Vitamin D Signaling in Inflammation and Cancer: Molecular Mechanisms and Therapeutic Implications

Abstract

Vitamin D and its active metabolites are important nutrients for human skeletal health. UV irradiation of skin converts 7-dehydrocholesterol into vitamin D3, which metabolized in the liver and kidneys into its active form, 1α,25-dihydroxyvitamin D3. Apart from its classical role in calcium and phosphate regulation, scientists have shown that the vitamin D receptor is expressed in almost all tissues of the body, hence it has numerous biological effects. These includes fetal and adult homeostatic functions in development and differentiation of metabolic, epidermal, endocrine, neurological and immunological systems of the body. Moreover, the expression of vitamin D receptor in the majority of immune cells and the ability of these cells to actively metabolize 25(OH)D3 into its active form 1,25(OH)2D3 reinforces the important role of vitamin D signaling in maintaining a healthy immune system. In addition, several studies have showed that vitamin D has important regulatory roles of mechanisms controlling proliferation, differentiation and growth. The administration of vitamin D analogues or the active metabolite of vitamin D activates apoptotic pathways, has antiproliferative effects and inhibits angiogenesis. This review aims to provide an up-to-date overview on the effects of vitamin D and its receptor (VDR) in regulating inflammation, different cell death modalities and cancer. It also aims to investigate the possible therapeutic benefits of vitamin D and its analogues as anticancer agents.

Breast Cancer—Epidemiology, Risk Factors, Classification, Prognostic Markers, and Current Treatment Strategies—An Updated Review

“…Attempts are continually made to analyze the effects of vitamin intake (vitamin C, vitamin E, B-group vitamins, folic acid, multivitamin) on the risk of breast cancer, nevertheless, the data remains inconsistent and not sufficient to compare the results and draw credible data [ 108 ]. In terms of breast cancer, most studies are currently focused on vitamin D supplementation confirming its potentially protective effects [ 109 , 110 , 111 ]. High serum 25-hydroxyvitamin D levels are associated with a lower incidence rate of breast cancer in premenopausal and postmenopausal women [ 110 , 112 ].…”

Macrofungi as a Nutraceutical Source: Promising Bioactive Compounds and Market Value

“…In recent years, several clinical trials have been performed to investigate the therapeutic value of vitamin D in hyperproliferative diseases, secondary hyperparathyroidism, multiple sclerosis, rheumatoid arthritis, Crohn disease, type I diabetes, systemic lupus erythematosus, and various malignancies [222,223]. Vitamin D also helps in maintaining a healthy immune system by signaling the immune cells and promoting their ability to metabolize 25(OH)D3 into its active form 1,25(OH)2D3 [224].…”

The Impact of the Circadian Clock on Skin Physiology and Cancer Development

“…Moreover, organ transplant recipients have a significantly elevated risk of developing skin cancer because of the post-operative immunosuppressive drugs that are needed [ 19 , 20 , 21 , 22 , 23 ]. In addition to contributing to immune function, Vitamin D, which is synthesized in the skin in a UVB-dependent manner, also influences skin carcinogenesis due to its effects on DNA repair, proliferation, differentiation, and neuroendocrine pathways [ 24 , 25 , 26 , 27 , 28 ]. Lastly, exposure to certain viruses (human papilloma virus, Merkel cell polyomavirus) and other environmental carcinogens is also thought to contribute to skin carcinogenesis in certain patients [ 29 , 30 , 31 , 32 ].…”