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Epigallocatechin-3 gallate inhibits cancer invasion by repressing functional invadopodia formation in oral squamous cell carcinoma

 Young Sun Hwang  ;  Kwang-Kyun Park  ;  Won-Yoon Chung 
 European Journal of Pharmacology, Vol.715(1-3) : 286-295, 2013 
Journal Title
 European Journal of Pharmacology 
Issue Date
Animals ; Antineoplastic Agents/pharmacology* ; Carcinoma, Squamous Cell/pathology* ; Catechin/analogs & derivatives* ; Catechin/pharmacology ; Cell Membrane/drug effects* ; Cell Membrane/pathology* ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Cortactin/metabolism ; Extracellular Matrix/drug effects ; Extracellular Matrix/metabolism ; Focal Adhesion Kinase 1/metabolism ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Male ; Matrix Metalloproteinases/metabolism ; Mice ; Mice, Inbred BALB C ; Mouth Neoplasms/pathology* ; Neoplasm Invasiveness ; Phosphorylation/drug effects ; Proto-Oncogene Proteins pp60(c-src)/metabolism ; Xenograft Model Antitumor Assays ; rhoA GTP-Binding Protein/metabolism
Cortactin ; EGCG ; FAK ; Invadopodia formation ; RhoA activation ; Src
Although the polyphenol EGCG has various beneficial biological effects, its effect on cytoskeletal activities during cancer invasion is not well defined, and the precise molecular mechanisms are largely unknown. Here, we provide molecular evidence on the anti-invasion effect of EGCG in OSCC cells using an in vitro 3-D culture system and in vivo athymic mouse model. Briefly, EGCG exerted an inhibitory effect on the Matrigel-based Transwell invasion and migration of OSCC cells. These effects were not due to decreased cell viability or adhesion capacity to ECM. EGCG-treated OSCC cells possessed fully extended actin fibers without invadopodia, indicating a loss of ECM degradation capacity. Decreased phosphorylation of Src, CTTN, and FAK also followed EGCG treatment. Additionally, EGCG reduced activation of RhoA in dominant-negative RhoA N19 and constitutively active RhoA Q63E cells, and inhibited the invasive capability of these cells in the 3-D cell growth model. Furthermore, the administration of EGCG led to substantial inhibition of tumor growth and activation of invadopodial proteins in the tumor tissues of mice inoculated with OSCC cells. The data indicate the potential value of EGCG as an invadopodia-targeted anti-invasive agent in cancer therapy.
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2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Park, Kwang Kyun(박광균)
Chung, Won Yoon(정원윤) ORCID logo https://orcid.org/0000-0001-8428-9005
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