Resveratrol and N-acetylcysteine block the cancer-initiating step in MCF-10F cells

Muhammad Zahid, Muhammad Saeed, Cheryl Beseler, Eleanor G Rogan, Ercole Cavalieri

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Substantial evidence suggests that catechol estrogen-3,4-quinones react with DNA to form predominantly the depurinating adducts 4-hydroxyestrone (estradiol)-1-N3Ade [4-OHE1(E2)-1-N3Ade] and 4-OHE 1(E2)-1-N7Gua. Apurinic sites resulting from these adducts generate critical mutations that can initiate cancer. The paradigm of cancer initiation is based on an imbalance in estrogen metabolism between activating pathways that lead to estrogen-DNA adducts and deactivating pathways that lead to estrogen metabolites and conjugates. This imbalance can be improved to minimize formation of adducts by using antioxidants, such as resveratrol (Resv) and N-acetylcysteine (NAcCys). To compare the ability of Resv and NAcCys to block formation of estrogen-DNA adducts, we used the human breast epithelial cell line MCF-10F treated with 4-OHE2. Resv and NAcCys directed the metabolism of 4-OHE2 toward protective pathways. NAcCys reacted with the quinones and reduced the semiquinones to catechols. This pathway was also carried out by Resv. In addition, Resv induced the protective enzyme quinone reductase, which reduces E1(E2)-3,4-quinones to 4-OHE 1(E2). Resv was more effective at increasing the amount of 4-OCH3E1(E2) than NAcCys. Inhibition of estrogen-DNA adduct formation was similar at lower doses, but at higher doses Resv was about 50% more effective than NAcCys. Their combined effects were additive. Therefore, these two antioxidants provide an excellent combination to protect catechol estrogens from oxidation to catechol quinones.

Original languageEnglish (US)
Pages (from-to)78-85
Number of pages8
JournalFree Radical Biology and Medicine
Volume50
Issue number1
DOIs
StatePublished - Jan 1 2011

Fingerprint

Acetylcysteine
Estrogens
Quinones
DNA Adducts
Neoplasms
Metabolism
Antioxidants
Catechol Estrogens
Catechols
NAD(P)H Dehydrogenase (Quinone)
Metabolites
resveratrol
Estradiol
Breast
Epithelial Cells
Cell Line
Oxidation
Mutation
DNA
Enzymes

Keywords

  • Balanced estrogen metabolism
  • Cancer prevention
  • Catechol estrogen quinones
  • Depurinating estrogen-DNA adducts
  • Free radicals

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Resveratrol and N-acetylcysteine block the cancer-initiating step in MCF-10F cells. / Zahid, Muhammad; Saeed, Muhammad; Beseler, Cheryl; Rogan, Eleanor G; Cavalieri, Ercole.

In: Free Radical Biology and Medicine, Vol. 50, No. 1, 01.01.2011, p. 78-85.

Research output: Contribution to journalArticle

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