Fimbrial Cells Exposure to Catalytic Iron Mimics Carcinogenic Changes

Lattuada, D.; Uberti, Francesca; Colciaghi, Barbara; Morsanuto, Vera; Maldi, Elena; Squarzanti, Diletta Francesca; Molinari, Claudio; Boldorini, Renzo; Bulfoni, A; Colombo, Paola; Bolis, Giorgio

doi:10.1097/igc.0000000000000379

Cited by 24 publications

(28 citation statements)

References 40 publications

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“…The cells cultured in chamber slides were fixed using an iced fixative solution (3.7 % formaldehyde, 3 % sucrose in PBS 1X) for 20 min at RT, permeabilized with ice 0.5 % Triton X-100 in PBS 1X in ice at 4 °C for 20 min, incubated with 3 % hydrogen peroxide in PBS 1X for 8 min and then maintained in a blocking solution (PBS 1X with 3 % albumin from bovine serum-BSA, Sigma, Milan, Italy) for 1 h in at RT, as previously described [ 36 ]. After this time the slides were incubated overnight at 4 °C in a humidified chamber with specific primary antibody VDR receptor (1:50).…”

Section: Methodsmentioning

confidence: 99%

Role of vitamin D3 combined to alginates in preventing acid and oxidative injury in cultured gastric epithelial cells

et al. 2016

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BackgroundGastric diseases are a worldwide problem in modern society, as reported in the USA, in the range of 0.5–2 episodes/year/person and an incidence of 5–100 episodes/1000/week according to seasons and age. There is convincing evidence that oxidative stress is involved in the pathogenesis of acute gastric injury. Acid secreted from gastric parietal cells determines mucosal injuries which in turn cause inflammation and oxidative stress. Consequent inflammation produces free radicals by mitochondria thus causing lipid peroxidation, oxidative and acidic stress, which can lead to cell apoptosis. Vitamin D3, the active form of vitamin D, may counteract intracellular cell death and improve epithelial regeneration.MethodsThis study was planned to assess whether vitamin D3 is a protective factor against acid injury and oxidative stress in gastric epithelial cells. Primary epithelial cells and GTL-16 cells have been used to test the effects of Grisù® alone or in combination with vitamin D3 during oxidative stress or high acid exposition measuring cell viability, ROS production, cellular adhesion time along with apoptotic, autophagic and survival pathways. The combined effect of Grisù® and vitamin D3 was found more effective in counteracting the negative consequences of oxidative stress and acidity conditions than some other gastroprotective agents, such as Maalox® or Gaviscon®.ResultsIn case of oxidative stress or acidity condition the stimulation with Grisù® alone caused an improvement of cell viability and a reduction of ROS production on epithelial gastric cells. In addition, the adhesion time of the cells was improved. All these effects were increased by the presence of vitamin D3. Similar data were also observed in primary gastric epithelial cells confirming the results obtained in GTL-16 cells.ConclusionsThese results suggest that Grisù® in combination with vitamin D3 may exert a gastroprotective effect to maintain or restore the integrity of gastric epithelium through an antioxidant pathway, inhibiting apoptosis and activating survival kinases. Moreover, the combination of Grisù® and vitamin D3 improves cell viability and decreases ROS production compared to other gastroprotective agents combined with vitamin D3. All these data were validated using primary cells isolated from gastric tissue.Electronic supplementary materialThe online version of this article (doi:10.1186/s12876-016-0543-z) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Role of vitamin D3 combined to alginates in preventing acid and oxidative injury in cultured gastric epithelial cells

et al. 2016

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“…Iron deposits have also been identified in the fallopian tube (Seidman, 2013). Fimbrial secretory epithelial cells treated with increasing doses of iron elicited increased cellular proliferation along with changes in p53, MAPK, AKT, and c-Myc proteins, as well as increased ROS species (0.05–100mM) (Lattuada et al, 2015). Furthermore, vitamin D3 could oppose the oxidative stress-induced events mediated by iron in these fimbrial cells (Uberti et al, 2016).…”

Section: Initiation Of Ovarian Cancer By Persistent Oxidative Strementioning

confidence: 99%

Iron overload and altered iron metabolism in ovarian cancer

Rockfield

Raffel

Mehta

et al. 2017

Biological Chemistry

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Iron is an essential element required for many processes within the cell. Dysregulation in iron homeostasis due to iron overload is detrimental. This nutrient is postulated to contribute to the initiation of cancer; however, the mechanisms by which this occurs remain unclear. Defining how iron promotes the development of ovarian cancers from precursor lesions is essential for developing novel therapeutic strategies. In this review, we discuss (1) how iron overload conditions may initiate ovarian cancer development, (2) dysregulated iron metabolism in cancers, (3) the interplay between bacteria, iron, and cancer, and (4) chemotherapeutic strategies targeting iron metabolism in cancer patients.

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“…It has recently been demonstrated that Fe 3+ , derived from menstrual reflux, recently defined as “incessant menstruation” [ 25 ], is able to induce an increase in fimbrial cell viability and proliferative capacity and to activate principal oncogenes (p53, pan-Ras, Ki67 and c-Myc). So, it has been confirmed that Fe 3+ is capable to induce carcinogenic changes and represents the main non-genetic risk factor for ovarian cancer [ 26 ]. For this reason, Fe 3+ can be considered a putative candidate as a transforming agent from normal human fimbrial cells into cancer cells maintaining physiological conditions of the menstrual cycle through oxidative stress and consequent oncogenes activations.…”

Section: Introductionmentioning

confidence: 99%

“…This research was planned to study the role of VitD to prevent oxidative injury induced by Fe 3+ exposition in primary fimbrial cells culture, because recent studies have hypothesized that fimbrial fallopian tubes are the site where most serous ovarian cancers develop [ 27 , 28 ], and the cells are subjected, to a constant carcinogenic stimulus represented by Fe 3+ [ 26 ], especially in presence of low levels of serum VitD.…”

Section: Introductionmentioning

confidence: 99%

Protective effects of vitamin D3 on fimbrial cells exposed to catalytic iron damage

et al. 2016

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BackgroundRecently, vitamin D3 (1alpha, 25-dihydroxyvitamin D) has shown its capability to take part in many extraskeletal functions and its serum levels have been related to patient survival rate and malignancy of many types of neoplasms, including ovarian cancers. Catalytic iron is a free circulating form of iron that is able to generate reactive oxygen species and consequently to promote a number of cellular and tissutal dysfunctions including tumorigenesis. In fertile women an important source of catalytic iron is derived from retrograde menstruation. Epithelial secretory cells from fimbriae of fallopian tubes are greatly exposed to catalytic iron derived from menstrual reflux and so represent the site of origin for most serous ovarian cancers.The aim of this study was to assess whether vitamin D3 can play a role in counteracting catalytic iron-induced oxidative stress in cells from fimbriae of fallopian tubes.MethodsThe cells, isolated from women undergoing isteroannessiectomy, were treated with catalytic iron 50-75-100 mM and vitamin D3 at a concentration ranging from 0.01 to 10 nM to study cell viability, radical oxygen species production, p53, pan-Ras, Ki67 and c-Myc protein expressions through Western Blot, and immunocytochemistry or immunofluorescence analysis.ResultsThe pre-treatment with vitamin D3 1 nM showed its beneficial effects that consists in a significant decrease in ROS production. In addition a novel finding is represented by the demonstration that pre-treatment with vitamin D3 is also able to significantly counteract tumoral biomarkers activation, such as p53, pan-Ras, Ki67 and c-Myc, and consequently the catalytic iron-induced cellular injury.ConclusionsThis study demonstrates for the first time that vitamin D3 plays an important role in preventing catalytic iron-dependent oxidative stress in cultured fimbrial cells. These results support the hypothesis that vitamin D3 could counteract carcinogenic changes induced by catalytic iron.

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Fimbrial Cells Exposure to Catalytic Iron Mimics Carcinogenic Changes

Cited by 24 publications

References 40 publications

Role of vitamin D3 combined to alginates in preventing acid and oxidative injury in cultured gastric epithelial cells

Role of vitamin D3 combined to alginates in preventing acid and oxidative injury in cultured gastric epithelial cells

Iron overload and altered iron metabolism in ovarian cancer

Protective effects of vitamin D3 on fimbrial cells exposed to catalytic iron damage

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