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Selenium, isoflavones, and AR‐regulated genes in rat prostate
Author(s) -
Legg Russell,
Tolman Jessica,
Lovinger Cameron,
Lephart Edwin,
Setchell Kenneth,
Christensen Merrill
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a106-a
Subject(s) - isoflavones , daidzein , genistein , equol , endocrinology , medicine , prostate cancer , phytoestrogens , androgen receptor , chemistry , biology , cancer , estrogen
This study aimed to identify potential prostate cancer chemopreventive effects of combined high intake of Se and isoflavones. Subjects were Noble male rats born to breeders fed stock diets containing low (10 ppm) or high (600 ppm) isoflavones, with or without a supplement of 3 ppm Se as Se‐methylselenocysteine. Pups continued consuming the same diets as their parents until sacrifice at 200 days. Liver glutathione peroxidase activity was unaffected by diets. Serum isoflavone (equol+genistein+daidzein) concentrations averaged 23.5 + 2.4 ng/ml (mean + SD) in rats fed 10 ppm isoflavones, and 1457 + 273 ng/ml in rats fed 600 ppm diets. Dietary Se had no effect on serum isoflavones. Steady state mRNA levels in dorsolateral prostates were determined for genes which previous data mining (Zhang 2005) showed to be 1) differentially regulated in prostate cancer; 2) androgen receptor (AR)‐regulated; and 3) for which high Se countered AR effects. These genes included Abcc4, Dhcr24, Ascl3, and Gucyla3. Levels of mRNA for Akr1c6 and AR (large) were also assayed. High isoflavones decreased expression of Akr1c6, Ascl3, and Gucy1a3 (p=.000–.003). High Se decreased expression of AR, Abcc4, and Dhcr24 (p=.000–.012). Combined intake of high Se and high isoflavones may achieve a greater chemopreventive effect that either compound supplemented individually. (Supported by NIH CA122235).