title: In vitro effects of genistein on the synthesis and distribution of glycosaminoglycans/proteoglycans by estrogen receptor-positive and -negative human breast cancer epithelial cells.
abstract: Genistein, a soy isoflavone, affects the proliferation of both estrogen receptor (ER)-positive and ER-negative cancer cells. Glycosaminoglycans (GAGs)/proteoglycans (PGs) are considered to be of great importance in the treatment of cancer. The synthesis of GAGs by two human breast cancer epithelial cell lines, the ER-positive MCF-7 and the ER-negative BT-20, was studied under the effects of genistein, and their distribution in the culture medium and the cell membranes was determined. The results obtained show that both cell lines synthesize extracellular hyaluronic acid (HA) and both extracellular and cell-associated galactosaminoglycans (GalAGs) and heparan sulphate (HS). The MCF-7 cell line synthesizes HA, GalAGs and HS at considerably lower rates than the BT-20 cell line. The effect of genistein on the synthesis of extracellularly secreted GAGs/PGs by ER-positive MCF-7 cells is dose-dependent and follows two mechanisms; one at low concentrations (< or = 35 microM) mediated via the estrogen receptor and the other at higher concentrations via protein tyrosine kinase (PTK). The synthesis of cell-associated GAGs/PGs by ER-positive MCF-7 cells and of both secreted and associated with the cell membrane GAGs/PGs by ER-negative BT-20 cells is mediated by a PTK mechanism. It is concluded that genistein affects the synthesis of GAGs/PGs, by breast cancer epithelial cells depending on the presence or absence of estrogen receptor and the localisation of PGs.
authors.affiliation: Department of Chemistry, Section of Organic Chemistry, Biochemistry and Natural Products, Laboratory of Biochemistry, University of Patras, 265 00 Patras, Greece.
authors.forename: Theoni N
authors.initials: TN
authors.lastname: Mitropoulou
authors.forename: George N
authors.initials: GN
authors.lastname: Tzanakakis
authors.forename: Dragana
authors.initials: D
authors.lastname: Nikitovic
authors.forename: Aristidis
authors.initials: A
authors.lastname: Tsatsakis
authors.forename: Nikos K
authors.initials: NK
authors.lastname: Karamanos
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D019833:Genistein / Q000494:pharmacology*; D005944:Glucosamine / Q000378:metabolism; D006025:Glycosaminoglycans / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D011509:Proteoglycans / Q000096:biosynthesis / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D014316:Tritium; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D006025:Glycosaminoglycans; D011509:Proteoglycans; D011960:Receptors, Estrogen; D014316:Tritium; D019833:Genistein; D005944:Glucosamine