Glabridin, an isoflavan from licorice root, inhibits migration, invasion and angiogenesis of MDA-MB-231 human breast adenocarcinoma cells by inhibiting focal adhesion kinase/Rho signaling pathway
Glabridin, an isoflavan from licorice root, inhibits migration, invasion and angiogenesis of MDA-MB-231 human breast adenocarcinoma cells by inhibiting focal adhesion kinase/Rho signaling pathway
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DOI：
10.1002/mnfr.201000148
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发表时间：
2011-02-01
影响因子：
5.2
通讯作者：
Kuo, Po-Lin
中科院分区：
文献类型：
--
作者：
Hsu, Ya-Ling;Wu, Ling-Yu;Kuo, Po-Lin
范围：本研究首次报道了从甘草中提取的黄酮类成分光滑素对人乳腺癌细胞MDA-MB-231的侵袭、侵袭和侵袭作用。方法和结果：光滑素通过减少癌细胞的迁移和侵袭，有效地抑制了细胞的转移。此外，光滑素还可阻断人脐静脉内皮细胞(HUVEC)的迁移，减少MDA-MB-231介导的血管生成。进一步的研究表明，在裸鼠模型中，光滑霉素对肿瘤血管生成的抑制作用也很明显。阻断MDA-MB-231细胞和HUVEC迁移与α-γ-β3整合素蛋白小体降解增加有关。Glabridin还降低了FAK和Src的活性形式，并增加了失活的磷酸化Src(Tyr 416)的水平，从而减少了FAK和Src的相互作用。通过抑制FAK/Src复合体的表达，还可以阻断AKT和ERK1/2的激活，从而降低RhoA的活性和肌球蛋白轻链的磷酸化水平。结论：本研究从抑制肿瘤转移、侵袭和血管生成三个方面证实了光滑蛋白可能是一种新型的抗癌药物。
Scope: In this study we first report the antimigration, antiinvasive effect of glabridin, a flavonoid obtained from licorice, in MDA-MB-231 human breast adenocarcinoma cells.Methods and results: Glabridin exhibited effective inhibition of cell metastasis by decreasing cancer cell migration and invasion of MDA-MB-231 cells. In addition, glabridin also blocked human umbilical vein endothelial cells (HUVEC) migration and decreased MDA-MB-231-mediated angiogenesis. Further investigation revealed that the inhibition of cancer angiogenesis by glabridin was also evident in a nude mice model. Blockade of MDA-MB-231 cells and HUVEC migration was associated with an increase of alpha gamma beta 3 integrin proteosome degradation. Glabridin also decreased the active forms of FAK and Src, and enhanced levels of inactivated phosphorylated Src (Tyr 416), decreasing the interaction of FAK and Src. Inhibition of the FAK/Src complex by glabridin also blocked AKT and ERK1/2 activation, resulting in reduced activation of RhoA as well as myosin light chain phosphorylation.Conclusion: This study demonstrates that glabridin may be a novel anticancer agent for the treatment of breast cancer in three different ways: inhibition of migration, invasion and angiogenesis.