Vitamin D in cancer chemoprevention

Abstract

Context: There is increasing evidence that Vitamin D (Vit D) and its metabolites, besides their well-known calcium-related functions, may also exert antiproliferative, pro-differentiating, and immune modulatory effects on tumor cells in vitro and may also delay tumor growth in vivo. Objective: The aim of this review is to provide fresh insight into the most recent advances on the role of Vit D and its analogues as chemopreventive drugs in cancer therapy. Methods: A systematic review of experimental and clinical studies on Vit D and cancer was undertaken by using the major electronic health database including ISI Web of Science, Medline, PubMed, Scopus and Google Scholar. Results and conclusion: Experimental and clinical observations suggest that Vit D and its analogues may be effective in preventing the malignant transformation and/or the progression of various types of human tumors including breast cancer, prostate cancer, colorectal cancer, and some hematological malignances. These findings suggest the possibility of the clinical use of these molecules as novel potential chemopreventive and anticancer agents.

Analysis of the interaction of calcitriol with the disulfide isomerase ERp57

“…demonstrate that Denosomin-Vitamin D3 hybrids, used as anti-Alzheimer’s disease agents, exhibit nerve re-extension activity in Aβ-damaged neurons via the ERp57 (1,25D3-MARRS) pathway. Considering also the role of ERp57 in important cellular functions and the promising clinical use of vitamin D analogues in prevention or therapy in several types of malignancies54, the interaction between these two molecules is of sure interest and would need further investigations in the cellular context.…”

Effects of supplemental calcium and vitamin D on tight‐junction proteins and mucin‐12 expression in the normal rectal mucosa of colorectal adenoma patients

“…There is strong animal experimental and generally supportive human observational evidence for protection against CRC by calcium and vitamin D .…”

“…[15][16][17] There is strong animal experimental and generally supportive human observational evidence for protection against CRC by calcium and vitamin D. [18][19][20] Proposed mechanisms include calcium and vitamin D's direct effects on cell proliferation, differentiation, and apoptosis; vitamin D's modulation of inflammation, growth factor signaling, androgen and estrogen receptor pathways, immune function, and angiogenesis; and calcium's ability to bind DNA-damaging/cytotoxic bile acids and fatty acids in the stool, thereby reducing mutations, oxidative stress, inflammation, and proliferation. 18,20 Recent evidence indicates that calcium and vitamin D may also be involved in maintaining the integrity of the intestinal mucosal barrier. 21,22 The vitamin D receptor (VDR) was found to play an important role in mucosal barrier function by preserving the integrity of epithelial junction complexes and increasing the mucosal regeneration and healing capacity of the colonic epithelium.…”

Exploring vitamin D signalling within skin cancer

“…Vitamin D not only suppresses cancer cells and cancer stem cells, but also regulates the tumour microenvironment. Several studies suggest that vitamin D can regulate tumour initiation and metastasis by influencing cell‐microenvironment interactions . Tumour cells along with a small proportion of cancer stem cells exist in a stromal microenvironment consisting of vasculature for nourishment, cancer‐associated fibroblasts, immune cells and extracellular components.…”

“…Several studies suggest that vitamin D can regulate tumour initiation and metastasis by influencing cell-microenvironment interactions. 38 Tumour cells along with a small proportion of cancer stem cells exist in a F I G U R E 3 Vitamin D, DDIT4 and mTORC1 communication in the DNA damage response. (A) Classically, low energy DNA damage activates ATM/ATR and CHK1/CHK2 kinases leading to phosphorylation, stabilization and activation of the tumour suppressor p53.…”