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KMID : 1239920090030030185
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Nutrition Research and Practice
2009 Volume.3 No. 3 p.185 ~ p.191
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Modulatory effects of α- and γ-tocopherols on 4-hydroxyestradiol induced oxidative stresses in MCF-10A breast epithelial cells
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Lee Eun-Ju
Oh Seung-Yeon
Kim Mi-Kyung
Ahn Sei-Hyun
Son Byung-Ho
Sung Mi-Kyung
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Abstract
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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-OHE2) to initiate and/or promote abnormal cell growth, and of α- or γ-tocopherol to inhibit this process. MCF-10A, human breast epithelial cells were incubated with 0.1 μM 4-OHE2, either with or without 30 μM tocopherols for 96 h. 4-OHE2 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-OHE2 treatment also changed the levels of DNA repair proteins, BRCA1 and PARP-1. γ-Tocopherol suppressed the 4-OHE2-induced increases in ROS, GSH/GSSG ratio, and MnSOD protein expression, while α-tocopherol up-regulated BRCA1 and PARP-1 protein expression. In conclusion, 4-OHE2 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.
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KEYWORD
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Breast cancer, DNA damage, 4-hydroxyestradiol, oxidative stress, tocopherol
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