Prevention of S-D-lactoylglutathione-induced inhibition of human leukaemia 60 cell growth by uridine.
The anti-proliferative activity of S-D-lactoylglutathione is of interest since it has a low toxicity to differentiated and non-malignant proliferating tissues, and its mechanism of action appears to be dissimilar to other anti-proliferative agents. Addition of uridine completely and addition of cytidine partially prevented S-D-lactoylglutathione-induced growth inhibition of human leukaemia 60 (HL60) cells in vitro. Other nucleosides had no significant effect. The concentrations of UTP, CTP, UDP and also ATP, ADP, GTP and GDP decreased in S-D-lactoylglutathione-treated HL60 cells, whereas the concentration of UDP-N-acetylhexosamine (UDP-N-acetyl-glucosamine + N-acetyl-galactosamine) increased, prior to cell death. This suggests that the anti-proliferative effects of S-D-lactoylglutathione are mediated by inhibition of uridylate synthesis.
Edwards
L G
LG
Department of Chemistry and Biological Chemistry, University of Essex, Colchester, U.K.
Thornalley
P J
PJ
D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D003562:Cytidine / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006131:Growth Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D015473:Leukemia, Promyelocytic, Acute; D012265:Ribonucleotides / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014529:Uridine / Q000494:pharmacology*
D006131:Growth Inhibitors; D012265:Ribonucleotides; D003562:Cytidine; D005978:Glutathione; C013585:S-lactoylglutathione; D014529:Uridine