Antiproliferative effects of 1,25-dihydroxyvitamin D3 on breast cells: a mini review

Abstract

The hormone 1,25-dihydroxyvitamin D 3 (1,25-(OH) 2 D 3 ), the active form of vitamin D 3 , is an important regulator of calcium homeostasis, exerts antiproliferative effects on various cell systems and can induce differentiation in some kinds of hematopoietic cells. These effects are triggered by its receptor, vitamin D receptor (VDR), a phosphoprotein member of the nuclear receptor superfamily, which functions as a transcriptional factor. VDR binds as a heterodimer with retinoid X receptor (R X R) to hexameric repeats, characterized as vitamin Dresponsive elements present in the regulatory region of target genes such as osteocalcin, osteopontin, calbindin-D 28K , calbindin-D 9K , p21 WAF1/CIP1 , TGF-ß2 and vitamin D 24-hydroxylase. Many factors such as glucocorticoids, estrogens, retinoids, proliferation rate and cell transformation can modulate VDR levels. VDR is expressed in mammary tissue and breast cancer cells, which are potential targets to hormone action. Besides having antiproliferative properties, vitamin D might also reduce the invasiveness of cancer cells and act as an antiangiogenesis agent. All of these antitumoral features suggest that the properties of vitamin D could be explored for chemopreventive and therapeutic purposes in cancer. However, hypercalcemia is an undesirable side effect associated with pharmacological doses of 1,25-(OH) 2 D 3 . Some promising 1,25-(OH) 2 D 3 analogs have been developed, which are less hypercalcemic in spite of being potent antiproliferative agents. They represent a new field of investigation. Key words Mechanism of action of vitamin DVitamin D is in fact a secosteroid hormone which in its active form, 1,25-dihydroxyvitamin D 3 (1,25-(OH) 2 D 3 ), is an important regulator of bone development and metabolism and calcium homeostasis. Besides these well-known functions on classical target tissues (bone, kidneys, intestine, parathyroids), 1,25-(OH) 2 D 3 plays an important role in the regulation of cell growth and differentiation in cells other than its classical targets.Vitamin D can be obtained in two distinct ways, i.e., through dietary intake (fatty fish, fish oil, mushrooms, vitamin D-fortified food such as milk) and/or the endogenous pathway, in which the precursor 7-dehydrocholesterol, present in the skin, upon the action of sunlight becomes pre-vitamin D, the latter

Impact of vitamin D supplementation on endothelial and inflammatory markers in adults: A systematic review

“…As the number of VDR decreases following a reduction in oestrogen, this leads to alterations in the quantity and functionality of the VDR in target tissues [54]. Target cell response to vitamin D is dependent on VDR levels and factors such as glucocorticoids and retinoids as well as oestrogen, are known to modulate VDR levels [55]. This is supported by evidence from studies in animal models (rats), that shows oestrogen increases the expression of VDR in various tissues such as endothelial, colon, immune and smooth muscle cells [56,57].…”

Vitamin D and Reduced Risk of Breast Cancer: A Population-Based Case-Control Study

“…[12][13][14]. In carcinogen-exposed rats, 1,25(OH) 2 D or its analogues have been shown to reduce the incidence and size and delay the development of mammary tumors (12)(13)(14).…”

Association of Vitamin D–Related Information from a Telephone Interview with 25-Hydroxyvitamin D

“…1-3). It also plays an important role in the regulation of cell growth and differentiation (4). Vitamin D is produced on exposure to UV light, which converts 7-dihydrocholesterol to vitamin D (1).…”