Modulatory effects of alpha- and gamma-tocopherols on 4-hydroxyestradiol induced oxidative stresses in MCF-10A breast epithelial cells
- Authors
- Lee, Eun-Ju; Oh, Seung-Yeon; Kim, Mi-Kyung; Ahn, Sei Hyun; Son, Byung Ho; Sung, Mi-Kyung
- Issue Date
- Sep-2009
- Publisher
- KOREAN NUTRITION SOC
- Keywords
- Breast cancer; DNA damage; 4-hydroxyestradiol; oxidative stress; tocopherol
- Citation
- NUTRITION RESEARCH AND PRACTICE, v.3, no.3, pp 185 - 191
- Pages
- 7
- Journal Title
- NUTRITION RESEARCH AND PRACTICE
- Volume
- 3
- Number
- 3
- Start Page
- 185
- End Page
- 191
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/13624
- DOI
- 10.4162/nrp.2009.3.3.185
- ISSN
- 1976-1457
2005-6168
- 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-OHE2) 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-OHE2, either with or without 30 mu M 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. gamma-Tocopherol suppressed the 4-OHE2-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-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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