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Title: Mechanism-based inhibition of cancer metastasis with (−)-epigallocatechin gallate

Highlights: •EGCG reduced cell motility of highly metastatic human lung cancer cells. •EGCG increased cell stiffness of the cells, indicating the inhibition of phenotypes of EMT. •EGCG inhibited expression of vimentin and Slug in the cells at the leading edge of scratch. •Treatment of MβCD increased cell stiffness, and inhibited cell motility and vimentin expression. •Inhibition of EMT phenotypes with EGCG is a mechanism-based inhibition of cancer metastasis. -- Abstract: Cell motility and cell stiffness are closely related to metastatic activity of cancer cells. (−)-Epigallocatechin gallate (EGCG) has been shown to inhibit spontaneous metastasis of melanoma cell line into the lungs of mice, so we studied the effects of EGCG on cell motility, cell stiffness, and expression of vimentin and Slug, which are molecular phenotypes of epithelial–mesenchymal transition (EMT). Treatments of human non-small cell lung cancer cell lines H1299 and Lu99 with 50 and 100 μM EGCG reduced cell motility to 67.5% and 43.7% in H1299, and 71.7% and 31.5% in Lu99, respectively in in vitro wound healing assay. Studies on cell stiffness using atomic force microscope (AFM) revealed that treatment with 50 μM EGCG increased Young’s modulus of H1299 from 1.24 to 2.25 kPa and that of Lu99 frommore » 1.29 to 2.28 kPa, showing a 2-fold increase in cell stiffness, i.e. rigid elasticity of cell membrane. Furthermore, treatment with 50 μM EGCG inhibited high expression of vimentin and Slug in the cells at a leading edge of scratch. Methyl-β-cyclodextrin, a reagent to deplete cholesterol in plasma membrane, showed inhibition of EMT phenotypes similar that by EGCG, suggesting that EGCG induces inhibition of EMT phenotypes by alteration of membrane organization.« less
Authors:
 [1] ;  [2] ;  [2] ; ; ; ;  [1] ; ;  [1] ;  [2] ;  [1] ;  [1]
  1. Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama 362-0806 (Japan)
  2. (Japan)
Publication Date:
OSTI Identifier:
22242231
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 443; Journal Issue: 1; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ATOMIC FORCE MICROSCOPY; CELL MEMBRANES; CHOLESTEROL; FLEXIBILITY; HEALING; IN VITRO; INHIBITION; LUNGS; MELANOMAS; METASTASES; MICE; OLIGOSACCHARIDES; PHENOTYPE; WOUNDS