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Natural Antioxidants Exhibit Chemopreventive Characteristics through the Regulation of CNC b‐Zip Transcription Factors in Estrogen‐Induced Breast Carcinogenesis

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 NAD(P)H: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.