Regulation of extrarenal vitamin D metabolism as a tool for colon and prostate cancer prevention.
Though 1,25-dihydroxyvitamin D3 (1,25-D3) as well as some vitamin D analogs have an antimitotic as well as a differentiating action, therapeutic application in tumor patients is still precluded due to their hypercalcemic action at the necessary concentration. Our observation that early during progression, colon tumor cells express CYP27B1, the enzyme essential for 1,25-D3 synthesis, as well as the vitamin D receptor (VDR) at a higher level than normal colon cells led to the speculation that, by induction of this expression, a physiological defense against tumor progression could be activated and enhanced. In some Asian countries where soy products are a main staple, prostate and breast tumor incidence is extremely low. We speculated that this could be due to regulation of CYP enzymes by phytoestrogens present in soy such as genistein. In prostate tumor cells, the 1,25-dihydroxyvitamin D3 catabolizing enzyme CYP24 is frequently highly expressed. We were able to demonstrate that genistein down-regulates expression of CYP24 to almost nil, which would result in enhancement of local 1,25-D3 levels and improved mitotic control of tumor cells.
Cross
Heide S
HS
Institute of Pathophysiology, University of Vienna Medical School, Währinger Gürtel 18-20, A-1090 Vienna, Austria. heide.cross@akh-wien.ac.at
Kállay
Enikö
E
Farhan
Hesso
H
Weiland
Tina
T
Manhardt
Theresa
T
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism*; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000517:prevention & control*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D004044:Dietary Proteins / Q000008:administration & dosage; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D019833:Genistein / Q000737:chemistry; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology; D008297:Male; D048789:Phytoestrogens; D028321:Plant Preparations / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000517:prevention & control*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D030262:Soybean Proteins / Q000008:administration & dosage / Q000737:chemistry; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism*; D014807:Vitamin D / Q000378:metabolism*; D065668:Vitamin D3 24-Hydroxylase
D004044:Dietary Proteins; D004968:Estrogens, Non-Steroidal; D007529:Isoflavones; D048789:Phytoestrogens; D028321:Plant Preparations; D012333:RNA, Messenger; D030262:Soybean Proteins; D014807:Vitamin D; D003577:Cytochrome P-450 Enzyme System; D019833:Genistein; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase