Abstract
Expression of estrogen receptor beta (ER beta) has been described to reduce growth of cancer cell lines derived from hormone-dependent tumors, like breast cancer. In this study we tested to what extent two ER beta agonists, androgen derivative 3 beta-Adiol and flavonoid Liquiritigenin, would affect growth and gene expression of different ER beta-positive human breast cancer cell lines. Under ...
Abstract
Expression of estrogen receptor beta (ER beta) has been described to reduce growth of cancer cell lines derived from hormone-dependent tumors, like breast cancer. In this study we tested to what extent two ER beta agonists, androgen derivative 3 beta-Adiol and flavonoid Liquiritigenin, would affect growth and gene expression of different ER beta-positive human breast cancer cell lines. Under standard cell culture conditions, we observed 3 beta-Adiol to inhibit growth of MCF-7 cells in a dose-dependent manner, whereas growth of BT-474 and MCF-10A cells was suppressed by the maximum concentration (100 nM) only. When treated in serum-free medium, all cell lines except of MDA-MB-231 were responsive to 1 nM 3 beta-Adiol, and ZR75-1 cells exhibited a dose-dependent antiproliferative response. Providing putative mechanisms underlying the observed growth-inhibitory effect, expression of Ki-67 or cyclins A2 and B1 was downregulated after 3 beta-Adiol treatment in all responsive lines. In contrast, treatment with lower doses of Liquiritigenin did not affect growth. In MCF-7 cells, the highest dose of this flavonoid exerted proliferative effects accompanied by increased expression of cyclin B1, PR and PS2, indicating unspecific activation of ER alpha. In conclusion, the ER beta agonists tested exerted distinct concentration-dependent and cell line-specific effects on growth and gene expression. The observed inhibitory effects of 3 beta-Adiol on breast cancer cell growth encourage further studies on the potential of this and other ER beta agonists as targeted drugs for breast cancer therapy. (C) 2012 Elsevier Inc. All rights reserved.
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