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Association among Vitamin D, Retinoic Acid-Related Orphan Receptors, and Vitamin D Hydroxyderivatives in Ovarian Cancer
- Source :
- Nutrients, Nutrients, Vol 12, Iss 3541, p 3541 (2020), Volume 12, Issue 11
- Publication Year :
- 2020
-
Abstract
- Vitamin D and its derivatives, acting via the vitamin D receptor (VDR) and retinoic acid-related orphan receptors &gamma<br />and &alpha<br />(ROR&gamma<br />and ROR&alpha<br />), show anticancer properties. Since pathological conditions are characterized by disturbances in the expression of these receptors, in this study, we investigated their expression in ovarian cancers (OCs), as well as explored the phenotypic effects of vitamin D hydroxyderivatives and ROR&gamma<br />/&alpha<br />agonists on OC cells. The VDR and ROR&gamma<br />showed both a nuclear and a cytoplasmic location, and their expression levels were found to be reduced in the primary and metastatic OCs in comparison to normal ovarian epithelium, as well as correlated to the tumor grade. This reduction in VDR and ROR&gamma<br />expression correlated with a shorter overall disease-free survival. VDR, ROR&gamma<br />were also detected in SKOV-3 and OVCAR-3 cell lines with increased expression in the latter line. 20-Hydroxy-lumisterol3 (20(OH)L3) and synthetic ROR&alpha<br />/ROR&gamma<br />agonist SR1078 inhibited proliferation only in the OVCAR-3 line, while 20-hydroxyvitamin-D3 (20(OH)D3) only inhibited SKOV-3 cell proliferation. 1,25(OH)2D3, 20(OH)L3, and SR1078, but not 20(OH)D3, inhibited spheroid formation in SKOV-3 cells. In summary, decreases in VDR, ROR&gamma<br />expression correlated with an unfavorable outcome for OC, and compounds targeting these receptors had a context-dependent anti-tumor activity in vitro. We conclude that VDR and ROR&gamma<br />expression can be used in the diagnosis and prognosis of OC and suggest their ligands as potential candidates for OC therapy.
- Subjects :
- 0301 basic medicine
Agonist
Adult
medicine.medical_specialty
medicine.drug_class
Receptors, Retinoic Acid
Retinoic acid
nuclear receptors
lcsh:TX341-641
vitamin D
Calcitriol receptor
Article
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Internal medicine
medicine
Vitamin D and neurology
Humans
Receptor
RORα
Aged
VDR
RORγ
Ovarian Neoplasms
ovarian cancers
Nutrition and Dietetics
Chemistry
Cell growth
Retinoic Acid Receptor alpha
Vitamins
Middle Aged
030104 developmental biology
Endocrinology
Nuclear receptor
Cell culture
030220 oncology & carcinogenesis
lipids (amino acids, peptides, and proteins)
Female
lcsh:Nutrition. Foods and food supply
Food Science
Subjects
Details
- ISSN :
- 20726643
- Volume :
- 12
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Nutrients
- Accession number :
- edsair.doi.dedup.....e97105d94befd87b82ccd16eb14765dd