Deoxybenzoins are novel potent selective estrogen receptor modulators

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• 作者：Zoi Papoutsi ; Eva Kassi ; Nikolas Fokialakis ; Sofia Mitakou ; George Lambrinidis ; Emmanuel Mikros ; Paraskevi Moutsatsou
• 关键词：Deoxybenzoins ; Selective estrogen receptor modulator (SERM) ; Estrogen receptor ; Osteoblasts ; Breast cancer cells ; IGFBP-3
• 刊名：Steroids
• 出版年：2007
• 期刊代码：142_0039128x
• 类别：bio
• 出版时间：September 2007
• 卷：72
• 期：9-10
• 页码：693-704
• 文件大小：1023 K

摘要

Deoxybenzoins are plant compounds with similar structure to isoflavones. In this study, we evaluated the ability of two synthesized deoxybenzoins (compound 1 and compound 2) (a) to influence the activity of the estrogen receptor subtypes ERα and ERβ in HeLa cells co-transfected with an estrogen response element-driven luciferase reporter gene and ERα- or ERβ-expression vectors, (b) to modulate the IGFBP-3 and pS2 protein in MCF-7 breast cancer cells, (c) to induce mineralization of KS483 osteoblasts and (d) to affect the cell viability of endometrial (Ishikawa) and breast (MCF-7, MDA-MB-231) cancer cells. Docking and binding energy calculations were performed using the mixed Monte Carlo/Low Mode search method (Macromodel 6.5). Compound 1 displayed significant estrogenic activity via ERβ but no activity via ERα. Compound 2 was an estrogen-agonist via ERα and antagonist via ERβ. Both compounds increased, like the pure antiestrogen ICI182780, the IGFBP-3 levels. Compound 2 induced, like 17β-estradiol, significant mineralization in osteoblasts. The cell viability of Ishikawa cells was unchanged in the presence of either compound. Compound 1 increased MCF-7 cell viability consistently with an increase in pS2 levels, whereas compound 2 inhibited the cell viability. Molecular modeling confirmed the agonistic or antagonistic behaviour of compound 2 via ER subtypes. Compound 2, being an agonist in osteoblasts, an antagonist in breast cancer cells, with no estrogenic effects in endometrial cancer cells, makes it a potential selective estrogen receptor modulator and a choice for hormone replacement therapy.