Protection against cellular stress by 25‐hydroxyvitamin D₃ in breast epithelial cells

Abstract

25-Hydroxyvitamin D(3) (25(OH)D(3)) is a prohormone and a major vitamin D metabolite. The discovery of (25(OH)D(3)) 1 alpha-hydroxylase in many vitamin D target organs has yielded an increased interest in defining the role(s) of 25(OH)D(3) in these tissues. The etiology of cancer appears to be complex and multi-factorial. Cellular stress (e.g., DNA damage, hypoxia, oncogene activation) has been identified as one of the key factors responsible for initiating the carcinogenesis process. In this study, we investigated whether 25(OH)D(3) protects breast epithelial cells from cellular stress using an established breast epithelial cell line MCF12F. To better elucidate the role of 25(OH)D(3) in the stress response, we used multiple in vitro stress models including serum starvation, hypoxia, oxidative stress, and apoptosis induction. Under all these stress conditions, 25(OH)D(3) (250 nmol/L) treatment significantly protected cells against cell death. Low-serum stress induced p53 expression accompanied with downregulation of PCNA, the presence of 25(OH)D(3) consistently inhibited the alteration of p53 and PCNA, suggesting that these molecules were involved in the stress process and may be potential target genes of 25(OH)D(3). miRNA microarray analysis demonstrated that stress induced by serum starvation caused significant alteration in the expression of multiple miRNAs including miR182, but the presence of 25(OH)D(3) effectively reversed this alteration. These data suggest that there is a significant protective role for 25(OH)D(3) against cellular stress in the breast epithelial cells and these effects may be mediated by altered miRNA expression.

20-Hydroxyvitamin D2 is a noncalcemic analog of vitamin D with potent antiproliferative and prodifferentiation activities in normal and malignant cells

“…S7B). The latter is consistent with recent reports indicating that 25(OH)D 3 can also act as an agonistic vitamin D receptor ligand (35) or through another mechanism (49).…”

Regulation of CYP24 splicing by 1,25-dihydroxyvitamin D3 in human colon cancer cells

“…The concentrations of other reagents were determined by preliminary experiments in our laboratory and from reports in the literature. Cell proliferation was determined by crystal violet assay as described previously (Peng et al 2010). Biopsy samples were collected from high-risk colon cancer patients during colonoscopy at University of Illinois hospital.…”

The Emerging Role of MicroRNAs in the Regulation of Gene Expression by Nutrients

“…Additionally, it was observed that the inhibition of miR-32 function by the administration of an RNA molecule that is complementary to miR-32 is able to increase the efficiency of cytotoxic therapy [40]. In a similar way, treatment with vitamin D was found to reverse the increase in cell death and in the expression of miR-182 in normal breast cells subjected to stress by growing in low-serum medium culture [41]. Another effect of vitamin D administration is the attenuation of proliferation of human prostate cancer cells when co-administered with testosterone; this treatment produced the upregulation of expression of miR-21, -22, -29a, -29b, -134, -371-5p, and -1207-5p and the downregulation of miR-17, -18, and -20a, that are part of the miR-17/92 cluster [42].…”