title: Natural antioxidants exhibit chemopreventive characteristics through the regulation of CNC b-Zip transcription factors in estrogen-induced breast carcinogenesis.
abstract: The objective of the present study was to characterize the role of resveratrol (Res) and vitamin C (VC) in prevention of estrogen-induced breast cancer through regulation of cap "n"collar (CNC) b-zip transcription factors. Human breast epithelial cell line MCF-10A was treated with 17β-estradiol (E2) and VC or Res with or without E2. mRNA and protein expression levels of CNC b-zip transcription factors nuclear factor erythroid 2-related factor 1 (Nrf1), nuclear factor erythroid 2 related factor 2 (Nrf2), nuclear factor erythroid 2 related factor 3 (Nrf3), and Nrf2-regulated antioxidant enzymes superoxide dismutase 3 (SOD3) and
  quinone oxidoreductase 1 (NQO1) were quantified. The treatment with E2 suppressed, whereas VC and Res prevented E2-mediated decrease in the expression levels of SOD3, NQO1, Nrf2 mRNA, and protein in MCF-10A cells. The treatment with E2, Res, or VC significantly increased mRNA and protein expression levels of Nrf1. 17β-Estradiol treatment significantly increased but VC or Res decreased Nrf3 mRNA and protein expression levels. Our studies demonstrate that estrogen-induced breast cancer might be prevented through upregulation of antioxidant enzymes via Nrf-dependent pathways.
authors.affiliation: Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO, 64108, USA. bhath@umkc.edu.
authors.forename: Anwesha
authors.initials: A
authors.lastname: Chatterjee
authors.forename: Amruta
authors.initials: A
authors.lastname: Ronghe
authors.forename: Bhupendra
authors.initials: B
authors.lastname: Singh
authors.forename: Nimee K
authors.initials: NK
authors.lastname: Bhat
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Hari K
authors.initials: HK
authors.lastname: Bhat
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism*; D001943:Breast Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control; D045744:Cell Line, Tumor; D004958:Estradiol / Q000009:adverse effects* / Q000494:pharmacology; D004967:Estrogens / Q000009:adverse effects* / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis*; D009363:Neoplasm Proteins / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000096:biosynthesis*
chemical_list: D000975:Antioxidants; D050976:Basic-Leucine Zipper Transcription Factors; D004967:Estrogens; D009363:Neoplasm Proteins; D004958:Estradiol; C441642:SOD3 protein, human; D013482:Superoxide Dismutase; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human
keywords: Breast Cancer; CNC b-zip Transcription Factors; Estrogen; Resveratrol; Vitamin C