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Reduced isoflavone metabolites formed by the human gut microflora suppress growth but do not affect DNA integrity of human prostate cancer cells

Published online by Cambridge University Press:  19 February 2008

Marian Raschke ,
Kristiina Wähälä  and
Beatrice L. Pool-Zobel
Marian Raschke
Affiliation:
Institute for Nutritional Sciences, Department of Nutritional Toxicology, Friedrich-Schiller-University, Dornburger Strasse 25, 07743 Jena, Germany
Kristiina Wähälä
Affiliation:
Department of Organic Chemistry, University of Helsinki, A.I. Virtasen aukio 1, FIN-00014 Helsinki, Finland
Beatrice L. Pool-Zobel*
Affiliation:
Institute for Nutritional Sciences, Department of Nutritional Toxicology, Friedrich-Schiller-University, Dornburger Strasse 25, 07743 Jena, Germany
*
*Corresponding author: Professor Dr Beatrice L. Pool-Zobel, fax +49 3641 949672, email b8pobe@uni-jena.de
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Abstract

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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. 17β-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) 39·7μmo/, 37·2μmo/) and by equol (IC50 53·8μmo/, 35·1μmo/). O-desmethylangolensin inhibited the growth of LAPC-4 cells (IC50 45·2μmo/), 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.

Keywords

IsoflavonesProstate cancerCell growthDNA damage

Information

Type
Research Article
Information
British Journal of Nutrition , Volume 96 , Issue 3 , September 2006 , pp. 426 - 434
Copyright
Copyright © The Nutrition Society 2006

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