Abstract 5758: Elevated level of estrogen enhances chemotherapeutic efficacy potentially through epigenetic mechanism in human breast cancer cells

Abstract Effectiveness of chemotherapy depends on the age of breast cancer patients. Breast tissues are estrogen sensitive and the levels of ovarian estrogen are age-dependent variable among the breast cancer patients. Whether this variation in estrogen levels influences the chemotherapeutic efficacy in breast cancer patients is unclear. Therefore, the objective of this study was to determine the effects of natural estrogen 17 beta-estradiol on the efficacy of chemotherapy in breast cancer cells. Estrogen responsive MCF-7 breast cancer cells were long-term exposed to 100 pg/ml estrogen for three months. Using these estrogen exposed MCF-7 cells, the efficacy of chemotherapeutic drugs doxorubicin and cisplatin were determined. The result of cell viability and cell cycle analysis revealed increased efficacy of doxorubicin and cisplatin in estrogen-exposed MCF-7 cells as compared to control MCF-7 cells. Gene expression analysis of marker genes for cell cycle, anti-apoptosis, DNA repair, and drug transporter genes further confirmed the increased efficacy of chemotherapeutic drugs in estrogen-exposed cells at molecular level. To further understand the role of epigenetic mechanism in enhanced chemotherapeutic efficacy by estrogen, cells were pre-treated with epigenetic drugs, 5-Aza-2-deoxycytidine and Trichostatin A before doxorubicin and cisplatin treatments. The enhanced efficacy of doxorubicin and cisplatin in estrogen-treated cells was significantly decreased by 5-aza-2 deoxycytidine pre-treatment, suggesting the role of estrogen-induced hypermethylation in enhanced sensitivity of these drugs in estrogen-exposed cells. In conclusion, results of this study demonstrate that sensitivity to chemotherapy depends on the levels of estrogen in breast cancer cells. Findings of this study will have clinical implications in selecting the type and dose of chemotherapy in breast cancer patients depending on the serum estrogen levels that varies in between pre- and post-menopausal age of the patients. Citation Format: Yu-Wei Chang, Kamaleshwar Singh. Elevated level of estrogen enhances chemotherapeutic efficacy potentially through epigenetic mechanism in human breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5758. doi:10.1158/1538-7445.AM2017-5758