Vitamin D is a fat-soluble vitamin that helps the body absorb calcium and maintain proper calcium and phosphate levels in blood. Vitamin D can also regulate cell growth and differentiation -- the process by which cells acquire specialized functions. Studies on cells derived from human breast cancers have illuminated the many mechanisms by which vitamin D limits the growth of breast cancers.
Vitamin D Sources
Vitamin D is a pro-hormone -- a precursor that becomes a hormone upon activation within the body. The major forms of vitamin D relevant to human health are vitamin D-2, or ergocalciferol, which is made by plants, and vitamin D-3, or cholecalciferol, which is made in the epidermal layer of skin upon exposure to ultraviolet-B rays in sunlight. Cholecalciferol can also be found in fatty fish, fish liver oils and eggs. Some foods, such as milk, are fortified with vitamin D.
Mechanism of Action
Vitamin D, either synthesized in skin or from ingested food, is modified in the liver and kidneys to calcitriol. Calcitriol is the most potent form of vitamin D. Vitamin D is bound by a protein called Vitamin D Receptor, or VDR, within cells. Vitamin D-bound VDR then binds to specific sites on chromosomal DNA -- the genetic material in human cells -- and interacts with other proteins in the cell to turn on or turn off the production of specific proteins that affect many functions, including bone development, calcium absorption and cell growth.
Effects on Breast Cancer
Laboratory studies on breast cancer cells reviewed in the March 2002 issue of "Endocrine-related Cancer" and the July 2003 issue of "The Journal of Nutrition" showed that vitamin D and vitamin D-like compounds inhibit cell growth by inhibiting signals driving either proliferation or survival. Vitamin D compounds also interfere with breast cancer cell growth stimulated through growth factors -- proteins that are made and secreted by cells in the body that regulate cell division and survival. In addition, vitamin D compounds can also inhibit tumor invasion and metastases -- spreading of tumor cells beyond the layer of tissue where it originated and into other parts of the body -- as well as angiogenesis -- growth of new blood vessels.
Clinical Implications
The discovery that vitamin D compounds affect many steps in tumor development and that VDR is present in a majority of breast cancers has generated interest in developing them as clinical aids in cancer management. Results from population-based studies, such as the 2008 meta-analysis published in the "The Journal of Steroid Biochemistry and Molecular Biology," which found that women with the highest vitamin D intakes had the lowest breast cancer risk, have added support for the potential of vitamin D in cancer therapy.
Clinical studies assessing the efficacy of vitamin D and related compounds in breast cancer are under way as of the time of publication. One clinical trial at the Columbia University Medical Center in New York is evaluating the effect of supplementation with high doses of vitamin D on breast cancer development in high-risk post-menopausal women. Results from such trials will help clarify the utility of vitamin D in treatment regimens for breast cancer.
References
- "Endocrine-related Cancer"; Mechanisms Implicated in the Growth Regulatory Effects of Vitamin D in Breast Cancer; Kay W. Colston and Christina M. Hansen; March 2002
- "The Journal of Nutrition"; Vitamin D-3 Receptor as a Target for Breast Cancer Prevention; JoEllen Welsh, et al.; July 2003
- National Cancer Institute: Vitamin D and Cancer Prevention
- Linus Pauling Institute; Micronutrient Information Center; Jane Higdon, Ph.D.; March 2004
- "Molecular Cancer Therapeutics"; Promise of Vitamin D Analogues in the Treatment of Hyperproliferative Conditions; Sonoko Masuda and Glenville Jones; April 2006
- "The Journal of Steroid Biochemistry and Molecular Biology"; Intake of Vitamin D and Risk of Breast Cancer: a Meta-Analysis;Tina Gissel, et al.; September 2008
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