Association between vitamin D and ovarian cancer development in <i>BRCA1</i> mutation carriers

Pejović, Tanja; Joshi, Sonali; Campbell, Shawn; Thisted, Sarah; Xu, Fan; Xu, Jing

doi:10.18632/oncotarget.27803

Cited by 6 publications

(3 citation statements)

References 47 publications

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“…In our cancer samples and consistent with the observations by Thill et al [ 72 ] and Cordes et al [ 73 ], VDR expression was heterogeneous, but the semiquantitative analysis indicated lower VDR levels in cancers than in normal ovaries ( Figure 4 ). While the paper was under review Pejovic et al [ 74 ] published similar association on vitamin D signaling and ovarian cancer. Reduced VDR expression in malignant tissues was also found in other tumors, such as cutaneous and uveal melanomas [ 54 , 55 , 75 ], urothelial bladder [ 56 ], colon [ 76 ], and lung [ 77 ] cancers.…”

Section: Discussionmentioning

confidence: 96%

Association among Vitamin D, Retinoic Acid-Related Orphan Receptors, and Vitamin D Hydroxyderivatives in Ovarian Cancer

et al. 2020

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Vitamin D and its derivatives, acting via the vitamin D receptor (VDR) and retinoic acid-related orphan receptors γ and α (RORγ and RORα), 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 RORγ/α agonists on OC cells. The VDR and RORγ 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 RORγ expression correlated with a shorter overall disease-free survival. VDR, RORγ, and RORα 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 RORα/RORγ 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, RORγ, and RORα 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 RORγ expression can be used in the diagnosis and prognosis of OC and suggest their ligands as potential candidates for OC therapy.

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Section: Discussionmentioning

confidence: 96%

Association among Vitamin D, Retinoic Acid-Related Orphan Receptors, and Vitamin D Hydroxyderivatives in Ovarian Cancer

et al. 2020

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“…The results showed that VDR protein levels in BRCA1mut ovarian surface epithelial cell cultures treated with calcitriol were increased by about 95 % compared with untreated cells. Furthermore, the same cancer cells treated with calcitriol showed a lower proliferation rate in a dose-dependent manner (132) .…”

Section: Cancermentioning

confidence: 94%

Sex differences in vitamin D metabolism, serum levels and action

Wierzbicka

Oczkowicz

2022

Br J Nutr

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The ubiquity of vitamin D metabolizing enzymes and vitamin D receptors in mammalian organisms suggests that vitamin D has pleiotropic effects. There are quite a few studies indicating the anticancer, cardioprotective and anti-diabetic effects of vitamin D, however, the best-documented actions of vitamin D are the regulation of calcium-phosphate balance and its effect on immune function. Vitamin D levels in organisms are modulated by many environmental and nonenvironmental factors. One potential factor that may influence vitamin D levels and effects is the sex of the individuals studied. This review focuses on the scientific evidence indicating different synthesis and metabolism of vitamin D in females and males, mainly from PubMed database sources. The article verifies the sex differences in vitamin D levels reported around the world. Moreover, the different effects of vitamin D on the musculoskeletal, cardiovascular, nervous, and immune systems, as well as cancer in males and females, were discussed. Most studies addressing sex differences in vitamin D levels and effects are observational studies with conflicting results. Therefore, carefully designed clinical trials and experiments on animal models should be carried out to determine the role of nonenvironmental factors that may differentiate vitamin D levels in females and males.

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“…With VD3 supplementation, VDR mRNA expression in cultured follicles was restored to levels observed in follicles developed in vivo (Xu et al 2018). VD3-enhanced VDR protein expression was also reported recently in cultured human ovarian surface epithelial cells (Pejovic et al 2020). Although data in follicular cells are absent, research in mouse preosteoblastic cells and human lymphoblastoid cell lines indicated that the number of VDRE occupied by the VD3-VDR-RXR complex were dynamically controlled by the VD ligand availability (Meyer et al 2010, Ramagopalan et al 2010.…”

Section: Vd Signaling In the Ovarian Folliclesmentioning

confidence: 71%

Vitamin D in follicular development and oocyte maturation

Wolf

Green

et al. 2021

Reproduction

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Vitamin D (VD) is a secosteroid hormone synthesized predominantly in the skin upon ultraviolet light exposure, which can also be obtained from dietary sources. In target cells, the bioactive VD binds to specific VD receptor to regulate downstream transcription of genes that are involved in a wide range of cellular processes. There is increasing recognition that the proper physiological levels of VD are critical for optimizing reproductive potential in women. The direct VD action in the ovary was first suggested in the 1980s. Since then, research has attempted to determine the role of VD in follicular development and oocyte maturation in animal models and clinical settings. However, data published to date are inconclusive due to the complexity in VD metabolism and the fact that VD actions are pervasive in regulating physiological functions in various systems, including the reproductive, endocrine and nervous systems that control reproduction. This review summaries in vitro, in vivo, and clinical evidence regarding VD metabolism and signaling in the ovary, as well as VD-regulated or VD-associated ovarian follicular development, steroidogenic function, and oocyte maturation. It is suggested that adequate animal models are needed for well-controlled studies to unravel molecular mechanisms of VD action in the ovary. For clinical studies, follicular development and function may be evaluated more effectively in a relatively homogeneous patient population under a well-controlled experimental design. A comprehensive understanding of VD-regulated folliculogenesis and oogenesis will provide critical insight into the impact of VD in female reproductive health.

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Association between vitamin D and ovarian cancer development in BRCA1 mutation carriers

Cited by 6 publications

References 47 publications

Association among Vitamin D, Retinoic Acid-Related Orphan Receptors, and Vitamin D Hydroxyderivatives in Ovarian Cancer

Association among Vitamin D, Retinoic Acid-Related Orphan Receptors, and Vitamin D Hydroxyderivatives in Ovarian Cancer

Sex differences in vitamin D metabolism, serum levels and action

Vitamin D in follicular development and oocyte maturation

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