Glabridin inhibits cancer stem cell-like properties of human breast cancer cells: An epigenetic regulation of miR-148a/SMAd2 signaling
Glabridin inhibits cancer stem cell-like properties of human breast cancer cells: An epigenetic regulation of miR-148a/SMAd2 signaling
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DOI：
10.1002/mc.22333
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发表时间：
2016-05-01
影响因子：
4.6
通讯作者：
Li, Zhong
中科院分区：
文献类型：
--
作者：
Jiang, Fei;Li, Yuan;Li, Zhong
在乳腺癌中，肿瘤干细胞(CSCs)被认为是转移和复发的主要原因。靶向干细胞或具有干细胞样特性的癌细胞已成为治疗乳腺癌的一种新方法。甘草甜素是一种从光果甘草根中提取的植物化学物质，在多种人类癌细胞中显示出有效的抗肿瘤活性。然而，GLA在调节CSC样属性中的作用和潜在的分子机制仍不清楚。在此，我们报道了GLA在体内外通过microRNA-148A(miR-148A)/转化生长因子-β(TGF)-Smad2信号通路减弱CSC样特性。在MDA-MB-231和HS-578T乳腺癌细胞中，GLA通过DNA去甲基化增强miR-148A的表达。通过靶向Smad2-3-UTR，miR-148A阻断了Smad2的表达/激活，进而恢复了Smad2的上皮特性、黏附能力和CSC样特性。此外，在小鼠异种移植模型中，我们还证实了GLA通过去甲基化激活的miR-148A抑制肿瘤生长、间充质特性和CSCs样特性。我们的发现提示了一种潜在的治疗策略，以减少CSCs样属性，从而提高乳腺癌治疗的有效性。(C)2015年威利期刊公司。
In breast cancer, the cancer stem cells (CSCs) are thought to be the main cause of metastasis and recurrence. Targeting of CSCs or cancer cells with stem cell-like properties has become a new approach for the treatment of breast cancer. Glabridin (GLA), a phytochemical from the root of Glycyrrhiza glabra, exhibited effective antitumor properties in various human cancer cells. However, the roles of GLA in the regulation of CSC-like properties and the underlying molecular mechanisms remain unclear. Here, we reported that GLA attenuated the CSC-like properties through microRNA-148a (miR-148a)/transforming growth factor beta (TGF)-SMAD2 signal pathway in vitro and in vivo. In MDA-MB-231 and Hs-578T breast cancer cell lines, GLA enhanced the expression of miR-148a through DNA demethylation. By targeting of the SMAD2-3-UTR, miR-148a blocked the expression/activation of SMAD2, and in turn, restored the epithelial characteristics, adhesive abilities, and CSC-like properties. Furthermore, in mouse xenograft models, we also confirmed that GLA attenuated the tumor growth, mesenchymal characteristics, and CSCs-like properties via demethylation-activated miR-148a. Our findings suggested a potential treatment strategy to reduce the CSCs-like properties, and therefore enhance the effectiveness of breast cancer therapy. (c) 2015 Wiley Periodicals, Inc.