Vitamin D in Cancer Prevention and Treatment: A Review of Epidemiological, Preclinical, and Cellular Studies

• Published in: Cancers Vol. 16; no. 18; p. 3211
• Main Authors: Dallavalasa, Siva, Tulimilli, SubbaRao V, Bettada, Vidya G, Karnik, Medha, Uthaiah, Chinnappa A, Anantharaju, Preethi G, Nataraj, Suma M, Ramashetty, Rajalakshmi, Sukocheva, Olga A, Tse, Edmund, Salimath, Paramahans V, Madhunapantula, SubbaRao V
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20-09-2024; MDPI
• Subjects: Alfacalcidol; Analysis; Angiogenesis; Antitumor activity; Apoptosis; Calcifediol; Cancer; Cancer therapies; Cell cycle; Cell migration; Cell proliferation; Chemotherapy; Chromosomes; Clinical trials; Colorectal cancer; Dietary supplements; Disease prevention; Drug resistance; Enzymes; Epidemiology; Genes; Hyperglycemia; Kinases; Metabolism; Metabolites; Metastases; Mortality; Neuroblastoma; Oncology, Experimental; Physiology; Prevention; Proteins; Radiation; Receptor mechanisms; Review; Reviews; Vitamin D; Vitamin D receptors; Vitamin deficiency; Xenografts; India; VDR polymorphism; vitamin D analogs; cell cycle; metastasis; vitamin D; apoptosis; cancer; vitamin D receptor
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers16183211

Inhibition of human carcinomas has previously been linked to vitamin D due to its effects on cancer cell proliferation, migration, angiogenesis, and apoptosis induction. The anticancer activity of vitamin D has been confirmed by several studies, which have shown that increased cancer incidence is associated with decreased vitamin D and that dietary supplementation of vitamin D slows down the growth of xenografted tumors in mice. Vitamin D inhibits the growth of cancer cells by the induction of apoptosis as well as by arresting the cells at the G0/G1 (or) G2/M phase of the cell cycle. Aim and Key Scientific Concepts of the Review: The purpose of this article is to thoroughly review the existing information and discuss and debate to conclude whether vitamin D could be used as an agent to prevent/treat cancers. The existing empirical data have demonstrated that vitamin D can also work in the absence of vitamin D receptors (VDRs), indicating the presence of multiple mechanisms of action for this sunshine vitamin. Polymorphism in the VDR is known to play a key role in tumor cell metastasis and drug resistance. Although there is evidence that vitamin D has both therapeutic and cancer-preventive properties, numerous uncertainties and concerns regarding its use in cancer treatment still exist. These include (a) increased calcium levels in individuals receiving therapeutic doses of vitamin D to suppress the growth of cancer cells; (b) hyperglycemia induction in certain vitamin D-treated study participants; (c) a dearth of evidence showing preventive or therapeutic benefits of cancer in clinical trials; (d) very weak support from proof-of-principle studies; and (e) the inability of vitamin D alone to treat advanced cancers. Addressing these concerns, more potent and less toxic vitamin D analogs have been created, and these are presently undergoing clinical trial evaluation. To provide key information regarding the functions of vitamin D and VDRs, this review provided details of significant advancements in the functional analysis of vitamin D and its analogs and VDR polymorphisms associated with cancers.