Carcinogenesis Advance Access published online on June 13, 2006
Carcinogenesis, doi:10.1093/carcin/bgl082
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1 Department of Nutritional Toxicology, Friedrich-Schiller-University of Jena, Dornburger Strasse 25, 07743 Jena, Germany
* To whom correspondence should be addressed. Prostate cancer is one of the most frequent cancer types in Western societies and predominately occurs in the elderly male. The strong age-related increase of prostate cancer is associated with a progressive accumulation of oxidative DNA damage which is presumably supported by a decline of the cellular antioxidative defence during ageing. Risk of developing prostate cancer is much lower in many Asian countries where soy-food is an integral part of diet. Therefore, isoflavones from soy were suggested to have chemopreventive activities in prostate cells. Here we have investigated the hypothesis that the soy-isoflavone genistein could protect DNA of LAPC-4 prostate cells from oxidative stress-related damage by enhancing the expression of antioxidative genes and proteins. A 24 h pre-incubation with genistein (1-30 µM) protected cells from hydrogen peroxide-induced DNA-damage, as determined by the comet assay. Analysis of two cDNA macro arrays, each containing 96 genes of biotransformation and stress response, revealed a modulated expression of three genes at 1 µM and of 19 genes at 10 µM genistein. Real time PCR confirmed the induction of three genes encoding products with antioxidant activities, namely glutathione reductase (2.7-fold), microsomal glutathione S-transferase 1 (1.9-fold) and metallothionein 1X (6.3-fold), at 1-30 µM genistein. 17
Received November 16, 2005
Revised March 27, 2006
Accepted May 19, 2006
CARCINOGENESIS
Genistein protects prostate cells against hydrogen peroxide-induced DNA damage and induces expression of genes involved in the defence against oxidative stress
Marian Raschke 1,
Ian R. Rowland 2,
Pamela J. Magee 2,
and
Beatrice L. Pool-Zobel 1 *
2 Northern Ireland Centre for Food and Health, University of Ulster, Coleraine, Northern Ireland BT52 1SA
Beatrice L. Pool-Zobel, E-mail: b8pobe{at}uni-jena.de
Abstract 
-estradiol, in contrast, decreased the expression of metallothionein 1X at 0.3 µM (2.0-fold), possibly pointing to an estrogen receptor-mediated regulation of this gene. Immunocytochemical staining revealed an induction of metallothionein proteins at 30 µM genistein, while their intracellular localisation was unaffected. Metallothioneins were previously found to protect cells from hydrogen peroxide-induced DNA damage. Hence, our findings indicate that genistein protects prostate cells from oxidative-stress related DNA damage presumably by inducing the expression of antioxidative products, such as metallothioneins. Genistein, therefore, might counteract the age related decline of important antioxidative defence systems which in turn maintain DNA integrity.
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