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.
METHODS
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.


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 αγβ3 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.


CONCLUSIONS
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.
Hsu
Ya-Ling
YL
Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Wu
Ling-Yu
LY
Hou
Ming-Feng
MF
Tsai
Eing-Mei
EM
Lee
Jau-Nan
JN
Liang
Hsin-Lin
HL
Jong
Yuh-Jyh
YJ
Hung
Chih-Hsing
CH
Kuo
Po-Lin
PL
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D054443:Cell Migration Assays; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D006035:Glycyrrhiza / Q000737:chemistry*; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D010636:Phenols / Q000494:pharmacology* / Q000627:therapeutic use; D018517:Plant Roots / Q000737:chemistry*; D011897:Random Allocation; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors*
D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D007529:Isoflavones; D010636:Phenols; C066737:RHOA protein, human; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020742:rhoA GTP-Binding Protein; C107601:glabridin