Abstract
Increasing interest in studying the role of vitamin D in cancer has been provided by the scientific literature during the last years, although mixed results have been reported. Vitamin D deficiency has been largely associated with various types of solid and non-solid human cancers, and the almost ubiquitous expression of vitamin D receptor (VDR) has always led to suppose a crucial role of vitamin D in cancer. However, the association between vitamin D levels and the risk of solid cancers, such as colorectal, prostate and breast cancer, shows several conflicting results that raise questions about the use of vitamin D supplements in cancer patients. Moreover, studies on vitamin D supplementation do not always show improvements in tumor progression and mortality risk, particularly for prostate and breast cancer. Conversely, several molecular studies are in agreement about the role of vitamin D in inhibiting tumor cell proliferation, growth and invasiveness, cell cycle arrest and inflammatory signaling, through which vitamin D may also regulate cancer microenvironment through the activation of different molecular pathways. More recently, a role in the regulation of cancer stem cells proliferation and short non-coding microRNA (miRNAs) expression has emerged, conferring to vitamin D a more crucial role in cancer development and progression. Interestingly, it has been shown that vitamin D is able not only to potentiate the effects of traditional cancer therapy but can even contribute to overcome the molecular mechanisms of drug resistance—often triggering tumor-spreading. At this regard, vitamin D can act at various levels through the regulation of growth of cancer stem cells and the epithelial–mesenchymal transition (EMT), as well as through the modulation of miRNA gene expression. The current review reconsiders epidemiological and molecular literature concerning the role of vitamin D in cancer risk and tumor development and progression, as well as the action of vitamin D supplementation in potentiating the effects of drug therapy and overcoming the mechanisms of resistance often triggered during cancer therapies, by critically addressing strengths and weaknesses of available data from 2010 to 2020.
Highlights
The term vitamin D is referred to liposoluble steroid hormones wrongly qualified as vitamins, primarily involved in calcium and phosphorus homeostasis maintenance and in the mineralization Nutrients 2020, 12, 1798; doi:10.3390/nu12061798 www.mdpi.com/journal/nutrientsNutrients 2020, 12, 1798 of bone [1]
Low levels of vitamin D have been associated with solid and non-solid cancer risk, development and growth [5,6,7,8], and vitamin D supplementation in cancer patients has been associated with a favorable prognosis [9,10,11,12,13,14]
D and cancer, this review mainly focuses on the role of vitamin D in a subgroup of solid tumors
Summary
The term vitamin D is referred to liposoluble steroid hormones wrongly qualified as vitamins, primarily involved in calcium and phosphorus homeostasis maintenance and in the mineralization Nutrients 2020, 12, 1798; doi:10.3390/nu12061798 www.mdpi.com/journal/nutrients. Calcitriol is the hormone active form binding to the specific nuclear vitamin D receptor (VDR), which classically regulates gene expression by binding to DNA promoter sequences [2]. In addition to these classic genomic effects, vitamin D could exert its action by non-genomic mechanisms characterized by rapid activation of intracellular signaling molecules, which may include kinases, lipases, second messengers and Ca2+ and Cl- channels, depending on cell type and condition [3]. Vitamin D anticancer actions are carried out through several mechanisms, such as inhibition of proliferation, induction of apoptosis and autophagic cell death and suppression of angiogenesis, demonstrating that vitamin D can have a crucial role in tumor suppression [15]. The review briefly reports the results of the epidemiological evidence linking endogenous levels of vitamin D and supplemented vitamin D doses to cancer risk, cancer development and growth
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