Resveratrol suppresses 4-hydroxyestradiol-induced transformation of human breast epithelial cells by blocking IκB kinaseβ-NF-κB signalling

Free Radical Research
Sin-Aye ParkYoung-Joon Surh

Abstract

Excess estrogen stimulates the proliferation of mammary epithelial cells and hence represents a major risk factor for breast cancer. Estrogen is subjected to cytochrome P450-catalysed oxidative metabolism to produce an oncogenic catechol estrogen, 4-hydroxyestradiol (4-OHE₂). 4-OHE₂ undergoes redox cycling during which reactive oxygen species (ROS) as well as the chemically reactive estrogen semiquinone and quinone intermediates are produced, thereby contributing to hormonal carcinogenesis. Resveratrol (3,4',5-trihydroxy stilbene), a phytoalexin present in grapes, has been reported to possess chemopreventive and chemotherapeutic activities. In the present study, we examined the inhibitory effects of resveratrol on 4-OHE₂-induced transformation of human breast epithelial MCF-10A cells. Resveratrol inhibited migration and anchorage-independent growth of MCF-10A cells treated with 4-OHE₂. Resveratrol treatment suppressed the 4-OHE₂-induced activation of IκB kinaseβ (IKKβ) and phosphorylation of IκBα, and consequently NF-κB DNA binding activity and cyclooxygenase-2 (COX-2) expression. Resveratrol suppressed ROS production and phosphorylation of Akt and ERK induced by 4-OHE₂ treatment. In conclusion, resveratrol blocks activation of...Continue Reading

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Citations

May 9, 2015·Seminars in Cancer Biology·Abbas K SamadiXujuan Yang
Feb 9, 2016·Seminars in Cancer Biology·Nagendra Sastry YarlaGovinda Rao Duddukuri
Apr 3, 2016·Cancer Letters·Sahdeo PrasadAmit K Tyagi
Jun 21, 2012·Free Radical Research·Hideyuki J Majima, Shinya Toyokuni
Jan 6, 2021·Oncotarget·Randa El-ZeinSherif Z Abdel-Rahman
Sep 1, 2021·Pharmacological Reports : PR·Beata Starek-ŚwiechowiczAndrzej Starek

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