The Journal of Steroid Biochemistry and Molecular Biology
Vitamin D and breast cancer: Inhibition of estrogen synthesis and signaling☆,☆☆
Introduction
Breast cancer (BCa) is the most common cancer in women in the United States with over 180,000 new cases in 2008 [1]. Estrogens drive the proliferation of mammary epithelial cells and therefore promote the growth of estrogen receptor positive (ER+) BCa. Approximately 70% of BCa is ER+ and is therefore amenable to hormonal treatments that ablate estrogen production or block estrogen action [2]. In spite of the available treatments, the incidence of BCa continues to rise and increasing emphasis is being placed on BCa chemoprevention, including approaches to reduce exposure to carcinogens and the use of nutritional agents to prevent and/or delay the development of BCa.
Calcitriol, the hormonally active form of vitamin D (1,25-dihydroxyvitamin D3), plays an important role in calcium homeostasis through its actions in intestine, kidney and bone [3]. In the recent years it has been recognized that in addition to its actions on calcium and bone homeostasis, calcitriol also exhibits anti-proliferative and pro-differentiation activities indicating its potential use in the prevention and treatment of several cancers including BCa [4], [5], [6], [7], [8], [9], [10], [11].
Section snippets
Epidemiology
Epidemiological studies report lower incidence and mortality rates from BCa in regions with greater solar UV-B exposure [12]. The potential benefit from sunlight is attributed to vitamin D, since UV light is essential for the cutaneous synthesis of vitamin D [3]. Women who develop BCa are predominantly postmenopausal and estrogen deficiency and aging are associated with vitamin D deficiency [13]. There appears to be an inverse association between BCa risk and the levels of serum
Growth arrest and differentiation
Several studies have shown that calcitriol inhibits the growth of human BCa cell lines (reviewed in [5], [6], [26]). In general ER+ BCa cell lines appear to be more sensitive to the growth inhibitory effects of calcitriol than ER-negative cell lines [16]. In ER+ cells such as MCF-7, calcitriol induces cell cycle arrest in the G0/G1 phase of the cell cycle by increasing the expression of cyclin-dependent kinase inhibitors such as p21Waf/Cip1, decreasing cyclin-dependent kinase activity and
Anti-inflammatory effects
A variety of stimuli trigger chronic inflammation, which has been recognized as a risk factor for cancer development [40], [41]. Cancer-related inflammation is characterized by the presence of inflammatory cells at the tumor sites and the over-expression of inflammatory mediators such as cytokines, chemokines, prostaglandins (PGs) and reactive oxygen and nitrogen species in tumor tissue [40], [41], [42], [43]. Many of these pro-inflammatory mediators activate angiogenic switches usually under
Summary and conclusions
Calcitriol exhibits anti-proliferative effects in BCa cells through a variety of mechanisms and retards tumor growth in animal models of BCa. Our recent research has identified several new calcitriol target genes revealing additional molecular pathways of calcitriol action. Calcitriol suppresses the expression of COX-2 and stimulates 15-PGDH expression thereby reducing the levels of biologically active PGs in BCa cells. We propose that calcitriol inhibition of the PG pathway contributes
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Overview of vitamin D actions in cancer
2023, Feldman and Pike's Vitamin D: Volume Two: Disease and TherapeuticsEncapsulation for breast cancer treatment
2023, Principles of Biomaterials Encapsulation: Volume 2An update on vitamin D signaling and cancer
2022, Seminars in Cancer BiologyCitation Excerpt :Other studies, however, proposed tumor non-autonomous effects of vitamin D on breast cancer. For example, 1,25(OH)2D3 reduces the adverse effects of obesity on breast cancer by acting on pathways both within breast cancer cells and surrounding adipocytes by suppressing estrogen synthesis and signaling via the control of prostaglandin E2 synthesis by PTGS2 (prostaglandin-endoperoxide synthase 2) and degradation, and the inhibition of ER and PTGER2 (prostaglandin E receptor 2) and CYP19A1 (aromatase) [177,178]. Giving the important role of estradiol promoting the proliferation of breast cancer cells at least at early stages of tumor development, these effects on estrogen signaling may protect against breast cancer at the initial steps.
Clinical significance of serum 25 hydroxyvitamin D in breast cancer: An Indian scenario
2020, Journal of Steroid Biochemistry and Molecular Biology
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This work was supported by NCI grant CA130991 and Komen Foundation grant 070101 to D.F.
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Special issue selected article from the 14th Vitamin D Workshop held at Brugge, Belgium on October 4–8, 2009.