Abstract
Several studies show that triple-negative breast cancer (TNBC) patients have the lowest vitamin D concentration among all breast cancer types, suggesting that this vitamin may induce a protective effect against TNBC. This effect of the active metabolite of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D), can be attributed to its potential to modulate proliferation, differentiation, apoptosis, inflammation, angiogenesis, invasion and metastasis and is supported by many in vitro and animal studies, but its exact mechanism is poorly known. In a fraction of TNBCs that harbor mutations that cause the loss of function of the DNA repair-associated breast cancer type 1 susceptibility (BRCA1) gene, 1,25(OH)2D may induce protective effects by activating its receptor and inactivating cathepsin L-mediated degradation of tumor protein P53 binding protein 1 (TP53BP1), preventing deficiency in DNA double-strand break repair and contributing to genome stability. Similar effects can be induced by the interaction of 1,25(OH)2D with proteins of the growth arrest and DNA damage-inducible 45 (GADD45) family. Further studies on TNBC cell lines with exact molecular characteristics and clinical trials with well-defined cases are needed to determine the mechanism of action of vitamin D in TNBC to assess its preventive and therapeutic potential.
Highlights
Studies on the anticancer properties of vitamin D bring conflicting results and the reason for this conflict has not yet been identified
These results suggest that some vitamin D compounds may have the potential to prevent triple-negative breast cancer through the regulation of breast cancer stem cells (BCSCs)
The growth arrest and DNA damage-inducible 45 alpha (GADD45A) gene is important in the cellular reaction to stress as it is upregulated in stress conditions induced by various factors, including DNA-damaging agents [147]
Summary
Studies on the anticancer properties of vitamin D bring conflicting results and the reason for this conflict has not yet been identified (reviewed in [1,2]). The essential role of VDR in mediating vitamin D anticancer effects in TNBC was shown by LaPorta and Welsh, who demonstrated that 1,25(OH)2D downregulated genes related to breast cancer invasion and metastasis in cells from a mouse model of TNBC [29]. These effects were not observed in mice with VDR knockout, but the reintroduction of human VDR restored the ability of 1,25(OH)2D to inhibit the proliferation of TNBC-like cells. VDR is necessary to mediate effects of vitamin D in TNBC cells
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