumorigenicity... more Background: Cancer stem cells (CSC) are characterized by deregulated self-renewal, tumorigenicity, metastatic potential, aberrant stemness signaling pathways, resistance to conventional therapy, and the ability to give rise to a progeny of proliferating cells that constitute the bulk of tumors. Targeting CSC will provide novel treatments for cancer. Different investigations have focused on developing complementary approaches that involve natural compounds that decrease chemo-resistance and reduce the side effects of conventional therapies. Since, it has been reported that molecular iodine (I 2) exhibits antineoplastic effects and decreases tumor progression in some cancer models, we evaluated the potential effect of I 2 on cell cultures enriched in cervical cancer stem-like cells. Methods: HeLa and SiHa cervical cancer cells were treated with 200uM I 2 for 24 h. After time, cells were cultured in CSC-conditioned medium (cervospheres) and viability assays were performed. Following, tumorigenic capabilities in cervospheres treated with I 2 were evaluated in NOD/SCID mice. HeLa monolayer cells untreated and their respective cervosphere cells treated or untreated with 200 μM of I 2 for 24 h were xenotransplanted subcutaneously at different amounts and mice were monitored for at least 2 months. Results: In the present study, monolayer and CSC-enriched cultures (cervospheres) from cervical cancer-derived cell lines, HeLa and SiHa, showed that 200uM I 2 supplementation inhibits proliferation of both and decreased their tumorigenic capacity, in vivo. This antineoplastic effect of I 2 was accompanied by diminished expression of stemness markers including CD49f, CK17, OCT-4, NANOG, SOX2, and KLF4, as well as increased expression and activation of PPARγ receptors. Conclusions: All this data led us to suggest a clinical potential use of I 2 for targeting CSC and improve current treatments against cervical cancer.
Oxidative stress and inflammation are involved in the development and/or progression of benign pr... more Oxidative stress and inflammation are involved in the development and/or progression of benign prostatic hyperplasia (BPH). Molecular iodine (I2) induces antiproliferative and apoptotic effects in prostate cancer cells, but it is unknown if I2 regulates oxidative stress in the normal and/or tumoral prostate. The purpose of this study was to analyze the effects of I2 and celecoxib (Cxb) on oxidative stress and inflammation in a model of prostatic hyperplasia. Cxb was used as positive control of cyclooxygenase-2 (COX-2) inhibition. Prostatic hyperplasia was induced in male Wistar rats (170g) with testosterone (5mg/kg/week, for three weeks). One week before hyperplasia induction, I2 (25mg/day/rat) or Cxb (1.25mg/day/rat) was supplied for four weeks in the drinking water. Prostatic hyperplasia was evaluated by histological analysis, DNA content, and/or proliferating cell nuclear antigen (PCNA) expression. Lipoperoxidation (malondialdehyde) and nitrite (NO2-) levels were analyzed by colo...
The original version of this article unfortunately contained a mistake. The lable in Fig. 4a, b w... more The original version of this article unfortunately contained a mistake. The lable in Fig. 4a, b was incorrect in the published version of the article. The scale bar has the label ''50 microseconds'' instead of ''50 micrometers''. The corrected Fig. 4 is given below.
Shock waves are known to permeabilize eukaryotic cell membranes, which may be a powerful tool for... more Shock waves are known to permeabilize eukaryotic cell membranes, which may be a powerful tool for a variety of drug delivery applications. However, the mechanisms involved in shock wave-mediated membrane permeabilization are still poorly understood. In this study, the effects on both the permeability and the ultrastructural features of two human cell lineages were investigated after the application of underwater shock waves in vitro. Scanning Electron Microscopy of cells derived from a human embryo kidney (HEK)-293 and Michigan Cancer Foundation (MCF)-7 cells, an immortalized culture derived from human breast adenocarcinoma, showed a small amount of microvilli (as compared to control cells), the presence of hole-like structures, and a decrease in cell size after shock wave exposure. Interestingly, these effects were accompanied by the permeabilization of acid and macromolecular dyes and gene transfection. Trypan blue exclusion assays indicated that cell membranes were porated during...
Archivos Latinoamericanos De Nutricion, Sep 1, 2005
Breast cancer is the most common worldwide neoplasia in women. The totality of etiology factors o... more Breast cancer is the most common worldwide neoplasia in women. The totality of etiology factors of breast cancer is unknown and thus an effective preventive strategy has not been developed. Risk factors associated to breast cancer can be grouped into three broad categories: a) family history (hereditary) factors, b) endocrine and reproductive factors and c) environmental and life-style factors including diet. Animal models of chemical induced mammary carcinogenesis with 7, 12-dimethylbenz[a]anthracene and N-methyl-N-nitrosourea have been useful in the study of biology, treatment and prevention of breast cancer. In this review we show the usefulness and advantages of animal models in the study of nutritional factors associated with breast cancer in order to propose new prevention strategies. We review briefly different experimental approaches as well as some physiologic effects and mechanisms of some nutritional factors studied with animal models of mammary carcinogenesis. Nutritional factors reviewed were: a) energy restriction and high-fat intake, b) soy and phytoestrogens, c) retinoids and carotenoids, d) conjugated linoleic acid, and e) brown seaweed and iodine.
Molecular medicine (Cambridge, Mass.), Jan 26, 2016
Prostate cancer cells are responsive to adrenergic and thyroid stimuli. It is well established th... more Prostate cancer cells are responsive to adrenergic and thyroid stimuli. It is well established that β-adrenergic activation (PKA/CREB) promotes cancer progression, but the role of thyroid hormones (TH) is poorly understood. We analyzed the effects of β-adrenergic stimulation (isoproterenol, ISO), and/or TH on neuroendocrine (NE) differentiation and cell invasion, using in vivo (LNCaP tumor) and in vitro models (LNCaP and DU145 human cells). Nude mice were inoculated with LNCaP cells and were treated for 6 weeks with ISO (200 μg/day), triiodothyronine (T3, 2.5 μg/day), or both. ISO alone reduced tumor growth but increased tumor expression of cAMP response element (CRE)-dependent genes (real-time PCR, chromogranin A, neuron specific enolase, survivin, VEGF, uPA, and MMP-9) and some proteins related to NE differentiation and/or invasiveness (synaptophysin, VEGF, pCREB). T3 reduced tumor growth and prevented the overexpression of ISO-stimulated factors, through a pCREB-independent mecha...
Most investigations of iodine metabolism in humans and animals have focused on its role in thyroi... more Most investigations of iodine metabolism in humans and animals have focused on its role in thyroid function. Public health policies have been established to supply deficient populations with the necessary amount of this element in order to eradicate the iodine deficiency diseases, primarily cretinism. However, considerable evidence indicates that iodine could also be implicated in the physiology of other organs. In humans, the total amount of iodine in the body is 30-50 mg, and less than 30% of it is present in the thyroid gland and its hormones. About 60% of total iodine is non-hormonal and is concentrated in extrathyroidal tissues, where its biological role is still unknown. Moreover, it has been demonstrated that iodine distribution in the organism depends on the chemical form of iodine ingested, and that molecular iodine (I 2) is not totally reduced to iodide (I-) in the blood before it is absorbed systemically from the gastrointestinal tract. Indeed, in iodine deficiency conditions, Iappears to be more efficient than I 2 in restoring the thyroid gland from a goitrous to a normal state, whereas I 2 supplementation diminishes the symptoms of mammary fibrosis in women, causes a 50-70% reduction in the occurrence of mammary cancer induced chemically in rats and exhibit antiproliferative and apoptotic effects in several human tumoral cell lines. Nevertheless, these findings have been viewed with caution, because exposure to moderate or high iodine is thought to be a potential risk to thyroid physiology. Careful examination shows that pathological responses occurred at low or moderate iodine intake in patients with underlying or evident thyroid pathology (e.g. Hashimoto's thyroiditis, history of treated Graves' diseases, etc.); in normal subjects, however, these pathologies occurred only with excessively high doses of iodine or iodide (>20 mg/day). No damaging effects were reported in either the human or animal studies that used therapeutic I 2 concentrations (3 to 15 mg/day). This issue will provide an overview of so-called extrathyroidal iodine, its role, and its potential clinical applications.
Pancreatitis has been implicated in the development and progression of type 2 diabetes and cancer... more Pancreatitis has been implicated in the development and progression of type 2 diabetes and cancer. The pancreas uptakes molecular iodine (I2), which has anti-inflammatory and antioxidant effects. The present work analyzes whether oral I2 supplementation prevents the pancreatic alterations promoted by low doses of streptozotocin (STZ). CD1 mice (12 weeks old) were divided into the following groups: control; STZ (20 mg/kg/day, i.p. for five days); I2 (0.2 mg/Kg/day in drinking water for 15 days); and combined (STZ + I2). Inflammation (Masson’s trichrome and periodic acid–Schiff stain), hyperglycemia, decreased β-cells and increased α-cells in pancreas were observed in male and female animals with STZ. These animals also showed pancreatic increases in immune cells and inflammation markers as tumor necrosis factor-alpha, transforming growth factor-beta and inducible nitric oxide synthase with a higher amount of activated pancreatic stellate cells (PSCs). The I2 supplement prevented the ...
Thyroxine (T4) promotes cell proliferation and tumor growth in prostate cancer models, but it is ... more Thyroxine (T4) promotes cell proliferation and tumor growth in prostate cancer models, but it is unknown if the increase in the triiodothyronine (T3)/T4 ratio could attenuate prostate tumor development. We assessed T3 effects on thyroid response, histology, proliferation, and apoptosis in the prostate of wild-type (WT) and TRAMP (transgenic adenocarcinoma of the mouse prostate) mice. Physiological doses of T3 were administered in the drinking water (2.5, 5 and 15 µg/100 g body weight) for 6 weeks. None of the doses modified the body weight or serum levels of testosterone, but all of them reduced serum T4 levels by 50%, and the highest dose increased the T3/T4 ratio in TRAMP. In WT, the highest dose of T3 decreased cyclin D1 levels (immunohistochemistry) but did not modify prostate weight or alter the epithelial morphology. In TRAMP, this dose reduced tumor growth by antiproliferative mechanisms independent of apoptosis, but it did not modify the intraluminal or fibromuscular invasio...
Thyroid hormones (THs) are involved in the development and function of the male reproductive syst... more Thyroid hormones (THs) are involved in the development and function of the male reproductive system, but their effects on the prostate have been poorly studied. This work reviews studies related to the interrelationship between the thyroid and the prostate. The information presented here is based upon bibliographic searches in PubMed using the following search terms: prostate combined with thyroid hormone or triiodothyronine, thyroxine, hypothyroidism, hyperthyroidism, or deiodinase. We identified and searched 49 articles directly related to the issue, and discarded studies related to endocrine disruptors. The number of publications has grown in the last 20 years, considering that one of the first studies was published in 1965. This review provides information based on in vitro studies, murine models, and clinical protocols in patients with thyroid disorders. Studies indicate that THs regulate different aspects of growth, metabolism, and prostate pathology, whose global effect depen...
Iodine and doxorubicin, a good combination for mammary cancer treatment: antineoplastic adjuvancy... more Iodine and doxorubicin, a good combination for mammary cancer treatment: antineoplastic adjuvancy, chemoresistance inhibition, and cardioprotection
International Journal of Cancer Therapy and Oncology, 2015
Purpose: In addition to being a component of thyroid hormone (TH), iodine can be an antioxidant a... more Purpose: In addition to being a component of thyroid hormone (TH), iodine can be an antioxidant as well as an antiproliferative and differentiation agent that helps to maintain the integrity of several organs with the ability to take up iodine. Methods and Results : Studies from our laboratory shown that in preclinical (cell culture, induced animal cancer and xenographs) and clinical studies (mammary cancer protocol), molecular iodine (I 2 ) supplementation exerts suppressive effects on implantation, development, and progression of cancer neoplasias. These effects can be mediated by a variety of mechanisms and pathways, including direct actions, in which the oxidized iodine modulates the immune/tumor response and through iodolipid formation and the activation of peroxisome proliferator-activated receptors type gamma (PPARγ) triggering apoptotic and/or differentiation pathways. Conclusion: The absence of side effects and the easy availability and handling of I 2 have allowed the esta...
Neuroblastoma (NB) is the most common solid childhood tumor, and all-trans retinoic acid (ATRA) i... more Neuroblastoma (NB) is the most common solid childhood tumor, and all-trans retinoic acid (ATRA) is used as a treatment to decrease minimal residual disease. Molecular iodine (I2) induces differentiation and/or apoptosis in several neoplastic cells through activation of PPARγ nuclear receptors. Here, we analyzed whether the coadministration of I2 and ATRA increases the efficacy of NB treatment. ATRA-sensitive (SH-SY5Y), partially-sensitive (SK-N-BE(2)), and non-sensitive (SK-N-AS) NB cells were used to analyze the effect of I2 and ATRA in vitro and in xenografts (Foxn1 nu/nu mice), exploring actions on cellular viability, differentiation, and molecular responses. In the SH-SY5Y cells, 200 μM I2 caused a 100-fold (0.01 µM) reduction in the antiproliferative dose of ATRA and promoted neurite extension and neural marker expression (tyrosine hydroxylase (TH) and tyrosine kinase receptor alpha (Trk-A)). In SK-N-AS, the I2 supplement sensitized these cells to 0.1 μM ATRA, increasing the AT...
We evaluated the effect of oral molecular iodine supplementation and shock wave application under... more We evaluated the effect of oral molecular iodine supplementation and shock wave application under three different conditions on human MDA-MB231 cancer cell xenografts. After tumor volume reached 1 cm 3 , mice were randomly assigned to groups and treated for 3 weeks. The results revealed that high-dose shock wave treatment (150 shock waves at a pressure of 21.7 MPa, SW150/21.7) generated tissue lesions without decreasing tumor growth, canceled the antineoplastic action of iodine and promoted pro-tumor conditions (increased hypoxia-induced factor [HIF] and vascular endothelial growth factor [VEGF]). In contrast, moderate (SW35/21.7) and low (SW35/9.9) doses of shock waves had significant antineoplastic effects and, in combination with iodine supplement, attenuated the aggressiveness of these cells by decreasing expression of the markers of stem cells (CD44 and Sox2) and invasion (HIF and VEGF). These results allow us to propose the combination of shock waves and iodine as a possible adjuvant in breast cancer therapy.
The present work analyzes the antineoplastic effects of molecular iodine alone and in combination... more The present work analyzes the antineoplastic effects of molecular iodine alone and in combination with the neoadjuvant therapy FEC/TE (5-fluorouracil/epirubicin/cyclophosphamide or taxotere/epirubicin) in women with breast cancer. In this protocol the immunohistochemistry methodology for the quantification of the estrogen receptor and the proteins associated with the installation of the mesenchymal epithelium transition (e-cadherin and vimentin), immune response (CD8) and cell death (TUNEL) is described, and the methodology for transcriptomic analyses includes: RNA-Seq and transcriptomic analysis; pathway enrichment analysis; validation of the immune response and epithelium/stroma rate and, prediction of the transcription factor regulatory network and peroxisome proliferator-activated receptors type gamma (PPARg) interaction
This study analyzes oral supplement of molecular iodine (I2) alone and in combination with the ne... more This study analyzes oral supplement of molecular iodine (I2) alone and in combination with the neoadjuvant therapy 5-fluorouracil/epirubicin/cyclophosphamide or taxotere/epirubicin (FEC/TE) in women with Early (stage II) and Advanced (stage III) breast cancer. In the Early group, 30 women were treated with I2 (5 mg/day) or placebo (colored water) for 7–35 days before surgery. For the Advanced group, 30 patients received I2 or placebo along with FEC/TE treatment. After surgery, all patients received FEC/TE + I2 for 170 days. I2 supplementation showed a significant attenuation of the side effects and absence of tumor chemoresistance. Control, I2, FEC/TE, and FEC/TE+I2 groups exhibit response rate of 0, 33%, 73%, and 100%, respectively, and a pathologic complete response of 18%, and 36% in the last two groups. Five-year disease-free survival rate was significantly higher in patients with I2 supplement before and after surgery compared to those receiving the supplement only after surger...
Background: Cancer stem cells (CSC) are characterized by deregulated self-renewal, tumorigenicity... more Background: Cancer stem cells (CSC) are characterized by deregulated self-renewal, tumorigenicity, metastatic potential, aberrant stemness signaling pathways, resistance to conventional therapy, and the ability to give rise to a progeny of proliferating cells that constitute the bulk of tumors. Targeting CSC will provide novel treatments for cancer. Different investigations have focused on developing complementary approaches that involve natural compounds that decrease chemo-resistance and reduce the side effects of conventional therapies. Since, it has been reported that molecular iodine (I 2) exhibits antineoplastic effects and decreases tumor progression in some cancer models, we evaluated the potential effect of I 2 on cell cultures enriched in cervical cancer stem-like cells. Methods: HeLa and SiHa cervical cancer cells were treated with 200uM I 2 for 24 h. After time, cells were cultured in CSC-conditioned medium (cervospheres) and viability assays were performed. Following, tumorigenic capabilities in cervospheres treated with I 2 were evaluated in NOD/SCID mice. HeLa monolayer cells untreated and their respective cervosphere cells treated or untreated with 200 μM of I 2 for 24 h were xenotransplanted subcutaneously at different amounts and mice were monitored for at least 2 months. Results: In the present study, monolayer and CSC-enriched cultures (cervospheres) from cervical cancer-derived cell lines, HeLa and SiHa, showed that 200uM I 2 supplementation inhibits proliferation of both and decreased their tumorigenic capacity, in vivo. This antineoplastic effect of I 2 was accompanied by diminished expression of stemness markers including CD49f, CK17, OCT-4, NANOG, SOX2, and KLF4, as well as increased expression and activation of PPARγ receptors. Conclusions: All this data led us to suggest a clinical potential use of I 2 for targeting CSC and improve current treatments against cervical cancer.
Oxidative stress and inflammation are involved in the development and/or progression of benign pr... more Oxidative stress and inflammation are involved in the development and/or progression of benign prostatic hyperplasia (BPH). Molecular iodine (I2) induces antiproliferative and apoptotic effects in prostate cancer cells, but it is unknown if I2 regulates oxidative stress in the normal and/or tumoral prostate. The purpose of this study was to analyze the effects of I2 and celecoxib (Cxb) on oxidative stress and inflammation in a model of prostatic hyperplasia. Cxb was used as positive control of cyclooxygenase-2 (COX-2) inhibition. Prostatic hyperplasia was induced in male Wistar rats (170g) with testosterone (5mg/kg/week, for three weeks). One week before hyperplasia induction, I2 (25mg/day/rat) or Cxb (1.25mg/day/rat) was supplied for four weeks in the drinking water. Prostatic hyperplasia was evaluated by histological analysis, DNA content, and/or proliferating cell nuclear antigen (PCNA) expression. Lipoperoxidation (malondialdehyde) and nitrite (NO2-) levels were analyzed by colo...
The original version of this article unfortunately contained a mistake. The lable in Fig. 4a, b w... more The original version of this article unfortunately contained a mistake. The lable in Fig. 4a, b was incorrect in the published version of the article. The scale bar has the label ''50 microseconds'' instead of ''50 micrometers''. The corrected Fig. 4 is given below.
Shock waves are known to permeabilize eukaryotic cell membranes, which may be a powerful tool for... more Shock waves are known to permeabilize eukaryotic cell membranes, which may be a powerful tool for a variety of drug delivery applications. However, the mechanisms involved in shock wave-mediated membrane permeabilization are still poorly understood. In this study, the effects on both the permeability and the ultrastructural features of two human cell lineages were investigated after the application of underwater shock waves in vitro. Scanning Electron Microscopy of cells derived from a human embryo kidney (HEK)-293 and Michigan Cancer Foundation (MCF)-7 cells, an immortalized culture derived from human breast adenocarcinoma, showed a small amount of microvilli (as compared to control cells), the presence of hole-like structures, and a decrease in cell size after shock wave exposure. Interestingly, these effects were accompanied by the permeabilization of acid and macromolecular dyes and gene transfection. Trypan blue exclusion assays indicated that cell membranes were porated during...
Archivos Latinoamericanos De Nutricion, Sep 1, 2005
Breast cancer is the most common worldwide neoplasia in women. The totality of etiology factors o... more Breast cancer is the most common worldwide neoplasia in women. The totality of etiology factors of breast cancer is unknown and thus an effective preventive strategy has not been developed. Risk factors associated to breast cancer can be grouped into three broad categories: a) family history (hereditary) factors, b) endocrine and reproductive factors and c) environmental and life-style factors including diet. Animal models of chemical induced mammary carcinogenesis with 7, 12-dimethylbenz[a]anthracene and N-methyl-N-nitrosourea have been useful in the study of biology, treatment and prevention of breast cancer. In this review we show the usefulness and advantages of animal models in the study of nutritional factors associated with breast cancer in order to propose new prevention strategies. We review briefly different experimental approaches as well as some physiologic effects and mechanisms of some nutritional factors studied with animal models of mammary carcinogenesis. Nutritional factors reviewed were: a) energy restriction and high-fat intake, b) soy and phytoestrogens, c) retinoids and carotenoids, d) conjugated linoleic acid, and e) brown seaweed and iodine.
Molecular medicine (Cambridge, Mass.), Jan 26, 2016
Prostate cancer cells are responsive to adrenergic and thyroid stimuli. It is well established th... more Prostate cancer cells are responsive to adrenergic and thyroid stimuli. It is well established that β-adrenergic activation (PKA/CREB) promotes cancer progression, but the role of thyroid hormones (TH) is poorly understood. We analyzed the effects of β-adrenergic stimulation (isoproterenol, ISO), and/or TH on neuroendocrine (NE) differentiation and cell invasion, using in vivo (LNCaP tumor) and in vitro models (LNCaP and DU145 human cells). Nude mice were inoculated with LNCaP cells and were treated for 6 weeks with ISO (200 μg/day), triiodothyronine (T3, 2.5 μg/day), or both. ISO alone reduced tumor growth but increased tumor expression of cAMP response element (CRE)-dependent genes (real-time PCR, chromogranin A, neuron specific enolase, survivin, VEGF, uPA, and MMP-9) and some proteins related to NE differentiation and/or invasiveness (synaptophysin, VEGF, pCREB). T3 reduced tumor growth and prevented the overexpression of ISO-stimulated factors, through a pCREB-independent mecha...
Most investigations of iodine metabolism in humans and animals have focused on its role in thyroi... more Most investigations of iodine metabolism in humans and animals have focused on its role in thyroid function. Public health policies have been established to supply deficient populations with the necessary amount of this element in order to eradicate the iodine deficiency diseases, primarily cretinism. However, considerable evidence indicates that iodine could also be implicated in the physiology of other organs. In humans, the total amount of iodine in the body is 30-50 mg, and less than 30% of it is present in the thyroid gland and its hormones. About 60% of total iodine is non-hormonal and is concentrated in extrathyroidal tissues, where its biological role is still unknown. Moreover, it has been demonstrated that iodine distribution in the organism depends on the chemical form of iodine ingested, and that molecular iodine (I 2) is not totally reduced to iodide (I-) in the blood before it is absorbed systemically from the gastrointestinal tract. Indeed, in iodine deficiency conditions, Iappears to be more efficient than I 2 in restoring the thyroid gland from a goitrous to a normal state, whereas I 2 supplementation diminishes the symptoms of mammary fibrosis in women, causes a 50-70% reduction in the occurrence of mammary cancer induced chemically in rats and exhibit antiproliferative and apoptotic effects in several human tumoral cell lines. Nevertheless, these findings have been viewed with caution, because exposure to moderate or high iodine is thought to be a potential risk to thyroid physiology. Careful examination shows that pathological responses occurred at low or moderate iodine intake in patients with underlying or evident thyroid pathology (e.g. Hashimoto's thyroiditis, history of treated Graves' diseases, etc.); in normal subjects, however, these pathologies occurred only with excessively high doses of iodine or iodide (>20 mg/day). No damaging effects were reported in either the human or animal studies that used therapeutic I 2 concentrations (3 to 15 mg/day). This issue will provide an overview of so-called extrathyroidal iodine, its role, and its potential clinical applications.
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