Genistein and 17beta-estradiol, but not equol, regulate vitamin D synthesis in human colon and breast cancer cells.
Extrarenal synthesis of the active vitamin D metabolite 1,25-dihydroxyvitamin-D3 (1,25-D) has been observed in cells derived from human organs prone to sporadic cancer incidence. Enhancement of the synthesizing hydroxylase CYP27B1 and reduction of the catabolic CYP24 could support local accumulation of the antimitotic steroid, thus preventing formation of tumors of e.g., colon and breast. By applying quantitative RT-PCR and HPLC it was observed that in colon-(Caco-2) and breast-(MCF-7) derived cells, 17beta-estradiol and genistein induced CYP27B1 but reduced CYP24 activity, while equol was inactive. Mammary cells express both estrogen receptors (ER) a and beta, while colon cells express mainly ERbeta, possibly explaining why MCF-7 cells were more affected. These results indicate a potential, new approach for cancer prevention by counteraction of the 1,25-D-driven negative feedback, i.e., down-regulation of CYP27B1 and up-regulation of CYP24, which prevents its own local accumulation. However, mammary cells may be more susceptible to this than colonocytes.
Lechner
Daniel
D
Department of Pathophysiology, Medical University of Vienna, Währingergürtel 18-20, A-1090 Vienna, Austria.
Bajna
Erika
E
Adlercreutz
Herman
H
Cross
Heide S
HS
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D018938:Caco-2 Cells; D002117:Calcitriol / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D060754:Equol; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000096:biosynthesis; D047629:Estrogen Receptor beta / Q000096:biosynthesis; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013250:Steroid Hydroxylases / Q000378:metabolism; D065668:Vitamin D3 24-Hydroxylase
C007610:4',7-dihydroxy-3,4-dihydroisoflavone; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D007529:Isoflavones; D012333:RNA, Messenger; D004958:Estradiol; D060754:Equol; D019833:Genistein; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol