Modulatory effects of alpha- and gamma-tocopherols on 4-hydroxyestradiol induced oxidative stresses in MCF-10A breast epithelial cells.
- Author:
Eun Ju LEE
1
;
Seung Yeon OH
;
Mi Kyung KIM
;
Sei Hyun AHN
;
Byung Ho SON
;
Mi Kyung SUNG
Author Information
- Publication Type:Original Article
- Keywords: Breast cancer; DNA damage; 4-hydroxyestradiol; oxidative stress; tocopherol
- MeSH: alpha-Tocopherol; Breast; Breast Neoplasms; DNA Damage; DNA Repair; Epithelial Cells; Estradiol; Estrogens, Catechol; gamma-Tocopherol; Humans; Oxidative Stress; Proteins; Tocopherols
- From:Nutrition Research and Practice 2009;3(3):185-191
- CountryRepublic of Korea
- Language:English
- 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 microM 4-OHE2, either with or without 30 microM 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.
