Heparan/chondroitin/dermatan sulfate primer 2-(6-hydroxynaphthyl)-O-beta-D-xylopyranoside preferentially inhibits growth of transformed cells

Research output: Contribution to journalArticle

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.

Details

Authors
Organisations
External organisations
  • Lund University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology

Keywords

  • 3T3 Cells, Animals, Chondroitin Sulfates, Dermatan Sulfate, Endothelium, Vascular, Glycosides, Growth Inhibitors, Humans, Mice, Naphthols, Stereoisomerism, Tumor Cells, Cultured, Journal Article, Research Support, Non-U.S. Gov't
Original languageEnglish
Pages (from-to)1099-104
Number of pages6
JournalCancer Research
Volume58
Issue number6
Publication statusPublished - 1998 Mar 15
Publication categoryResearch
Peer-reviewedYes