The Anti-Proliferative Effects of Enterolactone in Prostate Cancer Cells: Evidence for the Role of DNA Licencing Genes, mi-R106b Cluster Expression, and PTEN Dosage
The Anti-Proliferative Effects of Enterolactone in Prostate Cancer Cells: Evidence for the Role of DNA Licencing Genes, mi-R106b Cluster Expression, and PTEN Dosage
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DOI：
10.3390/nu6114839
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发表时间：
2014-11-01
期刊：
影响因子：
5.9
通讯作者：
Roy, Nicole C.
中科院分区：
文献类型：
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作者：
McCann, Mark J.;Rowland, Ian R.;Roy, Nicole C.
哺乳动物木脂素，肠内酯，已被证明在体外生理浓度下减少前列腺癌早期阶段的增殖。然而，在疾病的后期阶段，通过饮食调整难以达到的浓度会产生疗效。因此，我们使用前列腺疾病的体外模型系统研究了什么浓度的肠内酯可以限制多个阶段的前列腺癌的增殖。我们确定，肠内酯在20 μ M显着限制前列腺疾病的中期和晚期模型的增殖。这些效应与DNA许可基因（GMNN、CDT 1、MCM 2和7）表达的变化、miR-106 b簇（miR-106 b、miR-93和miR-25）表达的减少以及PTEN肿瘤抑制基因表达的增加密切相关。我们已经证明肠内酯在前列腺疾病的早期阶段比以前报道的抗增殖作用，这些作用是介导的，部分是由microRNA介导的调节。
The mammalian lignan, enterolactone, has been shown to reduce the proliferation of the earlier stages of prostate cancer at physiological concentrations in vitro. However, efficacy in the later stages of the disease occurs at concentrations difficult to achieve through dietary modification. We have therefore investigated what concentration(s) of enterolactone can restrict proliferation in multiple stages of prostate cancer using an in vitro model system of prostate disease. We determined that enterolactone at 20 mu M significantly restricted the proliferation of mid and late stage models of prostate disease. These effects were strongly associated with changes in the expression of the DNA licencing genes (GMNN, CDT1, MCM2 and 7), in reduced expression of the miR-106b cluster (miR-106b, miR-93, and miR-25), and in increased expression of the PTEN tumour suppressor gene. We have shown anti-proliferative effects of enterolactone in earlier stages of prostate disease than previously reported and that these effects are mediated, in part, by microRNA-mediated regulation.