All ETDs from UAB

Advisory Committee Chair

Trygve Tollefsbol

Advisory Committee Members

Vithal Ghanta

Chandrika Piyathilake

Document Type

Thesis

Date of Award

2011

Degree Name by School

Master of Science (MS) College of Arts and Sciences

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.

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