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Tunicamycin treatment reduces intracellular glutathione levels: effect on the metastatic potential of the rhabdomyosarcoma cell line S4MH.

Abstract
Highly metastatic cells are known to overexpress certain Asn-linked oligosaccharides in the plasmatic membrane. Another phenotypic characteristic of malignant cells consists in the expression of high levels of intracellular glutathione (GSH). The aim of the present work was to demonstrate that the inhibition of N-glycosylation induces changes in intracellular GSH levels, and in turn participates in the inhibition of the metastatic potential of tumor cells by tunicamycin treatment. Firstly, we demonstrated that in comparison to the poorly metastatic cell line F21, the highly metastatic cells S4MH express a higher number of Asn-linked beta1-6 branched oligosaccharides and sialic acid (SA) and/or chitobiose oligosaccharides in glycoproteins involved in the regulation of the adhesion efficiency of tumor cells on endothelial cells and extracellular matrix. Our results showed that the decrease in S4MH cell adhesion efficiency on endothelial cells and extracellular matrix after the inhibition of N-glycan processing by tunicamycin treatment was caused by: (1) inhibition of the expression of N-glycan structures recognized by endothelial endogenous lectins, including beta1-6 branched oligosaccharides and SA and/or chitobiose oligosaccharides, and (2) redistribution of cell surface glycoproteins with beta1-6 branched oligosaccharides and/or SA and/or chitobiose oligosaccharides in their structures, caused by the depletion of intracellular GSH levels. The latter condition prevents the organization of these glycoproteins in the plasmatic membrane of S4MH cells necessary for anchoring to the substratum.
AuthorsY Calle, T Palomares, B Castro, M del Olmo, P Bilbao, A Alonso-Varona
JournalChemotherapy (Chemotherapy) 2000 Nov-Dec Vol. 46 Issue 6 Pg. 408-28 ISSN: 0009-3157 [Print] Switzerland
PMID11053907 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright 2000 S. Karger AG, Basel
Chemical References
  • Actins
  • Anti-Bacterial Agents
  • Antimetabolites, Antineoplastic
  • Disaccharides
  • Lectins
  • Ligands
  • Oligosaccharides
  • Polysaccharides
  • Tunicamycin
  • Buthionine Sulfoximine
  • chitobiose
  • Glutathione
  • N-Acetylneuraminic Acid
Topics
  • Actins (drug effects, ultrastructure)
  • Animals
  • Anti-Bacterial Agents (pharmacology)
  • Antimetabolites, Antineoplastic (pharmacology)
  • Buthionine Sulfoximine (pharmacology)
  • Carcinogenicity Tests
  • Cell Adhesion (drug effects)
  • Disaccharides (metabolism)
  • Extracellular Matrix (pathology)
  • Female
  • Glutathione (metabolism)
  • Glycosylation
  • Humans
  • Lectins (metabolism)
  • Ligands
  • Male
  • N-Acetylneuraminic Acid (metabolism)
  • Neoplasm Metastasis (pathology)
  • Oligosaccharides (chemistry, metabolism)
  • Polysaccharides (metabolism)
  • Rats
  • Rats, Wistar
  • Rhabdomyosarcoma (metabolism, pathology)
  • Tumor Cells, Cultured
  • Tunicamycin (pharmacology)

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