Vitamin D3 Fights Cancer by Activating a Tumor Suppressor Gene

Cancer researchers have determined the molecular basis for the antitumor action of the active form of vitamin D3, 1-alpha,25-dihydroxyvitamin D3 (calcitriol).

While the mode of action of this form of vitamin D3 is not completely understood, investigators have interpreted the results of transcriptomatic studies (evaluation of cellular mRNA expression) carried out on a human colon cancer cell line as showing that vitamin D3 directly activated the gene for cystatin D (CST5).

Cystatin D is a member of the cystatin superfamily of endogenous inhibitors of endosomal/lysosomal cysteine proteases. Cystatins have been reported to play a role in diverse biological processes, including cell proliferation, differentiation, survival, migration, and interleukin and nitric oxide production. Cystatin D has a more restricted pattern of tissue expression and a narrower inhibitory profile than other cystatins: it inhibits cathepsin S, H, and L but not cathepsin B.

In the current study, investigators at the Universidad Autónoma de Madrid (Spain) and the Universidad de Oviedo (Spain) investigated the regulation and biological activity of the CST5 gene in colon cancer. In their report, which was published in the July 6, 2009, issue of the Journal of Clinical Investigation, they presented evidence that vitamin D3 was linked to the direct transcriptional regulation of the human CST5 gene in colon cancer cells. Their results also showed that cystatin D profoundly affected the cell phenotype, inhibiting proliferation and migration and increasing cell adhesiveness.

Experiments where the expression of cystatin D was "knocked down" showed that human colon cancer cells lacking this activity were unresponsive to the antiproliferative effects of the active form of vitamin D3.

The authors concluded the study by saying, "CST5 is a candidate tumor suppressor gene, and it mediates a large proportion of the anticancer effects of the active form of vitamin D3. These data provide rationale for clinical trials examining the preventive and therapeutic potential of the active form of vitamin D3 in colon cancer."

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Universidad Autónoma de Madrid
Universidad de Oviedo