title: Epigallocatechin gallate inhibits growth and epithelial-to-mesenchymal transition in human thyroid carcinoma cell lines.
abstract: Well-differentiated papillary and follicular thyroid carcinoma are the most frequent types of thyroid cancer and the prognosis is generally favorable however, a number of patients develops recurrences. Epigallocatechin-3-gallate (EGCG), a major catechin in green tea, was shown to possess remarkable therapeutic potential against various types of human cancers, although data on thyroid cancer cells are still lacking. The aim of this study was to investigate the effect of EGCG on the proliferation and motility of human thyroid papillary (FB-2) and follicular (WRO) carcinoma cell lines. Our results demonstrate that EGCG (10, 40, 60 μM) treatment inhibited the growth of FB-2 and WRO cells in a dose-dependent manner. These changes were associated with reduced cyclin D1, increased p21 and p53 expression. Furthermore, EGCG suppressed phosphorylation of AKT and ERK1/2. In addition EGCG treatment results in reduction of cell motility and migration. Changes in motility and migration in FB-2 were associated with modulation in the expression of several proteins involved in cell adhesion and reorganization of actin cytoskeleton. After 24 h EGCG caused an increase of the E-cadherin expression and a concomitant decrease of SNAIL, ZEB and the basic helix-loop-helix transcription factor TWIST. Besides expression of Vimentin, N-cadherin and α5-integrin was down-regulated. These data well correlate with a reduction of MMP9 activity as evidenced by gelatin zymography. Our findings support the inhibitory role of EGCG on thyroid cancer cell proliferation and motility with concomitant loss of epithelial-to-mesenchymal cell transition markers.
authors.affiliation: Centro Sanitario, University of Calabria, Calabria, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: De Amicis
authors.forename: Anna
authors.initials: A
authors.lastname: Perri
authors.forename: Donatella
authors.initials: D
authors.lastname: Vizza
authors.forename: Alessandra
authors.initials: A
authors.lastname: Russo
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Panno
authors.forename: Daniela
authors.initials: D
authors.lastname: Bonofiglio
authors.forename: Cinzia
authors.initials: C
authors.lastname: Giordano
authors.forename: Loredana
authors.initials: L
authors.lastname: Mauro
authors.forename: Saveria
authors.initials: S
authors.lastname: Aquila
authors.forename: Donatella
authors.initials: D
authors.lastname: Tramontano
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Andò
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D039482:Integrin alpha5 / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D014746:Vimentin / Q000235:genetics / Q000378:metabolism; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D000199:Actins; D015820:Cadherins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018398:Homeodomain Proteins; D039482:Integrin alpha5; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D051879:Twist-Related Protein 1; D014746:Vimentin; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D019938:Cyclin D1; D002392:Catechin; C045651:epigallocatechin gallate; D051057:Proto-Oncogene Proteins c-akt; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9