Advisor(s)
Trygve Tollefsbol
Committee Member(s)
Vithal Ghanta
Chandrika Piyathilake
Document Type
Thesis
Date of Award
2011
Abstract
In breast cancer treatment, the presence of the estrogen receptor-alpha (ERα) plays an important role with hormonal-responsive drugs such as tamoxifen. ERα-negative breast cancers are more aggressive not only because of the increased uncontrollable growth but also because of the lack of target-directed treatments. Bioactive dietary components such as green tea polyphenols (GTPs) and sulforaphane (SFN, found in cruciferous vegetables) have been shown to have anti-cancer properties. In this study, we found that the dietary combination of a DNA methyltransferases (DNMTs) inhibitor, GTPs, and a histone deacetylase (HDAC) inhibitor, SFN, dose-dependently inhibited the proliferation of ERα-negative MDA-MB-231 human breast cancer cells. Combination GTPs and SFN treatment also epigenetically reactivated ERα expression in ERα-negative MDA-MB-231 breast cancer cells both at the gene and protein level. A combination of GTPs and SFN significantly inhibited DNMTs and HDAC activity, which is consistently associated with ERα promoter hypomethylation and hyperacetylation, respectively. In addition, a global decrease in methylation was also observed with combination GTPs and SFN treatment. Furthermore, treatment with tamoxifen in combination with GTPs and SFN significantly inhibited ERα-negative MDA-MB-231 breast cancer cellular proliferation and increased apoptosis of the cells. Collectively, this investigation provides a novel combination therapy of GTPs and SFN on hormonal refractory breast cancer with available drugs such as tamoxifen.
ProQuest Publication Number
ISBN
978-1-124-89111-8
Recommended Citation
Patel, Shweta Naran, "Reactivation of estrogen receptor-α (ERα) by bioactive dietary compounds through epigenetic mechanisms in ERα-negative breast cancer cells" (2011). All ETDs from UAB. 2675.
https://digitalcommons.library.uab.edu/etd-collection/2675
Comments
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