Abstract
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, 17,-estradiol and genistein induced CYP27B1 but reduced CYP24 activity, while equol was inactive. Mammary cells express both estrogen receptors (ER) α and,, while colon cells express mainly ER,, 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.
- Synthesizing 25-D3-1α-hydroxylase
- catabolic 25-D3-24-hydroxylase
- cancer prevention
- phytoestrogens
- estrogen receptors
Footnotes
- Received December 29, 2005.
- Accepted February 20, 2006.
- Copyright© 2006 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved