title: The anti-cancer effects of (-)-epigallocatechin-3-gallate on the signaling pathways associated with membrane receptors in MCF-7 cells.
abstract: (-)-Epigallocatechin-3-gallate (EGCg) has been implicated in cancer chemo-prevention in studies using many different kinds of cancer cells. The present study measured cell viability, osteopontin (OPN) secretion, fatty acid synthase (FAS) expression, and cytosolic Ca(2+) and verified the anti-cancer activities of EGCg in MCF-7 human breast cancer cells. EGCg-induced apoptosis was evidenced by nuclear condensation, increased protein levels of activated caspase-3, down-regulation of gelsolin and tropomyosin-4 (Tm-4), and up-regulation of tropomyosin-1(Tm-1). By disrupting adherens junction formation, EGCg caused accumulation of extra-nuclear β-catenin aggregates in the cytosol and alterations of the protein content and mRNA expression of E-cadherin and β-catenin, but not N-cadherin, in MCF-7 cells. To identify the putative mechanisms underlying the EGCg signaling pathways, EGFP (enhanced green fluorescence protein) was ectopically expressed in MCF-7 cells. This allowed us to monitor the EGCg-induced fluorescence changes associated with the effects of Triton X-100 (to remove plasma membrane) or the addition of laminin, anti-laminin receptor (LR) antibody, epidermal growth factor (EGF), and genistein on the cells. Our results indicated that EGCg acts via the signaling pathways associated with cell membrane to suppress cell proliferation, provoke apoptosis, and disturb cell-cell adhesion in MCF-7 cells. The altered events include the EGFR, LR, FAS, intracellular Ca(2+) , OPN secretion, caspace-3, gelsolin, Tm-4, Tm-1, and adherens junction proteins, E-cadherin and β-catenin.
authors.affiliation: Department of Life Sciences, National Chung-Hsing University, Taichung, Taiwan.
authors.forename: Yuan-Chang
authors.initials: YC
authors.lastname: Hsu
authors.forename: Ying-Ming
authors.initials: YM
authors.lastname: Liou
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D016588:Anticarcinogenic Agents; D008565:Membrane Proteins; D002392:Catechin; C045651:epigallocatechin gallate; D002118:Calcium