Vitamin D receptor as a target for breast cancer therapy (abstract only)

Created February 2017

Endocr Relat Cancer. 2017 Feb 17. pii: ERC-16-0463. doi: 10.1530/ERC-16-0463. [Epub ahead of print]

Murray A1, Madden S2, Synnott NC3, Klinger R4, O'Connor D5, O'Donovan N6, Gallagher W7, Crown J8, Duffy M9.

* There have been strong hints that high vitamin D dosing along with adjusting cofactors may allow treating of many Cancers. * Note1: Breast Cancer is 4.6 times more likely to occur if have poor Vitamin D Receptor (see below) * Note2: Reducing Calcium intake and drinking lots of water both reduce "calcemic potential," Items in both VitaminDWiki categories Breast Cancer and Vitamin D Receptor are listed here: {category} 1. Vitamin D Receptor category has the following {include}

Considerable epidemiological evidence suggests that high levels of circulating vitamin D (VD) are associated with a decreased incidence and increased survival from cancer, i.e., VD may possess anti-cancer properties. The aim of this investigation was therefore to investigate the anti-cancer potential of a low calcemic vitamin D analogue, i.e., inecalcitol and compare it with the active form of vitamin D, i.e., calcitriol, in a panel of breast cancer cell lines (n = 15). Using the MTT assay, IC50 concentrations for response to calcitriol varied from 0.12 µM to >20 µM, while those for inecalcitol were significantly lower, ranging from 2.5 nM to 63 nM (p = 0.001). Sensitivity to calcitriol and inecalcitol was higher in VD receptor (VDR)-positive compared to VDR-negative cell lines (p = 0.0007 and 0.0080, respectively) and in ER-positive compared to ER-negative cell lines (p = 0.043 and 0.005, respectively). Using RNA-seq analysis, substantial but not complete overlap was found between genes differentially regulated by calcitriol and inecalcitol. In particular, significantly enriched gene ontology terms such as cell surface signalling and cell communication were found following treatment with inecalcitol but not with calcitriol. In contrast, ossification and bone morphogenesis were found significantly enriched following treatment with calcitriol but not with inecalcitol. Our preclinical results suggest that calcitriol and inecalcitol can inhibit breast cancer cell line growth, especially in cells expressing ER and VDR. As inecalcitol, is significantly more potent than calcitriol and has low calcemic potential, it should be further investigated for the treatment of breast cancer.

PMID: 28213567 DOI: 10.1530/ERC-16-0463

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Tags: Breast Cancer Vit D Receptor