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A Review of the Role Portrayed by Vitamin D in Cancer

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A Review of the Role Portrayed by Vitamin D in Cancer Cancer Therapy & Oncology International Journal ISSN: 2473-554X Review Article Canc Therapy & Oncol Int J Volume 11 Issue 2 - June 2018 Copyright © All rights are reserved by Kiran Dahiya DOI: 10.19080/CTOIJ.2018.11.555807 A Review of the Role Portrayed by Vitamin D in Cancer Rakesh Dhankhar1, Kiran Dahiya2*, Raunak Ahlawat3, Priya Dahiya4, Sunder Singh1 and Keerti Gupta2 1Department of Radiotherapy, Pt. BD Sharma PGIMS, Rohtak, Haryana, India 2Department of Biochemistry, Pt. BD Sharma PGIMS, Rohtak, Haryana, India 3Ex-student, BPSGMCW, Khanpur Kalan, Sonepat, Haryana, India 4Department of Obstetrics and Gynecology, Rajshree Medical Research Institute, Bareilly, Uttar Pradesh, India Submission: May 07, 2018; Published: June 25, 2018 *Correspondence Address: Kiran Dahiya, Professor, Department of Biochemistry, Pt. BD Sharma PGIMS, Rohtak, Haryana, India, Tel: ; Email: Abstract homeostasis in the body and taking care of the bone health, it performs a number of important functions in the body. It can be synthesized by Vitamin D, also known as calcitriol, is not only one of the fat soluble vitamins but is a versatile hormone. Besides taking part in calcium D the body in presence of sunlight as well as can be derived from few dietary sources. Recently2 it has been observed that deficiency of vitamin D is rampant in general population around the world. Deficiency of vitamin D [1,25-(OH) 3] has now been associated with a variety of clinical diseases including cancer. Though the exact mechanism involved is not clear yet, a number of theories have been put forward for the role played by vitamin D in protection against cancer. For this effect, important actions include anti-inflammatory, anti-proliferative, anti-angiogenic and effectpro-apoptotic associated. which But are further able researchto abet cancer is still at needed any stage. to establish Anti-cancer all the action claims. of vitamin D is seen in prevention of all the stages of carcinogenesis. It helps to improve the efficacy of chemotherapy as well as radiotherapy in the treatment while helping in minimizing or avoiding the adverse Keywords: Vitamin D; Anti-cancer activity; Anti-proliferative; Anti-inflammatory; Pro-apoptotic; Radiosensitization Introduction There is a recent surge in the interest of estimating, analyzing rough estimate indicates that about 1 billion people globally are both cutaneous synthesis and dietary sources of vitamin D. A disorders. Vitamin D, a fat-soluble vitamin, is considered a and associating vitamin D deficiency with a variety of clinical prohormone because the body can synthesize vitamin D from vitamin D deficient and vitamin D deficiency is quite common in regions and countries including North America, Northern Europe, Saudi Arabia, United Arab Emirates, Australia, Turkey, its precursor (cholesterol) when exposed to ultraviolet light at phosphorus levels in the body, a variety of diverse functions have India and Lebanon [3] Besides the regulation of calcium and a wavelength between 290-315 nm. Active form of vitamin D [1,25-(OH) D is 1,25-dihydroxy2 cholecalciferol/ 1,25-dihydroxy vitamin D3 to be implicated in a number of clinical chronic disorders like ubiquitous nuclear3 vitamin D receptor (VDR) to regulate the been assigned to vitamin D. Therefore, its deficiency is bound ] or calcitriol. This metabolite interacts with its heart disease, bone disorder, cancer, infectious, inflammatory transcription of a wide spectrum of genes involved in calcium differentiation. It is these latter actions that have attracted tumor and autoimmune diseases, inflammatory bowel disease, multiple and phosphate homeostasis as well as in cell division and sclerosis, rheumatoid arthritis and type-I diabetes mellitus etc. [3]. antiproliferative agent in cancer cells in vitro and in vivo [1]. Many mechanisms have been put forward for its role in causation biologists to explore the effects of vitamin D and to use it as an of different disorders but this review has been targeted to throw development of cancer. The general aspects pertaining to its be maintained for normal functioning of all the systems of the body some light on the association between vitamin D deficiency and Adequate circulating levels of active form of this vitamin need to affect any system and produce the related clinical abnormality [2]. metabolism and assessment will be discussed first. irrespective of age and gender. Insufficient levels of vitamin D may Discussion Metabolism of vitamin D Lately, the scientific evidence is accumulating to demonstrate the insufficiency of vitamin D globally. Factors, which play a crucial among countries; but in all cases involve limitations in either or The major sources for vitamin D include sun exposure role in the worldwide prevalence of vitamin D insufficiency, vary (predominant source), foods like fatty fish, beef liver, cheese, Canc Therapy & Oncol Int J 11(2): CTOIJ.MS.ID.555807 (2018) 001 Cancer Therapy & Oncology International Journal egg yolk, cod liver oil and mushrooms etc. [4] Vitamin D can be 3 derived by irradiation of plant sterols/ ergosterol. Initially, the two or be derived in the form of vitamin D or vitamin D (collectively synthesized in the skin from the precursor 7-dehydroxycholesterol2 forms of the vitamin were considered to be interchangeable and serum 25(OH)D as an indicator of vitamin D functional status, it 3 equivalent, however, since the availability of the measurement of metabolites are mostly hydrophobic and thus require a protein has become clear that vitamin D is substantially less potent than known as vitamin D) from dietary sources. Vitamin D and its 3 2 (vitamin D–binding protein) for their transport in the aqueous vitamin D environment of the bloodstream to sites of storage (adipose tissue) 3. These two seem to be absorbed from the intestine and or sites of activation (liver and kidney) or sites of action. Vitamin vitamin D to be 25-hydroxylated2 in the liver with equal efficiency; however, to increased metabolic degradation of both the administered D seems to up regulate several 24-hydroxylases, leading2 in the liver, a step carried out by and endogenous D . Thus, although it is certainly possible to treat D undergoes its first step of activation with help of 25-hydroxylase , ergocalciferol seems to to produce 25-hydroxy vitamin D3 3 2 have no advantage over vitamin D both liver mitochondrial (CYP27A1) and microsomal cytochrome patients satisfactorily with vitamin D P450 isoforms CYP2R1,CYP3A4, and CYP2J3 [5-7]. , is 3 (cholecalciferol), which is the activated to the hormonal form, 1,25-(OH) D , primarily in3 the naturalVitamin form D and of the Cancer vitamin and is less expensive [16-19]. The circulating metabolite, 25-hydroxyvitamin2 D 3 2D kidney. Patients with chronic renal failure exhibit frank rickets Vitamin D deficiency is known principally for its association or osteomalacia due to a deficiency of circulating 1,25-(OH) 3 risk of several types of cancer is receiving considerable attention of the 1 with bone disorders, but its newly recognized association with caused by lack of renal 1α-hydroxylase [8,9]. The main component D α-hydroxylase enzyme is the cytochrome P450, CYP27B1,2 and up-regulated by parathyroid hormone (PTH) as part of the3 [20-22]. The high prevalence of vitamin D deficiency, combined which is strongly down-regulated by its product, 1,25-(OH) with the discovery of increased risks of certain types of cancer may account for several thousand premature deaths from colon, in those who are deficient, suggests that vitamin D deficiency calcium homeostatic loop and up-regulated by fibroblast-like [10,11]. growth factor 23 as part of the phosphate homeostatic loop breast, ovarian and prostate cancer annually [23,24]. Vitamin D Assessment of vitamin D Levels of cancer. The vitamin D receptor (VDR) is essential to initiate deficiency has been found to be associated with different stages Though 1,25(OH)2D is the active form of vitamin D but 25(OH) 3 D is the predominantly 3analyzed form. It is because of the fact that various signaling pathways that are induced by 1,25(OH)2D cancer activity. There are several reports suggesting that VDR serum3 25(OH)D is the major circulating form of vitamin D and and have been shown to play a substantial role in its anti- 3 2 has a circulating half-life of 4 hours and a concentration 1,000 expression is gradually reduced when the stage of malignancy has a half-life of 2 to 3 weeks compared with 1,25(OH) D, which advances and certain VDR polymorphisms are associated with locally circulating 25(OH)D can be converted into 1,25(OH)2D increased cancer risk [25,26]. It has also been reported that times lower than that of 25(OH)D. Besides, vitamin D deficiency D . 3 3 is associated with a compensatory increase of PTH secretion,2 3 by the enzyme 25-hydroxyvitamin D-1α-hydroxylase (CYP27B1), which stimulates the kidneys to produce more 1,25(OH) such as colon, breast, prostate, placenta and different cells of concentrations of 1,25(OH)3 D which is not only expressed in kidney but in many other tissues Thus, when 25(OH)D levels2 fall due to vitamin D deficiency, the the immune system suggesting the role played by these tissues and in some cases, they might even be elevated. In suspected renal 3 may remain within normal limits in the metabolism of vitamin D [27]. The anti-cancer activities impairment and inherited disorders of 25(OH)D and phosphate of 1,25(OH)2D metabolism, both 25(OH)D and 1,25(OH)2D should3 be measured. 3 There are multiple assays available3 to measure3 25(OH)D include the effects of its local synthesis, which as endocrine actions of circulating 1,25(OH)2D great variability in results. Therefore, treatment should3 target a induces autocrine/ paracrine actions within the tumors as well but with goal above normal reference levels (Table 1) to ensure adequate 3 [28].
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