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The enhanced antiproliferative response to combined treatment of trichostatin A with raloxifene in MCF-7 breast cancer cells and its relevance to estrogen receptor β expression

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Abstract

Antiestrogen is one type of the endocrine therapeutic agents for estrogen receptor α (ERα)-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 ERα-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 β (ERβ) showed a marked increase after TSA or/and raloxifene treatment. Treatments with TSA or/and raloxifene resulting in the up-regulation of ERβ are in accordance with the antiproliferative effects of the two agents. Furthermore, the over-expression of ERβ 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 ERβ on the antiproliferative effects of HDAC inhibitor and antiestrogen constitutes a promising approach for breast cancer treatment.

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Acknowledgments

We thank Dr. Guowei Gu (Calabria, Italy) for the gift of Plasmid pCMV5-hERβ. We are also grateful to Professor Tao Xi (Nanjing, China) for the supports during this study. This research was supported by the Natural Science Foundation Committee of China (NSFC 30672015, 30700779, 30800257, 30970776, 81000666, 81071194, 31050110123) and the major project from the Ministry of Science and Technology for new drug development (2009ZX09310-004).

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The authors have no conflicts to disclose.

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Authors and Affiliations

  1. Department of Biomedical Engineering, School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, People’s Republic of China

    Zhenzhen Tu, Hui Li, Yuxiang Ma, Bin Tang, Junmei Tian & Yueqing Gu

  2. Department of Radiology, School of Medicine, Washington University in St. Louis, St. Louis, MO, 63110, USA

    Walter Akers & Samuel Achilefu

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  1. Zhenzhen Tu
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Correspondence to Yueqing Gu.

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Tu, Z., Li, H., Ma, Y. et al. The enhanced antiproliferative response to combined treatment of trichostatin A with raloxifene in MCF-7 breast cancer cells and its relevance to estrogen receptor β expression. Mol Cell Biochem 366, 111–122 (2012). https://doi.org/10.1007/s11010-012-1288-9

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