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., and Madhunapantula, SubbaRao V.
Simple Summary: Inhibition of human cancers has previously been linked to the administration of vitamin D. Studies have shown that increased cancer incidence is associated with decreased vitamin D. The anticancer activity of vitamin D has been confirmed by several in vitro and in vivo studies. Vitamin D inhibits the growth of cancer cells by (a) the induction of apoptosis, (b) decreasing the metastatic spread, (c) arresting the cells at the G0/G1 (or) G2/M phase in the cell cycle, and (d) downregulating proliferation signals. Supplementation of vitamin D slows down the growth of xenografted tumors in mice. Hence, vitamin D could be considered a potential cancer chemotherapeutic agent. Background: 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. [ABSTRACT FROM AUTHOR]