Journal
MOLECULAR AND CELLULAR BIOCHEMISTRY
Volume 366, Issue 1-2, Pages 111-122Publisher
SPRINGER
DOI: 10.1007/s11010-012-1288-9
Keywords
Estrogen receptor beta; Breast cancer; MCF-7 cell; Trichostatin A; Raloxifene
Categories
Funding
- Natural Science Foundation Committee of China [NSFC 30672015, 30700779, 30800257, 30970776, 81000666, 81071194, 31050110123]
- Ministry of Science and Technology for new drug development [2009ZX09310-004]
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Antiestrogen is one type of the endocrine therapeutic agents for estrogen receptor alpha (ER alpha)-positive breast cancer. Unfortunately, this treatment alone is insufficient. Here we reported a novel potential anticancer strategy by using histone deacetylase (HDAC) inhibitor to enhance the action of endocrine therapy in ER alpha-positive breast cancer cell. The well-described HDAC inhibitor, trichostatin A (TSA), and antiestrogen raloxifene were found to, respectively, inhibit E2-induced proliferation of MCF-7 breast cancer cell in a dose-responsive and time-dependent manner. TSA and raloxifene enhanced the antiproliferative activity of each other by promoting cell death via apoptosis and cell cycle arrest. Thus, they displayed better antiproliferative effects in combined treatment than that with either agent alone. The expression level of estrogen receptor beta (ER beta) showed a marked increase after TSA or/and raloxifene treatment. Treatments with TSA or/and raloxifene resulting in the up-regulation of ER beta are in accordance with the antiproliferative effects of the two agents. Furthermore, the over-expression of ER beta by adenovirus delivery could inhibit the proliferation of MCF-7 tumor cells and drastically enhanced the antiproliferative effects of TSA and raloxifene. These results demonstrated that the interference of ER beta on the antiproliferative effects of HDAC inhibitor and antiestrogen constitutes a promising approach for breast cancer treatment.
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