title: Epigallocatechingallate inhibits migration of human uveal melanoma cells via downregulation of matrix metalloproteinase-2 activity and ERK1/2 pathway.
abstract: The effects of epigallocatechingallate (EGCG) on the migration and expression of MMP-2 of uveal melanoma cells have not been reported. We studied this effect and relevant signaling pathways in a human uveal melanoma cell line (M17). MTT study found that EGCG did not affect the cell viability of M17 cells up to 100 µM. Wound-healing assay showed that EGCG significantly reduced the migration of melanoma cells in a dose-dependent manner from 20 to 100 µM. Gelatin zymography showed that secreted MMP-2 activity was dose-dependently inhibited by EGCG, whereas the MMP-2 expression at protein and mRNA levels was not affected as determined by western blot and RT-PCR analysis. EGCG significantly increased the expressions of MMP-2 endogenous inhibitors (TIMP-2 and RECK) in M17 cells. Western blot analysis of MAPK signal pathways showed that EGCG significantly decreased phosphorylated ERK1/2 levels, but not p38 and JNK levels, in melanoma cells. ERK1/2 inhibitors also reduced the migration and activity of MMP-2 in M17 cells. The present study suggested EGCG at nontoxic levels could inhibit migration of melanoma cells via downregulation of activities of secreted MMP-2 through the inhibition of the ERK1/2 phosphorylation. Therefore, EGCG may be a promising agent to be explored for the prevention of metastasis of uveal melanoma.
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan ; Department of Ophthalmology, Chung Shan Medical University Hospital, Taichung 40201, Taiwan.
authors.forename: Chi-Wu
authors.initials: CW
authors.lastname: Chang
authors.affiliation: Department of Biochemistry, School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan ; Institute of Biochemistry and Biotechnology, College of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan ; Department of Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 40201, Taiwan.
authors.forename: Yi-Hsien
authors.initials: YH
authors.lastname: Hsieh
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan.
authors.forename: Wei-En
authors.initials: WE
authors.lastname: Yang
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan ; Department of Medical Research, Chung Shan Medical University Hospital, Taichung 40201, Taiwan.
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
authors.affiliation: Tissue Culture Center, New York Eye and Ear Infirmary of Mount Sinai, 310 E. 14th Street, New York, NY 10003, USA.
authors.forename: Yueqin
authors.identifier: 0000-0001-8872-2910
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Tissue Culture Center, New York Eye and Ear Infirmary of Mount Sinai, 310 E. 14th Street, New York, NY 10003, USA.
authors.forename: Dan-Ning
authors.identifier: 0000-0002-7046-8739
authors.initials: DN
authors.lastname: Hu
mesh_terms: D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000378:metabolism; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D010766:Phosphorylation; D014604:Uveal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D000098943:Uveal Melanoma
chemical_list: D002392:Catechin; C045651:epigallocatechin gallate; D020778:Matrix Metalloproteinase 2