Type

Journal Article

Authors

Michael J Duffy
John Crown
William Gallagher
Norma O'Donovan
Darran O'Connor
Rut Klinger
Naoise C Synnott
Stephen F Madden
Alyson Murray

Subjects

Medicine & Nursing

Topics
anti cancer properties vitamin d cancer cell lines cell growth cancer therapy breast cancer cell communication rna seq

Vitamin D receptor as a target for breast cancer therapy. (2017)

Abstract 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 calcaemic 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, whereas 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 after treatment with inecalcitol but not with calcitriol. In contrast, ossification and bone morphogenesis were found significantly enriched after 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 calcaemic potential, it should be further investigated for the treatment of breast cancer.
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Full list of authors on original publication

Michael J Duffy, John Crown, William Gallagher, Norma O'Donovan, Darran O'Connor, Rut Klinger, Naoise C Synnott, Stephen F Madden, Alyson Murray

Experts in our system

1
Michael J Duffy
University College Dublin
 
2
John Crown
Dublin City University
Total Publications: 104
 
3
William M Gallagher
University College Dublin
Total Publications: 148
 
4
Norma O'Donovan
Dublin City University
Total Publications: 59
 
5
Darran P O'Connor
Royal College of Surgeons in Ireland
Total Publications: 43
 
6
Naoise C Synnott
Dublin City University
 
7
Stephen F Madden
Dublin City University
Total Publications: 45
 
8
Alyson Murray
Dublin City University
Total Publications: 6