Epigenetic reactivation of p21(CIP1/WAF1) and KLOTHO by a combination of bioactive dietary supplements is partially ER alpha-dependent in ER alpha-negative human breast cancer cells

摘要

Available treatment strategies against estrogen receptor (ER)-negative breast cancer patients are limited due to their poor response to hormonal therapy. We have shown previously that the combinations of green tea polyphenols (GTPs), a dietary DNA methyltransferase inhibitor, and sulforaphane (SFN), a dietary histone deacetylase inhibitor, reactivate ER alpha expression in ER alpha-negative MDA-MB-231 cells. Here, we investigated the functional significance of ERa reactivation in the reactivation of silenced tumor suppressor genes (TSGs) in ER alpha-negative human breast cancer cells. We found that the treatment of MDA-MB-231 cells with the combinations of GTPs and SFN leads to the reactivation of silenced TSGs such as p21(CIP1/WAF1) and KLOTHO through active chromatin modifications. Further, GTPs- and SFN-mediated reactivation of TSGs was, at least in part, dependent on ERa reactivation in ERa-negative MDA-MB-231 cells. Collectively, our findings suggest that a novel combination of bioactive dietary supplements could further be explored as an effective therapeutic option against hormonal refractory breast cancer. (C) 2015 Elsevier Ireland Ltd. All rights reserved.