title: Multifunctional effect of epigallocatechin-3-gallate (EGCG) in downregulation of gelatinase-A (MMP-2) in human breast cancer cell line MCF-7.
abstract: OBJECTIVE
  The tumor inhibiting property of green tea polyphenol epigallocatechin-3-gallate (EGCG) is well documented. Studies reveal that matrix-metalloproteinases (MMPs) play pivotal roles in tumor invasion through degradation of basement membranes and extracellular matrix (ECM). We studied the effect of EGCG on matrixmetalloproteinases-2 (MMP-2), the factors involved in activation, secretion and signaling molecules that might be involved in the regulation of MMP-2 in human breast cancer cell line, MCF-7.
  
  
  METHODS
  MCF-7 was treated with EGCG (20 muM, 24 h), the effect of EGCG on MMP-2 expression, activity and its regulatory molecules were studied by gelatin zymography, Western blot, quantitative and semi-quantitative real time RT-PCR, immunoflourescence and cell adhesion assay.
  
  
  RESULTS
  EGCG treatment reduced the activity, protein expression and mRNA expression level of MMP-2. EGCG treatment reduced the expression of focal adhesion kinase (FAK), membrane type-1-matrix metalloproteinase (MT1-MMP), nuclear factor-kappa B (NF-kB), vascular endothelial growth factor (VEGF) and reduced the adhesion of MCF-7 cells to ECM, fibronectin and vitronectin. Real time RT-PCR revealed a reduced expression of integrin receptors alpha5, beta1, alphav and beta3 due to EGCG treatment.
  
  
  CONCLUSIONS
  Down regulation of expression of MT1-MMP, NF-kB, VEGF and disruption of functional status of integrin receptors may indicate decreased MMP-2 activation; low levels of FAK expression might indicate disruption in FAK-induced MMP-2 secretion and decrease in activation of phosphatidyl-inositol-3-kinase (PI-3K), extracellular regulated kinase (ERK) indicates probable hindrance in MMP-2 regulation and induction. We propose EGCG as potential inhibitor of expression and activity of pro-MMP-2 by a process involving multiple regulatory molecules in MCF-7.
authors.affiliation: Department of Receptor Biology & Tumor Metastasis, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata-700 026, India.
authors.forename: Triparna
authors.initials: T
authors.lastname: Sen
authors.forename: Shuvojit
authors.initials: S
authors.lastname: Moulik
authors.forename: Anindita
authors.initials: A
authors.lastname: Dutta
authors.forename: Paromita Roy
authors.initials: PR
authors.lastname: Choudhury
authors.forename: Aniruddha
authors.initials: A
authors.lastname: Banerji
authors.forename: Shamik
authors.initials: S
authors.lastname: Das
authors.forename: Madhumita
authors.initials: M
authors.lastname: Roy
authors.forename: Amitava
authors.initials: A
authors.lastname: Chatterjee
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000235:genetics; D051417:Focal Adhesion Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics; D006801:Humans; D016023:Integrins / Q000037:antagonists & inhibitors / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B / Q000378:metabolism; D019096:Vitronectin / Q000235:genetics
chemical_list: D005353:Fibronectins; D016023:Integrins; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D019096:Vitronectin; D002392:Catechin; C045651:epigallocatechin gallate; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases; D020778:Matrix Metalloproteinase 2