BENZYL-N-ACETYL-ALPHA-D-GALACTOSAMINIDE INHIBITS THE SIALYLATION AND THE SECRETION OF MUCINS BY A MUCIN SECRETING HT-29 CELL SUBPOPULATION

We have analysed the mucins synthesized by the HT-29 MTX cell subpopul ation, derived from the HT-29 human colon carcinoma cells through a se lective pressure with methotrexate (Lesuffleur et al., 1990, Cancer Re s 50: 6334-43), in the presence of benzyl-N-acetyl-alpha-galactosamini de (GalNAc alpha-O-benzyl), which is a potential competitive inhibitor of the beta 1,3-galactosyltransferase that synthesizes the T-antigen. The main observation was a 13-fold decrease in the sialic acid conten t of mucins after 24 h of exposure to 5 mM GalNAc alpha-O-benzyl. This effect was accompanied by an increased reactivity of these mucins to peanut lectin, testifying to the higher amount of T-antigen. The secon d observation was a decrease in the secretion of the mucins by GalNAc alpha-O-benzyl treated cells. The decrease in mucin sialylation was ac hieved through the in situ beta-galactosylation of GalNAc alpha-O-benz yl into Gal beta 1-3GalNAc alpha-O-benzyl, which acts as a competitive substrate of Gal beta 1-3GalNAc alpha 2,3-sialyltransferase, as shown by the intracellular accumulation of NeuAc alpha 2-3Gal beta 1-3GalNA c alpha-O-benzyl in treated cells.