Study sheds light on vitamin D's anti-cancer properties

A new EU-funded study increases our understanding of vitamin D's apparent anti-cancer properties. The findings support the need for further clinical trials examining the potential of the active form of vitamin D3 to prevent and treat colon cancer.

The findings are published online in the Journal of Clinical Investigation. EU support for the work came from the NUCSYS ('Systems biology of nuclear receptors: A nutrigenomics approach to aging-related diseases') project, which is funded under the 'Human resources and mobility' Activity area of the Sixth Framework Programme (FP6), and the MICROENVIMET ('Understanding and fighting metastasis by modulating the tumour microenvironment through interference with the protease network') project, which is financed through the Health Theme of the Seventh Framework Programme (FP7).

Over 400,000 people are diagnosed with colorectal cancers every year in Europe, and it is the second most common cancer in women and the third most common cancer in men. It kills over 200,000 people every year, making it the second biggest cause of cancer deaths in men and women.

A number of studies have indicated that the active form of vitamin D3 may have significant anti-cancer properties. Earlier studies on human colon cancer cell lines have shown that activity levels of a gene called CST5 may be affected by the active form of vitamin D3. CST5 is responsible for making a protein called cystatin D.

In this latest study, Spanish researchers studied this protein in greater detail. Their investigations reveal that cystatin D has important tumour-suppressing properties, and that it is the mechanism through which vitamin D3 affects cancer cells.

"These results contribute to explain the higher susceptibility to colon cancer caused by vitamin D deficiency in animal models and the results of epidemiological and clinical studies that indicate antitumoural action of vitamin D in humans," the researchers write.

Firstly, the researchers established that the active form of vitamin D3 directly activates the CST5 gene in human colon cancer cell lines. This increases the levels of the cystatin D protein in the cells.

It turns out that the cystatin D protein blocks the growth of human colon cancer cell lines both in the test tube and in mice. Artificially reducing the activity of the CST5 gene renders cells unresponsive to the anti-cancer effects of vitamin D.

The exact mechanisms by which cystatin D exerts control over cancer cells remain unclear. Nevertheless, the researchers conclude: "Together, our findings reveal an unpredicted activity of CST5 as a tumour suppressor. Furthermore, our results illustrate what we believe to be a novel mechanism of the anticancer action of the most active vitamin D metabolite and provide a rationale for its preventive and therapeutic use against colon cancer."

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