Prevention of estrogen-DNA adduct formation in MCF-10F cells by resveratrol

Muhammad Zahid, Nilesh W. Gaikwad, Mohamed F. Ali, Fang Lu, Muhammad Saeed, Li Yang, Eleanor G. Rogan, Ercole L. Cavalieri

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Resveratrol (Resv), a natural occurring phytolexin present in grapes and other foods, possesses chemopreventive effects revealed by its striking modulation of diverse cellular events associated with tumor initiation, promotion, and progression. Catechol estrogens generated in the metabolism of estrogens are oxidized to catechol quinones that react with DNA to form predominantly depurinating estrogen-DNA adducts. This event can generate the mutations responsible for cancer initiation. In this regard, Resv acts as both an antioxidant and an inducer of the phase II enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1). In this report, we present the effects of Resv on the metabolism of estrogens in normal breast epithelial cells (MCF-10F) treated with 4-hydroxyestradiol (4-OHE2) or estradiol-3,4-quinone (E2-3,4-Q). Resv induced NQO1 in a dose- and time-dependent manner, but did not affect the expression of catechol-O-methyltransferase. Ultraperformance liquid chromatography/tandem mass spectrometry was used to determine the effects of Resv on estrogen metabolism. Preincubation of the cells with Resv for 48 h decreased the formation of depurinating estrogen-DNA adducts from 4-OHE2 or E2-3,4-Q and increased formation of methoxycatechol estrogens. When Resv was also present with the 4-OHE2 or E2-3,4-Q, even greater increases in methoxycatechol estrogens were observed, and the DNA adducts were undetectable. We conclude that Resv can protect breast cells from carcinogenic estrogen metabolites, suggesting that it could be used in breast cancer prevention.

Original languageEnglish (US)
Pages (from-to)136-145
Number of pages10
JournalFree Radical Biology and Medicine
Volume45
Issue number2
DOIs
StatePublished - Jul 15 2008
Externally publishedYes

Keywords

  • Catechol estrogen quinones
  • Catechol estrogens
  • Depurinating estrogen-DNA adducts
  • Methoxycatechol estrogens
  • Quinone reductase
  • Resveratrol

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

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  • Cite this

    Zahid, M., Gaikwad, N. W., Ali, M. F., Lu, F., Saeed, M., Yang, L., Rogan, E. G., & Cavalieri, E. L. (2008). Prevention of estrogen-DNA adduct formation in MCF-10F cells by resveratrol. Free Radical Biology and Medicine, 45(2), 136-145. https://doi.org/10.1016/j.freeradbiomed.2008.03.017