کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2195850 | 1550872 | 2015 | 13 صفحه PDF | دانلود رایگان |
• Dietary combinations of DNMT and HDAC inhibitors induce significant cell cycle arrest than the standard inhibitors.
• Combinations of GTPs and SFN reactivate tumor suppressor genes (TSGs) in MDA-MB-231 cells.
• The reactivations of TSGs are mainly mediated through the active chromatin modifications.
• Reactivation of TSGs is partially dependent on estrogen receptor-α (ERα) reactivation in ERα-negative breast cancer cells.
• The reactivation of silenced ERα sensitizes cells for the tamoxifen therapy.
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 ERα expression in ERα-negative MDA-MB-231 cells. Here, we investigated the functional significance of ERα reactivation in the reactivation of silenced tumor suppressor genes (TSGs) in ERα-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 p21CIP1/WAF1 and KLOTHO through active chromatin modifications. Further, GTPs- and SFN-mediated reactivation of TSGs was, at least in part, dependent on ERα reactivation in ERα-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.
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Journal: Molecular and Cellular Endocrinology - Volume 406, 5 May 2015, Pages 102–114