부산대학교 도서관

Breast cancer is the most common cancer and the leading cause of cancer death in women. Although tamoxifen therapy is successful for some patients, it does not provide adequate benefit for those who have estrogen receptor (ER)-negative cancers. Therefore, we approached novel treatment strategies by combining two potential bioactive dietary supplements for the reactivation of ERa expression for effective treatment of ERα-negative breast cancer with tamoxifen. Bioactive dietary supplements such as green tea polyphenols (GTPs) and sulforaphane (SFN) inhibit DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), respectively, which are of central importance to cancer prevention. In the present study, we have observed that treatment of ERa-negative breast cancer cells with GTPs and SFN alone or in combination leads to the reactivation of ERa expression. The combination of 20 mg/mL GTPs and 5 μM SFN was found to be the optimal dose of ERareactivation at 3 days in MDA-MB-231 cells. The reactivation of ERa expression was consistently correlated with ERa promoter hypomethylation and hyperacetylation. Chromatin immunoprecipitation (ChIP) analysis of the ERa promoter revealed that GTPs and SFN altered the binding of ERα-transcriptional co-repressor complex thereby contributing to ERareactivation. In addition, treatment with tamoxifen in combination with GTPs and SFN significantly increased both cell death and inhibition of cellular proliferation in MDA-MB-231 cells in comparison to treatment with tamoxifen alone. Collectively, our findings suggest that a novel combination of bioactive-HDAC inhibitors with bioactive-demethylating agents is a promising strategy for the effective treatment of hormonal refractory breast cancer with available anti-estrogens. [ABSTRACT FROM AUTHOR]