Lack of significant genotoxicity of purified soy isoflavones (genistein, daidzein, and glycitein) in 20 patients with prostate cancer

Miltyk, Woytek; Craciunescu, Corneliu N.; Fischer, Leslie M.; Jeffcoat, R; Koch, Matthew; Lopaczynski, Wlodek; Mahoney, Chrysa; Crowell, James A.; Paglieri, Jennifer; Zeisel, Steven H.

doi:10.1093/ajcn/77.4.875

Cited by 102 publications

(67 citation statements)

References 44 publications

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“…The required concentrations for genotoxicity described in these studies ranged from 5 to 25 lM. However, when mice or humans are exposed to higher levels of dietary isoflavones, genetic damage is not observed (Record et al 1995;Miltyk et al 2003).…”

Section: Discussionmentioning

confidence: 91%

Chemoprotective activity of the isoflavones, genistein and daidzein on mutagenicity induced by direct and indirect mutagens in cultured HTC cells

et al. 2012

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Isoflavones are phenolic compounds widely distributed in plants and found in a high percentage in soybeans. They have important biological properties and are regarded as potential chemopreventive agents. The aim of this study was to verify the preventive effect of two soy isoflavones (genistein and daidzein) by a micronucleus assay, analysis of GST activity, and real-time RT-PCR analysis of GSTa2 gene expression. Mutagens of direct (doxorubicin) and indirect (2-aminoanthracene) DNA damage were used. Hepatoma cells (HTC) were treated with genistein or daidzein for 26 h at noncytotoxic concentrations; 10 lM when alone, and 0.1, 1.0 and 10 lM when combined with genotoxic agents. The micronucleus test demonstrated that both isoflavones alone had no genotoxic effect. Genistein showed antimutagenic effects at 10 lM with both direct and indirect DNA damage agents. On phase II enzyme regulation, the current study indicated an increase in total cytoplasmic GST activity in response to genistein and daidzein at 10 lM supplementation. However, the mRNA levels of GSTa2 isozymes were not differentially modulated by genistein or daidzein. The results point to an in vitro antimutagenic activity of genistein against direct and indirect DNA damage-induced mutagenicity.

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Section: Discussionmentioning

confidence: 91%

Chemoprotective activity of the isoflavones, genistein and daidzein on mutagenicity induced by direct and indirect mutagens in cultured HTC cells

et al. 2012

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“…In human feeding studies, consumption of high-soy diets for 10 weeks yielded plasma levels of genistein of 700 nM with large interindividual variation [Wiseman et al, 2004]. Dietary supplementation with a purified genistein-daidzein-glycitein ''bullet'' that delivers genistein amounts 3-to 4-fold greater than a soy-rich Japanese diets yielded plasma genistein levels in humans up to 27 lM, with minimal reported DNA toxicity [Bloedon et al, 2002;Miltyk et al, 2003]. In our recent review of the potential genotoxic effects of genistein we note that DNA damaging and other potentially adverse effects were primarily induced by high genistein concentrations in the 25-200 lM dose range, therefore we have used a low 3.125 lM concentration of genistein that we show here to be nontoxic to MCF-7 and MDA-MB-468 breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Modulation of gene methylation by genistein or lycopene in breast cancer cells

King-Batoon

Leszczyńska

Klein

2008

Environ and Mol Mutagen

207

113

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Dietary agents with chemopreventive potential, including soy-derived genistein and tomato-derived lycopene, have been shown to alter gene expression in ways that can either promote or potentially inhibit the carcinogenic processes. To begin to explore the mechanisms by which these agents may be acting we have examined the DNA methylation modulating capacity of genistein or lycopene for several genes relevant to breast cancer in the breast cancer cell lines MCF-7 and MDA-MB-468, as well as in immortalized but noncancer fibrocystic MCF10A breast cells. We find using methylation specific PCR (MSP) that a low, nontoxic concentration of genistein (3.125 lM, resupplemented every 48 hr for 1 week) or a single dose of lycopene (2 lM) partially demethylates the promoter of the GSTP1 tumor suppressor gene in MDA-MB-468 cells. RT-PCR studies confirm a lack of GSTP1 expression in untreated MDA-MB-468, with restoration of GSTP1 expression after genistein or lycopene treatment. The RARb2 gene however, was not demethylated by genistein or lycopene in either of these breast cancer cell lines. But, lycopene (2 lM, once per week for 2 weeks) did induce demethylation of RARb2 and the HIN-1 genes in the noncancer MCF10A fibrocystic breast cells. These data show for the first time that the tomato carotenoid lycopene has direct DNA demethylating activity. In summary, both genistein and lycopene, at very low, dietarily relevant concentrations can potentially mitigate tumorigenic processes via promoter methylation modulation of gene expression. Environ. Mol. Mutagen. 49:36-45, 2008.

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“…Oral administration of soy isoflavones gives plasma concentrations of genistein up to 16.3 μM that have been associated with antimetastatic activity in vitro [10]. No genotoxicity has been found in subjects treated with a purified soy unconjugated isoflavone mixture [143].…”

Section: Clinical Trials: Effects On Patients With Prostate Cancermentioning

confidence: 99%

Multi-targeted therapy of cancer by genistein

Banerjee¹,

Li²,

Wang³

et al. 2008

Cancer Letters

550

383

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Soy isoflavones have been identified as dietary components having an important role in reducing the incidence of breast and prostate cancers in Asian countries. Genistein, the predominant isoflavone found in soy products, has been shown to inhibit the carcinogenesis in animal models. There is a growing body of experimental evidence showing that the inhibition of human cancer cell growth by genisteinis mediated via the modulation of genes that are related to the control of cell cycle and apoptosis. It has been shown that genistein inhibits the activation of NF-κB and Akt signaling pathways, both of which are known to maintain a homeostatic balance between cell survival and apoptosis. Moreover, genistein antagonizes estrogen-and androgen-mediated signaling pathways in the processes of carcinogenesis. Furthermore, genistein has been found to have antioxidant properties, and shown to be a potent inhibitor of angiogenesis and metastasis. Taken together, both in vivo and in vitro studies have clearly shown that genistein, one of the major soy isoflavones, is a promising agent for cancer chemoprevention and further suggest that it could be an adjunct to cancer therapy by virtue of its effects on reversing radioresistance and chemoresistance. In this review, we attempt to provide evidence for these preventive and therapeutic effects of genistein in a succinct manner highlighting comprehensive state-of-the-art knowledge regarding its multi-targeted biological and molecular effects in cancer cells.

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Lack of significant genotoxicity of purified soy isoflavones (genistein, daidzein, and glycitein) in 20 patients with prostate cancer

Abstract: Although isoflavones are capable of inducing genetic damage in vitro, a similar effect was not observed in subjects treated with a purified soy unconjugated isoflavone mixture.

Cited by 102 publications

References 44 publications

Chemoprotective activity of the isoflavones, genistein and daidzein on mutagenicity induced by direct and indirect mutagens in cultured HTC cells

Chemoprotective activity of the isoflavones, genistein and daidzein on mutagenicity induced by direct and indirect mutagens in cultured HTC cells

Modulation of gene methylation by genistein or lycopene in breast cancer cells

Multi-targeted therapy of cancer by genistein

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