Reduced isoflavone metabolites formed by the human gut microflora suppress growth but do not affect DNA integrity of human prostate cancer cells.
Dietary isoflavones, such as genistein and daidzein, are metabolised by the human gut microflora. Case-control studies have disclosed a link between the formation of the daidzein metabolite equol and prostate cancer risk. We evaluated the effects of genistein, daidzein and five metabolites on two prostate cancer cell lines by determining DNA integrity and cell growth. LNCaP cells contain the T877A androgen receptor mutation whereas Los Angeles prostate cancer (LAPC)-4 cells express the wild-type receptor, both of which may affect responses to isoflavones. DNA integrity was determined using the comet assay. Cell growth was assessed by staining DNA with 4',6'-diamidino-2-pheylindole hydrochloride. Endogenous steroid hormones, but not isoflavones, induced DNA strand breaks. Dihydrotestosterone stimulated the growth of both cell lines. 17beta-Oestradiol increased the growth of LNCaP but not LAPC-4 cells, pointing to an involvement of the T877A androgen receptor. Isoflavones did not stimulate growth in either prostate cancer cell line. However, the growth of LNCaP and LAPC-4 cells was suppressed by genistein (inhibitory concentration 50 % (IC50) 39.7 mumol/l, 37.2 mumol/l) and by equol (IC50 53.8 mumol/l, 35.1 mumol/l). O-desmethylangolensin inhibited the growth of LAPC-4 cells (IC50 45.2 mumol/l), but not of LNCaP cells. In conclusion, isoflavones do not damage DNA or promote growth of androgen-dependent prostate cancer cells. Several isoflavones, including the reduced daidzein metabolites equol and O-desmethylangolensin, suppress cancer cell growth. Taken together, these data suggest a contribution of gut-formed isoflavone metabolites to the beneficial effects of dietary isoflavones on prostate cancer risk.
Raschke
Marian
M
Institute for Nutritional Sciences, Department of Nutritional Toxicology, Friedrich-Schiller-University, Dornburger Strasse 25, 07743 Jena, Germany.
Wähälä
Kristiina
K
Pool-Zobel
Beatrice L
BL
D000728:Androgens / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D020552:Comet Assay / Q000379:methods; D004249:DNA Damage / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects*; D013196:Dihydrotestosterone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D019833:Genistein / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007422:Intestines / Q000382:microbiology*; D007529:Isoflavones / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D048789:Phytoestrogens / Q000378:metabolism / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*
D000728:Androgens; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D007529:Isoflavones; D048789:Phytoestrogens; D013196:Dihydrotestosterone; D004958:Estradiol; C004742:daidzein; D019833:Genistein