title: Heparan/chondroitin/dermatan sulfate primer 2-(6-hydroxynaphthyl)-O-beta-D-xylopyranoside preferentially inhibits growth of transformed cells.
abstract: Xylose forms the direct carbohydrate-protein link in extra- or pericellular proteoglycans (PGs) that are substituted with either chondroitin sulfate (CS)/dermatan sulfate (DS) and/or heparan sulfate (HS). Cell surface PGs carrying HS are important regulators of cell growth. Xylose coupled to an aromatic compound can enter cells and initiate either CS/DS synthesis or both HS and CS/DS synthesis, depending on the nature of the aromatic adduct. Here, we show that 2-(6-hydroxynaphthyl)-O-beta-D-xylopyranoside, which can prime both types of glycan chains, inhibits growth of a set of normal and transformed cells. Transformed cells are preferentially inhibited, and at a concentration of 0.15-0.20 mM xyloside, transformed cells are totally growth arrested, whereas normal cells are only < or = 50% inhibited. No inhibition of growth is observed with the stereoisomeric 2-(6-hydroxynaphthyl)-O-beta-L-xylopyranoside, which does not prime glycosaminoglycan synthesis at all; with the nonhydroxylated 2-naphthyl-O-beta-D-xylopyranoside, which only primes CS/DS synthesis under these conditions; or with p-nitrophenyl-O-beta-D-xylopyranoside, which is known to prime only CS/DS synthesis. We conclude that growth inhibition is due to priming of HS and/or CS/DS synthesis, which may either lead to the formation of specific antiproliferative glycans or glycan fragments or to interference with endogenous PG synthesis and turnover.
authors.affiliation: Department of Cell Biology and Molecular Biology, Lund University, Sweden. Katrin.Mani@medkem.lu.se
authors.forename: K
authors.initials: K
authors.lastname: Mani
authors.forename: B
authors.initials: B
authors.lastname: Havsmark
authors.forename: S
authors.initials: S
authors.lastname: Persson
authors.forename: Y
authors.initials: Y
authors.lastname: Kaneda
authors.forename: H
authors.initials: H
authors.lastname: Yamamoto
authors.forename: K
authors.initials: K
authors.lastname: Sakurai
authors.forename: S
authors.initials: S
authors.lastname: Ashikari
authors.forename: H
authors.initials: H
authors.lastname: Habuchi
authors.forename: S
authors.initials: S
authors.lastname: Suzuki
authors.forename: K
authors.initials: K
authors.lastname: Kimata
authors.forename: A
authors.initials: A
authors.lastname: Malmström
authors.forename: G
authors.initials: G
authors.lastname: Westergren-Thorsson
authors.forename: L A
authors.initials: LA
authors.lastname: Fransson
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002809:Chondroitin Sulfates / Q000096:biosynthesis*; D003871:Dermatan Sulfate / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000166:cytology; D006027:Glycosides / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D009284:Naphthols / Q000494:pharmacology*; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects*
chemical_list: C111149:2-(6-hydroxynaphthyl)-O-beta-D-xylopyranoside; D006027:Glycosides; D006131:Growth Inhibitors; D009284:Naphthols; C010807:xylosides; D003871:Dermatan Sulfate; D002809:Chondroitin Sulfates