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Glycoconjugate Journal

, Volume 16, Issue 3, pp 237–245 | Cite as

3′-Azidothymidine significantly alters glycosphingolipid synthesis in melanoma cells and decreases the shedding of gangliosides

  • R. Steet
  • M. Alizadeh
  • P. Melançon
  • R. D. Kuchta
Article

Abstract

In this report, we establish that 3′-azido-3′-deoxythymidine (AZT) treatment of melanoma cells greatly alters the pattern of glycosphingolipid biosynthesis. In SK-MEL-30 cells, synthesis of the gangliosides GM3 and GD3 was significantly inhibited (60% and 50% of control, respectively) and the production of their precursor, lactosylceramide, was stimulated by 2.5-fold. Control experiments established that phospholipid synthesis was not affected by AZT treatment, consistent with AZT treatment only affecting lipid biosynthetic reactions that involve glycosylation. Likely as a consequence of decreased rates of ganglioside synthesis, AZT treatment of SK-MEL-30 cells also significantly suppressed the amount of gangliosides shed from the membranes of these cells. Since shedding of gangliosides has been proposed to allow melanoma cells to avoid destruction by the immune system and alterations of glycosphingolipid levels are likely important for the malignant cell phenotype, these results may have important implications regarding the potential use of AZT or related glycosylation inhibitors as cancer chemotherapeutics.

melanoma AZT cancer ganglioside 

Abbreviations

AZT

3′-azido-3′-deoxythymidine

Cer

ceramide

Crbr

cerebroside

Gal

galactose

GalNAc

N-acetylgalactosamine

Glc

glucose

GlcNAc

N-acetylglucosamine

GD3

disialyl lactosylceramide

GM3

sialyl lactosylceramide

HPTLC

high-performance thin layer chromatography

LacCer

lactosylceramide

MTT

3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide

NeuAc

N-acetylneuraminic acid

PA

phosphatidic acid

PBS

phosphate-buffered saline

PC

phosphatidylcholine

PDMP

1-phenyl-2-decanoylamino-3-morpholino-1-propanol

PE

phosphatidylethanolamine

PI

phosphatidylinositol

PS

phosphatidylserine

SM

sphingomyelin

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Copyright information

© Kluwer Academic Publishers 1999

Authors and Affiliations

  • R. Steet
    • 1
    • 2
  • M. Alizadeh
    • 1
    • 2
  • P. Melançon
    • 1
    • 2
  • R. D. Kuchta
    • 1
    • 2
  1. 1.Department of Chemistry and BiochemistryUniversity of ColoradoBoulder
  2. 2.Department of Cell Biology and AnatomyUniversity of AlbertaEdmonton

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