Protective effects of vitamin D3 on fimbrial cells exposed to catalytic iron damage.
BACKGROUND
Recently, 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.


METHODS
The 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.


RESULTS
The 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.


CONCLUSIONS
This 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.
Physiology Laboratory, Department of Translational Medicine, UPO - University of Eastern Piedmont, Via Solaroli 17, Novara, 28100, Italy. francesca.uberti@med.uniupo.it.
Francesca
F
Uberti
Physiology Laboratory, Department of Translational Medicine, UPO - University of Eastern Piedmont, Via Solaroli 17, Novara, 28100, Italy.
Vera
V
Morsanuto
Department of Obstetrics and Gynecology, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan, 20122, Italy.
Debora
D
Lattuada
Department of Obstetrics and Gynecology, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan, 20122, Italy.
Barbara
B
Colciaghi
Department of Biomedical, Surgical and Dental Sciences, Milan State University, via Beldiletto 1, Milan, 20142, Italy.
Andrea
A
Cochis
Department of Obstetrics and Gynecology, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan, 20122, Italy.
Alessandro
A
Bulfoni
Department of Obstetrics and Gynecology, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan, 20122, Italy.
Paola
P
Colombo
Department of Obstetrics and Gynecology, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan, 20122, Italy.
Giorgio
G
Bolis
Physiology Laboratory, Department of Translational Medicine, UPO - University of Eastern Piedmont, Via Solaroli 17, Novara, 28100, Italy.
Claudio
C
Molinari
D015415:Biomarkers; D002384:Catalysis; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D005187:Fallopian Tubes / Q000166:cytology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007501:Iron / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D000072636:PAX8 Transcription Factor / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
D015415:Biomarkers; D000072636:PAX8 Transcription Factor; D020011:Protective Agents; D016271:Proto-Oncogene Proteins c-myc; D017382:Reactive Oxygen Species; D018167:Receptors, Calcitriol; D016159:Tumor Suppressor Protein p53; D002762:Cholecalciferol; D007501:Iron; D018631:ras Proteins
Catalytic iron; Epithelial ovarian cancer; Fimbrial secretory epithelial cells; Vitamin D3