Quinone reductase (QR) is a phase II detoxification enzyme that plays an important role in detoxifying quinones and may help maintain the antioxidant function of the cell. We have previously observed that QR is up-regulated by anti-oestrogens, but not oestrogen, in breast cancer cells via ERβ (oestrogen receptor β) transactivation. Such QR induction appears to protect breast cells against oestrogen-induced oxidative DNA damage, most likely by reducing reactive oestrogen metabolites termed catecholestrogen-quinones back to the hydroxy-catecholestrogens which may be conjugated. We now report that the phytoestrogens biochanin A, genistein and resveratrol also up-regulate QR expression in breast cancer cells. We observe that regulation can occur at the transcriptional level, preferentially through ERβ transactivation at the electrophile response element of the QR gene promoter. By chromatin immunoprecipitation analysis, we show binding of ERα and ERβ to the QR promoter, with increased ERβ binding in the presence of resveratrol. Functional studies show that biochanin A and resveratrol, but not genistein, can significantly protect against oestrogen-induced oxidative DNA damage in breast cancer cells. Antisense technology was used to determine whether such protection was dependent on ERβ or QR. Our results with resveratrol are consistent with our hypothesis that the protective ability of resveratrol is partially dependent on the presence of ERβ and QR. In conclusion, we postulate that phytoestrogen-mediated induction of QR may represent an additional mechanism for breast cancer protection, although the effects may be specific for a given phytoestrogen.
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Research Article|
December 14 2004
Differential induction of quinone reductase by phytoestrogens and protection against oestrogen-induced DNA damage
Nicole R. BIANCO;
Nicole R. BIANCO
1Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106, U.S.A.
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Laura J. CHAPLIN;
Laura J. CHAPLIN
1Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106, U.S.A.
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Monica M. MONTANO
Monica M. MONTANO
1
1Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106, U.S.A.
1To whom correspondence should be addressed (email mxm126@po.cwru.edu).
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Publisher: Portland Press Ltd
Received:
June 07 2004
Revision Received:
August 16 2004
Accepted:
September 30 2004
Accepted Manuscript online:
September 30 2004
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2005
Biochem J (2005) 385 (1): 279–287.
Article history
Received:
June 07 2004
Revision Received:
August 16 2004
Accepted:
September 30 2004
Accepted Manuscript online:
September 30 2004
Citation
Nicole R. BIANCO, Laura J. CHAPLIN, Monica M. MONTANO; Differential induction of quinone reductase by phytoestrogens and protection against oestrogen-induced DNA damage. Biochem J 1 January 2005; 385 (1): 279–287. doi: https://doi.org/10.1042/BJ20040959
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