Nutrition Research and Practice

The Korean Nutrition Society (한국영양학회)
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Modulatory effects of $\alpha$- and $\gamma$-tocopherols on 4-hydroxyestradiol induced oxidative stresses in MCF-10A breast epithelial cells

  • Lee, Eun-Ju (Department of Food and Nutrition, Sookmyung Women's University) ;
  • Oh, Seung-Yeon (Department of Food and Nutrition, Sookmyung Women's University) ;
  • Kim, Mi-Kyung (National Cancer Center Institute) ;
  • Ahn, Sei-Hyun (Department of Surgery, College of Medicine and Asan Medical Center) ;
  • Son, Byung-Ho (Department of Surgery, College of Medicine and Asan Medical Center) ;
  • Sung, Mi-Kyung (Department of Food and Nutrition, Sookmyung Women's University)
  • Published : 2009.09.30
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Abstract

The elevated level of circulating estradiol increases the risk of breast tumor development. To gain further insight into mechanisms involved in their actions, we investigated the molecular mechanisms of 4-hydroxyestradiol (4-$OHE_2$) to initiate and/or promote abnormal cell growth, and of $\alpha$- or $\gamma$-tocopherol to inhibit this process. MCF-10A, human breast epithelial cells were incubated with $0.1{\mu}M$ 4-$OHE_2$, either with or without $30{\mu}M$ tocopherols for 96 h. 4-$OHE_2$ caused the accumulation of intracellular ROS, while cellular GSH/GSSG ratio and MnSOD protein levels were decreased, indicating that there was an oxidative burden. 4-$OHE_2$ treatment also changed the levels of DNA repair proteins, BRCA1 and PARP-1. $\gamma$-Tocopherol suppressed the 4-$OHE_2$-induced increases in ROS, GSH/GSSG ratio, and MnSOD protein expression, while $\alpha$-tocopherol up-regulated BRCA1 and PARP-1 protein expression. In conclusion, 4-$OHE_2$ increases oxidative stress reducing the level of proteins related to DNA repair. Tocopherols suppressed oxidative stress by scavenging ROS or up-regulating DNA repair elements.

Keywords

References

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