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Effect of α‐ and γ‐Tocopherols on 4‐Hydroxyestradiol Induced Oxidative Stresses in MCF‐10A Breast Epithelial Cells
Author(s) -
Sung MiKyung,
Lee EunJu,
Oh SeungYeon
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.315.4
Subject(s) - oxidative stress , dna damage , glutathione , dna repair , intracellular , oxidative phosphorylation , chemistry , poly adp ribose polymerase , mcf 7 , reactive oxygen species , microbiology and biotechnology , cancer research , biochemistry , biology , dna , breast cancer , cancer , human breast , enzyme , genetics , polymerase
Both estrogen and oxidative stress are known risk factors for breast cancer development. Human breast epithelial cells(MCF‐10A) were incubated with 0.1uM 4‐ Hydroxyestradiol (4‐OHE 2 )with or without 30uM α‐, γ‐tocopherols(α‐T, γ‐T) for 24 to 96hrs. Intracellular ROS, glutathione and MnSOD expression as oxidative stress markers were measured. The level of DNA damage repair‐related protein including p53, PARP‐1, and BRCA1 were also measured. By oxidative stimuli, p53 is phophorylated and PARP‐1 was cleavaged, which leads to DNA repair. PARP‐1 is also essential in regulating BRCA1 in response to DNA damage. Results showed 4‐ OHE 2 increased the intracellular ROS level with a down‐regulation of MnSOD protein. A significant negative correlation was found between ROS level and GSH/GSSG ratio. Cleavaged PARP‐1 was increased and BRCA1 and PARP‐1 depletion was observed with ROS accumulation. γ‐T reduced 4‐OHE 2 ‐induced ROS, while increased GSH/GSSG ratio and MnSOD protein. γ‐T also up‐regulated phosphorylated p53 protein. α‐T is shown to up‐regulate BRCA 1 and PARP‐1 protein. In conclusion, 4‐OHE 2 increases oxidative stresses which possibly down‐regulate protein related to DNA repair. α‐and γ‐T may prevent 4‐OHE 2 induced oxidative stress and DNA damage and thereby retard breast tumor development. This work was supported by the Korea Research Foundation Grant(KRF‐2005‐042‐C00194).