title: Mechanism-based inhibition of cancer metastasis with (-)-epigallocatechin gallate.
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 from 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.
authors.affiliation: Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama 362-0806, Japan; Graduate School of Science and Engineering, Saitama University, Saitama 338-8570, Japan; Green Tea Laboratory, Saitama Prefectural Agriculture and Forestry Research Center, Saitama 358-0042, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takahashi
authors.affiliation: Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama 362-0806, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama 362-0806, Japan.
authors.forename: Anupom
authors.initials: A
authors.lastname: Mondal
authors.affiliation: Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama 362-0806, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama 362-0806, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Kurusu-Kanno
authors.affiliation: Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama 362-0806, Japan; Graduate School of Science and Engineering, Saitama University, Saitama 338-8570, Japan.
authors.forename: Zhenghao
authors.initials: Z
authors.lastname: Li
authors.affiliation: Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama 362-0806, Japan; Graduate School of Science and Engineering, Saitama University, Saitama 338-8570, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamazaki
authors.affiliation: Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama 362-0806, Japan.
authors.forename: Hirota
authors.initials: H
authors.lastname: Fujiki
authors.affiliation: Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama 362-0806, Japan. Electronic address: masami@cancer-c.pref.saitama.jp.
authors.forename: Masami
authors.initials: M
authors.lastname: Suganuma
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D002784:Cholesterol / Q000378:metabolism; D055119:Elastic Modulus / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D006801:Humans; D051379:Mice; D018625:Microscopy, Atomic Force; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000037:antagonists & inhibitors*; D014746:Vimentin / Q000037:antagonists & inhibitors*; D047392:beta-Cyclodextrins / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; C000604407:SNAI1 protein, human; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D014746:Vimentin; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D002392:Catechin; D002784:Cholesterol; C045651:epigallocatechin gallate
keywords: AFM; Cell migration; EMT; Green tea catechin; MβCD; Vimentin