» Articles » PMID: 15456407

Differential Induction of Quinone Reductase by Phytoestrogens and Protection Against Oestrogen-induced DNA Damage

Overview
Journal Biochem J
Specialty Biochemistry
Date 2004 Oct 1
PMID 15456407
Citations 14
Authors
Affiliations
Soon will be listed here.
Abstract

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 ERbeta (oestrogen receptor beta) 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 ERbeta transactivation at the electrophile response element of the QR gene promoter. By chromatin immunoprecipitation analysis, we show binding of ERalpha and ERbeta to the QR promoter, with increased ERbeta 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 ERbeta or QR. Our results with resveratrol are consistent with our hypothesis that the protective ability of resveratrol is partially dependent on the presence of ERbeta 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.

Citing Articles

The Role of Resveratrol in Cancer Therapy.

Ko J, Sethi G, Um J, Shanmugam M, Arfuso F, Kumar A Int J Mol Sci. 2017; 18(12).

PMID: 29194365 PMC: 5751192. DOI: 10.3390/ijms18122589.


Botanicals and Their Bioactive Phytochemicals for Women's Health.

Dietz B, Hajirahimkhan A, Dunlap T, Bolton J Pharmacol Rev. 2016; 68(4):1026-1073.

PMID: 27677719 PMC: 5050441. DOI: 10.1124/pr.115.010843.


Chemical and biological mechanisms of phytochemical activation of Nrf2 and importance in disease prevention.

Eggler A, Savinov S Recent Adv Phytochem. 2016; 43:121-155.

PMID: 26855455 PMC: 4739799. DOI: 10.1007/978-3-319-00581-2_7.


Modulation of Estrogen Chemical Carcinogenesis by Botanical Supplements used for Postmenopausal Women's Health.

Snelten C, Dietz B, Bolton J Drug Discov Today Dis Mech. 2013; 9(1).

PMID: 24223609 PMC: 3818722. DOI: 10.1016/j.ddmec.2012.11.001.


The aryl hydrocarbon receptor interacts with nuclear factor erythroid 2-related factor 2 to mediate induction of NAD(P)H:quinoneoxidoreductase 1 by 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Wang L, He X, Szklarz G, Bi Y, Rojanasakul Y, Ma Q Arch Biochem Biophys. 2013; 537(1):31-8.

PMID: 23800876 PMC: 4597779. DOI: 10.1016/j.abb.2013.06.001.


References
1.
Bhat H, Calaf G, Hei T, Loya T, Vadgama J . Critical role of oxidative stress in estrogen-induced carcinogenesis. Proc Natl Acad Sci U S A. 2003; 100(7):3913-8. PMC: 153022. DOI: 10.1073/pnas.0437929100. View

2.
Bianco N, Perry G, Smith M, Templeton D, Montano M . Functional implications of antiestrogen induction of quinone reductase: inhibition of estrogen-induced deoxyribonucleic acid damage. Mol Endocrinol. 2003; 17(7):1344-55. DOI: 10.1210/me.2002-0382. View

3.
Yang S, Kim J, Oh T, Kim M, Lee S, Woo S . Genome-scale analysis of resveratrol-induced gene expression profile in human ovarian cancer cells using a cDNA microarray. Int J Oncol. 2003; 22(4):741-50. View

4.
Seike N, Wanibuchi H, Morimura K, Wei M, Nishikawa T, Hirata K . Enhancement of lung carcinogenesis by nonylphenol and genistein in a F344 rat multiorgan carcinogenesis model. Cancer Lett. 2003; 192(1):25-36. DOI: 10.1016/s0304-3835(02)00684-5. View

5.
Magee P, Rowland I . Phyto-oestrogens, their mechanism of action: current evidence for a role in breast and prostate cancer. Br J Nutr. 2004; 91(4):513-31. DOI: 10.1079/BJN20031075. View