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The effects of black cohosh on the regulation of estrogen receptor (ERα) and progesterone receptor (PR) in breast cancer cells

机译:黑升麻对乳腺癌细胞雌激素受体(ERα)和孕激素受体(PR)的调节作用

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摘要

The North American plant Cimicifuga racemosa, also known as black cohosh (BC), is a herb that recently has gained attention for its hormonal effects. As the usage of hormone replacement therapy is declining due to its adverse effects in women with cancer, many are turning to herbal remedies like BC to treat menopausal symptoms. It is crucial to determine whether the effects of BC involve estrogen receptor-alpha (ERα). Previous studies from our laboratory have shown ERα to be a possible molecular target for BC. In this study, we examined the effects of BC (8% triterpene glycosides) alone and in combination with hormones and antihormones on the cellular viability, expression of ERα and progesterone receptor (PR)-A/B, and cytolocalization of ERα in ER (+) and PR-A/B (+) T-47D breast cancer cells. Cells were cultured and proteins were extracted and quantified. Western blot analysis revealed alterations in the expression of ERα and PR after treatment with BC (5–100 µM). BC induced a concentration-dependent decrease in ERα and PR protein levels when compared to the control. Image cytometric analysis with propidium iodide staining was used to enumerate changes in T-47D cell number and viability. A decrease in T-47D cell viability was observed upon treatment with 5–100 µM BC. The ideal concentration of BC (100 µM) was used in combination with hormones and antihormones in an effort to further understand the possible similarities between this compound and other known effectors of ERα and PR. After a 24-hour concomitant treatment with and/or in combination of BC, estradiol, ICI 182, 780, and Tamoxifen, downregulation of ERα and PR protein levels was observed. Delineating the role of BC in the regulation of ERα, PR, as well as its mechanisms of action, may be important in understanding the influence of BC on hormone receptors in breast cancer.
机译:北美植物Cimicifuga racemosa,也称为黑升麻(BC),是一种最近因其荷尔蒙效应而受到关注的草药。由于荷尔蒙替代疗法的使用由于其对癌症女性的不良影响而在减少,因此许多人正在转向诸如BC之类的草药来治疗更年期症状。确定BC的作用是否涉及雌激素受体-α(ERα)是至关重要的。我们实验室的先前研究表明,ERα是BC的可能分子靶标。在这项研究中,我们研究了单独BC(8%三萜糖苷)以及与激素和抗激素联合使用对BC的影响,对ERα和孕激素受体(PR)-A / B的细胞生存力以及ERα在ER中的细胞定位的影响( +)和PR-A / B(+)T-47D乳腺癌细胞。培养细胞,提取蛋白质并定量。 Western印迹分析表明,用BC(5-100 µM)处理后,ERα和PR的表达发生了变化。与对照相比,BC诱导了ERα和PR蛋白水平的浓度依赖性降低。碘化丙锭染色的图像细胞计数分析用于枚举T-47D细胞数量和活力的变化。用5–100 µM BC处理后,观察到T-47D细胞活力降低。理想浓度的BC(100 µM)与激素和抗激素结合使用,以进一步了解该化合物与ERα和PR其他已知效应物之间的可能相似性。用BC,雌二醇,ICI 182、780和他莫昔芬联合治疗24小时后,观察到ERα和PR蛋白水平下调。描述BC在ERα,PR的调节中的作用及其作用机制,可能对理解BC对乳腺癌激素受体的影响很重要。

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