Epigallocatechin-3-gallate inhibits paracrine and autocrine hepatocyte growth factor/scatter factor-induced tumor cell migration and invasion.
10.3858/emm.2011.43.2.013
- Author:
In hae KWAK
1
;
Yun Hye SHIN
;
Myeongdeok KIM
;
Hyun Young CHA
;
Hyun Ja NAM
;
Bok Soon LEE
;
S C CHAUDHARY
;
Ki Soo PAI
;
Jae Ho LEE
Author Information
1. Department of Biochemistry, Ajou University Medical School, Suwon 443-721, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
autocrine communication;
epigallocatechin gallate;
hepatocyte growth factor;
neoplasm metastasis;
paracrine communication;
proto-oncogene proteins c-met
- MeSH:
Animals;
Autocrine Communication/*drug effects;
Catechin/*analogs & derivatives/metabolism/pharmacology;
Cell Line, Tumor;
Cell Movement/drug effects;
Female;
*Hepatocyte Growth Factor;
Humans;
Mice;
Mice, Inbred BALB C;
Neoplasms, Experimental/*metabolism/pathology;
Paracrine Communication/*drug effects;
Phosphorylation/drug effects;
Proto-Oncogene Proteins c-met/antagonists & inhibitors/metabolism;
Receptors, Growth Factor/antagonists & inhibitors/metabolism;
Signal Transduction
- From:Experimental & Molecular Medicine
2011;43(2):111-120
- CountryRepublic of Korea
- Language:English
-
Abstract:
Aberrant activation of hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, Met, is involved in the development and progression of many human cancers. In the cell-based screening assay, (-)epigallocatechin-3-gallate (EGCG) inhibited HGF/SF-Met signaling as indicated by its inhibitory activity on HGF/SF-induced cell scattering and uPA activation (IC50 = 15.8 microg/ml). Further analysis revealed that EGCG at low doses specifically inhibited HGF/SF-induced tyrosine phosphorylation of Met but not epidermal growth factor (EGF)-induced phosphorylation of EGF receptor (EGFR). On the other hand, high-dose EGCG decreased both Met and EGFR proteins. We also found that EGCG did not act on the intracellular portion of Met receptor tyrosine kinase, i.e., it inhibited InlB-dependent activation of Met but not NGF-induced activation of Trk-Met hybrid receptor. This inhibition decreased HGF-induced migration and invasion by parental or HGF/SF-transfected B16F10 melanoma cells in vitro in either a paracrine or autocrine manner. Furthermore, EGCG inhibited the invasion/metastasis of HGF/SF-transfected B16F10 melanoma cells in mice. Our data suggest the possible use of EGCG in human cancers associated with dysregulated paracrine or autocrine HGF/SF-Met signaling.
