Inhibition of mucin glycosylation by aryl-N-acetyl-alpha-galactosaminides in human colon cancer cells.
Specific inhibitors of the glycosylation of O-glycosidically linked glycoproteins have not previously been described. When tested for their effects on mucin glycosylation in a mucin-producing colon cancer cell line, LS174T, benzyl-, phenyl-, and p-nitrophenyl-N-acetyl-alpha-galactosaminide inhibited the formation of fully glycosylated mucin in a dose-dependent manner. Free aryl-oligosaccharides were found in the medium of treated cells labeled with [3H]glucosamine, [3H]galactose, [3H]fucose, [3H]mannosamine, or phenyl-alpha-[6-3H] N-acetylgalactosamine. UDP-Gal:GalNAc-beta 1,3-galactosyltransferase was inhibited by aryl-N-acetyl-alpha-galactosaminides but not by a number of other aryl-glycosides. Treatment with these inhibitors also causes reversible morphologic changes including formation of intercellular cysts. Aryl-N-acetyl-alpha-galactosaminides can be useful for the structural and functional studies of mucin macromolecules and other O-linked glycoproteins.
Kuan
S F
SF
Gastrointestinal Research Laboratory, Veterans Administration Medical Center, San Francisco, California 94121.
Byrd
J C
JC
Basbaum
C
C
Kim
Y S
YS
D000116:Acetylgalactosamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002460:Cell Line; D002850:Chromatography, Gel; D003110:Colonic Neoplasms / Q000378:metabolism*; D005688:Galactosamine; D005944:Glucosamine / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D008358:Mannose / Q000378:metabolism; D008854:Microscopy, Electron; D009077:Mucins / Q000378:metabolism*; D009844:Oligosaccharides / Q000302:isolation & purification; D015388:Organelles / Q000187:drug effects / Q000648:ultrastructure; D013329:Structure-Activity Relationship; D013912:Threonine / Q000378:metabolism; D014316:Tritium; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D009077:Mucins; D009844:Oligosaccharides; D014316:Tritium; D013912:Threonine; D005688:Galactosamine; D000116:Acetylgalactosamine; D005944:Glucosamine; D008358:Mannose