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

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Mani, KLund University,Lunds universitet,Glykobiologigruppen,Forskargrupper vid Lunds universitet,Glycobiology,Lund University Research Groups (author)

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.

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Cell- och molekylärbiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Cell and Molecular Biology hsv//eng
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

Havsmark, BLund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine(Swepub:lu)medk-bha (author)
Persson, SusanneLund University (author)
Kaneda, Y (author)
Yamamoto, H (author)
Sakurai, K (author)
Ashikari, S (author)
Habuchi, H (author)
Suzuki, S (author)
Kimata, K (author)
Malmström, ALund University,Lunds universitet,Matrixbiologi,Forskargrupper vid Lunds universitet,Matrix Biology,Lund University Research Groups(Swepub:lu)medk-ama (author)
Westergren-Thorsson, GLund University,Lunds universitet,Lungbiologi,Forskargrupper vid Lunds universitet,Lung Biology,Lund University Research Groups(Swepub:lu)medk-gwt (author)
Fransson, L ALund University,Lunds universitet,Glykobiologigruppen,Forskargrupper vid Lunds universitet,Glycobiology,Lund University Research Groups(Swepub:lu)medk-laf (author)
GlykobiologigruppenForskargrupper vid Lunds universitet (creator_code:org_t)

By the author/editor: Mani, K; Havsmark, B; Persson, Susanne; Kaneda, Y; Yamamoto, H; Sakurai, K; show more...; Ashikari, S; Habuchi, H; Suzuki, S; Kimata, K; Malmström, A; Westergren-Thors ...; Fransson, L A; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

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