Glabridin inhibits migration, invasion, and angiogenesis of human non-small cell lung cancer A549 cells by inhibiting the FAK/rho signaling pathway.
This study reports the antimigration, anti-invasive effect of glabridin, a flavonoid obtained from licorice, in human non-small cell lung cancer A549 cells. Glabridin exhibited effective inhibition of cell metastasis by decreasing cancer cell migration and invasion of A549 cells. In addition, glabridin also decreased A549-mediated angiogenesis. Further investigation revealed that glabridin's inhibition of cancer angiogenesis was also evident in a nude mice model. Blockade of A549 cells migration was associated with an increase of ανβ3 integrin proteosome degradation. Glabridin also decreased the active forms of FAK and Src, and enhanced levels of inactivated phosphorylated Src (Tyr 527), decreasing the interaction of FAK and Src. Inhibition of the FAK/Src complex by glabridin also blocked Akt activation, resulting in reduced activation of RhoA and myosin light chain phosphorylation. This study demonstrates that glabridin may be a novel anticancer agent for the treatment of lung cancer in 3 different ways: inhibition of migration, invasion, and angiogenesis.
Division of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Ying-Ming
YM
Tsai
Chih-Jen
CJ
Yang
Ya-Ling
YL
Hsu
Ling-Yu
LY
Wu
Yu-Chieh
YC
Tsai
Jen-Yu
JY
Hung
Chi-Tun
CT
Lien
Ming-Shyan
MS
Huang
Po-Lin
PL
Kuo
D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D039661:Integrin beta3 / Q000187:drug effects / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D018994:Myosin Light Chains / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000201:enzymology / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D020742:rhoA GTP-Binding Protein / Q000187:drug effects* / Q000378:metabolism; D019061:src-Family Kinases / Q000187:drug effects / Q000378:metabolism
D039661:Integrin beta3; D007529:Isoflavones; D018994:Myosin Light Chains; D010636:Phenols; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019061:src-Family Kinases; D020742:rhoA GTP-Binding Protein; C107601:glabridin