Table of contents
- Repurposing vitamin D for treatment of human malignancies via targeting tumor microenvironment – March 2019
- Stem Cells - What are they and why are they important (to Multiple Sclerosis) 2019?
- Vitamin D can be used as a supplement against cancer stem cells - Sept 2018
- Boosting the effects of vitamin D to tackle diabetes - May 2018 Stem Cells Portal
- How Vitamin D Stops Cancer Stem Cells - 2016?
- Vitamin D Raises Number of Blood Stem Cells During Development - 2016
- See also VitaminDWiki
Repurposing vitamin D for treatment of human malignancies via targeting tumor microenvironment – March 2019
Tumor cells along with a small proportion of cancer stem cells exist in a stromal microenvironment consisting of vasculature, cancer-associated fibroblasts, immune cells and extracellular components. Recent epidemiological and clinical studies strongly support that vitamin D supplementation is associated with reduced cancer risk and favorable prognosis. Experimental results suggest that vitamin D not only suppresses cancer cells, but also regulates tumor microenvironment to facilitate tumor repression. In this review, we have outlined the current knowledge on epidemiological studies and clinical trials of vitamin D. Notably, we summarized and discussed the anticancer action of vitamin D in cancer cells, cancer stem cells and stroma cells in tumor microenvironment, providing a better understanding of the role of vitamin D in cancer. We presently re-propose vitamin D to be a novel and economical anticancer agent.
“Supplementation of vitamin D is associated with reduced cancer risk and favorable prognosis. Vitamin D not only suppresses cancer cells and cancer stem cells, but also regulates tumor microenvironment, demonstrating the promise of the benefit of vitamin D in cancer prevention and treatment.”
Cancer stem cells (CSCs) or tumor initiating cells (TICs) are critically responsible for tumorigenesis, progression, metastasis, and tumor recurrence, but they account for only a small proportion of cancer cells. Regarding the important role of the low-proportion CSCs in cancer microenvironment, targeting CSCs might be an efficient and promising method for cancer suppression. Recent studies have demonstrated that vitamin D may suppress cancer progression through targeting CSCs compartment. The role of vitamin D in regulating CSCs in gastrointestinal cancers has been thoroughly reviewed in our previous report179. Here we further summarized the suppressive action of vitamin D on CSCs in other cancers such as breast and prostate cancers.
In breast cancer, CD44 was identified as a breast cancer stem cell marker and CD44+/CD24-/low cells and CD49f+/CD24-/low were identified as tumor-initiating cells180. In MCF10A ductal carcinoma in situ (DCIS) cells, CD44 was significantly down-regulated by a Gemini vitamin D analog, BXL1024180. BXL1024 reduced the breast cancer stem-like cells population including CD44+/CD24-/low and CD49f+/CD24-/low subpopulation of MCF10A DCIS cells, and suppressed the stem cell markers expression (CD44 and CD49f)180. Further study has shown that the suppressive effect of 1,25(OH)2D3 or its analogue on breast CSCs in MCF10A DCIS was dependent in Hes1-mediated inhibition of Notch signaling181. In mammosphere, OCT4 and KLF4, which is associated with stem cell self-renewal and undifferentiated phenotype, were reduced by 1,25(OH)2D3 or BXL1024182. It is reported that another vitamin D analogue EB1089 in cooperation with BRAC1 exhibited anti-mammosphere formating ability in breast cancer cells183. Notably, Jeong et al.184 found that 1,25(OH)2D3 or oral administration with vitamin D could inhibit mouse TICs in MMTV-WNT1 mammary tumors through WNT//I- catenin signaling in vivo. 1,25(OH)2D3 inhibited spheroids formation of mouse TICs in 3D tumor spheroid culture assay in vitro1184. However, some studies showed that VDR was down-regulated in breast cancer mammosphere, potentially indicating less vitamin D action on breast CSCs183’185. Despite the controversy, the current findings still provided a new strategy for vitamin D targeting breast CSCs and give us a deeper understanding of vitamin D effect in cancer.
Although the anticancer effect of vitamin D on prostate cancer cells has been widely explored both in vitro and in vivo, the exact pharmacological action of vitamin D on prostate CSCs is not well understood. Existing evidence showed that the mechanism involved in the regulation of prostate CSCs by vitamin D was partly similar to that of prostate cancer cells. Maund et al.186 demonstrated that 1,25(OH)2D3 could induce p21 and p27 expression as well as cell cycle arrest in mouse prostate CSCs, and its anti-proliferative effect was mainly mediated by upregula- tion of IL-1a. In addition, the micro-array data indicated that the CSCs signaling (e.g., BMP and TGF-) participated in the regulatory action of 1,25(OH)2D3 on prostate CSCs186. Taken together, the mechanisms underlying vitamin D regulation of CSCs seem similar to that of normal cancer cells, i.e., mainly through WNT/-catenin, BMP, Notch and TGF- signaling mechanisms.
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- Sun H, Wang C, Hao M, Sun R, Wang Y, Liu T, et al. CYP24A1 is a potential biomarker for the progression and prognosis of human colorectal cancer. Hum Pathol 2016;50:101-8.
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- Luo W, Yu WD, Ma Y, Chernov M, Trump DL, Johnson CS. Inhibition of protein kinase CK2 reduces Cyp24a1 expression and enhances 1,25-dihydroxyvitamin D3 antitumor activity in human prostate cancer cells. Cancer Res 2013;73:2289-97.
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- Izkhakov E, Somjen D, Sharon O, Knoll E, Aizic A, Fliss DM, et al. Vitamin D receptor expression is linked to potential markers of human thyroid papillary carcinoma. J Steroid Biochem Mol Biol 2016;159:26-30.
- Khadzkou K, Buchwald P, Westin G, Dralle H, Akerstrom G, Hellman P. 25-hydroxyvitamin D3 1a-hydroxylase and vitamin D receptor expression in papillary thyroid carcinoma. J Histochem Cytochem 2006;54:355-61
National MS Society
Many videos and studies
Cell Mol Biol (Noisy-le-grand). 2018 Sep 30;64(12):47-51. PMID: 30301502
Koçak N1, Nergiz S1, Yıldırım İH2, Duran Y1.
Cancer is standing like a bottomless pit or a black hole in front of mankind. Scientists are trying all possible ways to find a solution against to cancer. As known, cancer is a phenomenon fed from internal dynamics. One of internal dynamic is cancer stem cells that are involved in the formation and development of cancer. Because of these dynamics, scientists began to search solution inside of the body. Another internal dynamic is vitamin D and it is not only important in calcium homeostasis but also it is important for cell proliferation, differentiation, and apoptosis. In this study, we investigated the effect of vitamin D on cancer stem cells that sorted from MCF-7 cell line and on HEK293 cell line as control. Our results showed that calcitriol treatment reduced the number of CSC (Cancer Stem Cell) in the MCF-7 cell while increased in HEK293 cell population. Gene expression analyses showed that effect of calcitriol on apoptosis plays an important role in this reduction. Deficiency or unavailability of vitamin D may take a role in the pathogenesis of breast cancer.
- "In a paper published May 10 in Cell, researchers from the Salk Institute report a potential new approach for treating diabetes by protecting beta cells — the cells in the pancreas that produce, store and release the hormone insulin. When beta cells become dysfunctional, the body can't make insulin to control blood sugar (glucose) and levels of glucose can rise to dangerous, even fatal levels."
- "The investigators accomplished their goal by using an unexpected source: vitamin D. Vitamin D in cells and mouse models proved beneficial in treating damaged beta cells. It also provided new insights about gene regulation that could be applied to developing treatments for other diseases, including cancer."