Regulation of extrarenal synthesis of 1,25-dihydroxyvitamin D3-relevance for colonic cancer prevention and therapy

Epidemiological studies have demonstrated a high incidence of colonic tumors in populations living in areas of low sunlight exposure. This suggests 1,25-dihydroxyvitamin D3, an antimitotic prodifferentiating steroid hormone, as a potentially preventive factor since levels of the precursor 25-hydroxyvitamin D3 in serum are, to a major part, dependent upon sun exposure. Conversion into the active metabolite from the precursor is effected by CYP27B1, and degradation by CYP24. Both P450 hydroxylases are known to be located in the kidney. However, we were able to demonstrate presence, and activity of both enzymes also in the colon. We have shown also that during early tumor progression expression of CYP27B1 and of the vitamin D receptor is upregulated. Therefore the vitamin D system may function as a potent physiological defense against further tumor progression in cancer patients. We suggest that estrogenic substances, and also phytoestrogens present in soy food could, by increasing tumor tissue-located CYP27B1 activity and decreasing degradative CYP24 activity, augment tumor-localized 1,25-dihydroxyvitamin D3 levels and activity. (C) 2003 Elsevier Ltd. All rights