Cellular DNA breakage by soy isoflavone genistein and its methylated structural analogue biochanin A

Ullah, Mohammad Fahad; Shamim, Uzma; Hanif, Sarmad; Azmi, Asfar S.; Hadi, S. M.

doi:10.1002/mnfr.200800547

Cited by 46 publications

(35 citation statements)

References 59 publications

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“…This is in accord with reports in the literature showing the protective effect of genistein on free radical-induced oxidative damage in MC3T3-E1 osteoblast-like cells and the protection of H2O2-induced human lymphocytes DNA damage (18)(19)(20). The results from proliferation assays mirrored the effects on apoptosis, with genistein protecting against the reduction in proliferation from HG-induced oxidative stress.…”

Section: Discussionsupporting

confidence: 91%

Mechanisms of Genistein Protection on Pancreas Cell Damage in High Glucose Condition

Zhong

Liu

2011

Intern. Med.

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Aim An adequate β cell number is important to prevent the onset and development of type 2 diabetes. The aim of this study was to determine if phytoestrogen gesintein has protective effects against high glucoseinduced cell apoptosis in human pancreas cells, and to try to determine the possible mechanism for this protection. Methods Human pancreatic β cells were subjected to normal (5 mM) or high glucose (25 mM) with and without the presence of 100nM genistein, and also in the presence and absence of the pure anti-estrogen ICI-182780 (100 nM). Bcl-2 siRNA transfection was performed to investigate if the effect of genistein was also Bcl-2 dependent. Cell proliferation and apoptosis were determined by Tritiated Thymidine Incorporation Assay and Cell Apoptosis Detection ELISA. Estrogen receptor and Bcl-2 mRNA expression was measured by Real-time Quantitative PCR. Results High glucose concentration caused cell proliferation inhibition and apoptosis in cultured human pancreatic β cells, and these effects were significantly reversed by genistein (P<0.01). Estrogen receptor beta was expressed in the cultured cells, and genistein protection was blocked by ICI-182780 administration as well as Bcl-2 siRNA transfection. Conclusion Phytoestrogen gave protection against high glucose-induced pancreatic cell damage through estrogen receptor beta and Bcl-2 dependent pathways.

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Section: Discussionsupporting

confidence: 91%

Mechanisms of Genistein Protection on Pancreas Cell Damage in High Glucose Condition

Zhong

Liu

2011

Intern. Med.

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“…All the three ROS scavengers caused significant inhibition of DNA breakage as evidenced by decreased tail lengths of comets in both the control as well as copper-administered group. In earlier reports (Ullah et al 2009;Azmi et al 2006), we have proposed that polyphenol induced cellular DNA degradation is the result of the formation of ROS such as the hydroxyl radicals. Further, due to the site specific nature of the reaction of hydroxyl radicals with DNA, it is difficult for any trapping molecule to intercept them completely (Czene et al 1997).…”

Section: Resultsmentioning

confidence: 98%

“…2b. In previous publications we have established the mobilization of endogenous copper ions by using various metal ion chelators (Shamim et al 2008;Ullah et al 2009). The results given in Fig.…”

Section: Resultsmentioning

confidence: 99%

Oral administration of copper to rats leads to increased lymphocyte cellular DNA degradation by dietary polyphenols: implications for a cancer preventive mechanism

et al. 2011

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To account for the observed anticancer properties of plant polyphenols, we have earlier proposed a mechanism which involves the mobilization of endogenous copper ions by polyphenols leading to the generation of reactive oxygen species (ROS) that serve as proximal DNA cleaving agents and lead to cell death. Over the last decade we have proceeded to validate our hypothesis with considerable success. As a further confirmation of our hypothesis, in this paper we first show that oral administration of copper to rats leads to elevated copper levels in lymphocytes. When such lymphocytes with a copper overload were isolated and treated with polyphenols EGCG, genistein and resveratrol, an increased level of DNA breakage was observed. Further, preincubation of lymphocytes having elevated copper levels with the membrane permeable copper chelator neocuproine, resulted in inhibition of polyphenol induced DNA degradation. However, membrane impermeable chelator of copper bathocuproine, as well as iron and zinc chelators were ineffective in causing such inhibition in DNA breakage, confirming the involvement of endogenous copper in polyphenol induced cellular DNA degradation. It is well established that serum and tissue concentrations of copper are greatly increased in various malignancies. In view of this fact, the present results further confirm our earlier findings and strengthen our hypothesis that an important anticancer mechanism of plant polyphenols could be the mobilization of intracellular copper leading to ROS-mediated cellular DNA breakage. In this context, it may be noted that cancer cells are under considerable oxidative stress and increasing such stress to cytotoxic levels could be a successful anticancer approach.

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“…In addition to their antioxidant activity, anticancer agents have also been proposed to possess pro-oxidant activity, particularly in the presence of the transition metal copper. With the reported increased levels of copper in cancer tissues, the pro-oxidant activity leads to effective killing of cancer cells (44)(45)(46). Isoflavones genistein and biochanin A have been shown to mobilize nuclear copper in human lymphocytes, resulting in the degradation of cellular DNA.…”

Section: Oxidative Damagementioning

confidence: 99%

“…Isoflavones genistein and biochanin A have been shown to mobilize nuclear copper in human lymphocytes, resulting in the degradation of cellular DNA. These compounds also served as antioxidants against tert-butylhydroperoxide-induced oxidative breakage (45).…”

Section: Oxidative Damagementioning

confidence: 99%

Perspectives on the Role of Isoflavones in Prostate Cancer

Ahmad

Biersack

et al. 2013

AAPS J

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Abstract. Isoflavones have been investigated in detail for their role in the prevention and therapy of prostate cancer. This is primarily because of the overwhelming data connecting high dietary isoflavone intake with reduced risk of developing prostate cancer. A number of investigations have evaluated the mechanism(s) of anticancer action of isoflavones such as genistein, daidzein, biochanin A, equol, etc., in various prostate cancer models, both in vitro and in vivo. Genistein quickly jumped to the forefront of isoflavone cancer research, but the initial enthusiasm was followed by reports on its contradictory prometastatic and tumor-promoting effects. Use of soy isoflavone mixture has been advocated as an alternative, wherein daidzein can negate harmful effects of genistein. Recent research indicates a novel role of genistein and other isoflavones in the potentiation of radiation therapy, epigenetic regulation of key tumor suppressors and oncogenes, and the modulation of miRNAs, epithelial-to-mesenchymal transition, and cancer stem cells, which has renewed the interest of cancer researchers in this class of anticancer compounds. This comprehensive review article summarizes our current understanding of the role of isoflavones in prostate cancer research.

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Cellular DNA breakage by soy isoflavone genistein and its methylated structural analogue biochanin A

Cited by 46 publications

References 59 publications

Mechanisms of Genistein Protection on Pancreas Cell Damage in High Glucose Condition

Mechanisms of Genistein Protection on Pancreas Cell Damage in High Glucose Condition

Oral administration of copper to rats leads to increased lymphocyte cellular DNA degradation by dietary polyphenols: implications for a cancer preventive mechanism

Perspectives on the Role of Isoflavones in Prostate Cancer

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