The influence of isoflavonoids on the antitumor activity of vitamin D3

Isoflavonoids exert a regulatory function on the expression of cytochrome P450 enzymes and also up-regulate the vitamin D(3) receptor (VDR) on cancer cells, which increase their sensitivity to 1,25-dihydroxyvitamin D(3) , the hormonally active form of vitamin D(3) . Isoflavonoids are also able to raise the serum level of the active form of vitamin D(3) due to their inhibitory activity on CYP24, the enzyme involved in the degradation of 1,25-dihydroxyvitamin D(3) and its precursor 25-OH-D(3) to inactive compounds. Another enzyme, CYP27B1, involved in the synthesis of 1,25-dihydroxyvitamin D(3) , is stimulated by isoflavonoids, and this may result in a similar effect of increasing in the serum level of 1,25-dihydroxyvitamin D3. CYP27B1 and CYP24 were found in kidneys (the main location of 1,25-(OH) (2)D(3) synthesis) and also in brain cells, osteoclasts, keratinocytes, macrophages, intestine epithelial cells, and in some cancer cells. The expression of VDR was detected not only in the cells primarily targeted by 1,25-dihydroxyvitamin D3, but also in epithelial and mesenchymal cells. Therefore, combined treatment with isoflavonoids and 1,25-dihydroxyvitamin D3 might be effective in both cancer prevention and treatment.