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

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.