Modulatory effects of α- and γ-tocopherols on 4-hydroxyestradiol induced oxidative stresses in MCF-10A breast epithelial cells

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 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.

Vitamin E and carotenoid accumulation during kernel development in two varieties of Castanea henryi

“…For WS, γ‐tocopherol increased from 14.60 μg g −1 FW at S1 to 27.03 μg g −1 FW at S2 and then increased slightly, and a steady rise was discovered in YS during the whole development periods. Health benefits of γ‐tocopherol were generally reported as antioxidants, and a previous study has found that γ‐tocopherol was able to reduce the oxidative burden by inhibiting the accumulation of reactive oxygen species induced by 4‐hydroxyestradiol, leading to the decrease risk of breast tumours (Lee et al ., 2009). In addition, γ‐tocopherol and its physiological metabolite showed anti‐inflammatory properties in vivo , of which α‐tocopherol contributed less (Jiang & Ames, 2003).…”

Iron, Oxidative Stress, and Cancer

“…47 In our previous study, the expression of DNA repair protein was suppressed by 4-OHE in MCF-10A breast epithelial cells. 48 Excess iron may replace zinc in zinc finger of estrogen receptor producing more free radicals. Alcohol, a well-known risk factor of breast cancer triggers the release of iron ion from ferritin, which may explain a part of the mechanisms of action.…”

Cytoprotective effect of γ-tocopherol against tumor necrosis factor α induced cell dysfunction in L929 cells

“…Multiple studies have demonstrated the potent anti-oxidant effects of γ-tocopherol, the minor component of the antioxidant vitamin E. As opposed to α-tocopherol (which is the principal component of Vitamin E), γ-tocopherol exerts protective effects against both reactive oxygen and reactive nitrogen species in various cell types, resulting in potent cytoprotective effects in various experimental systems (1-3). …”