Inhibition of proliferation of human promyelocytic leukaemia HL60 cells by S-D-lactoylglutathione in vitro.
Human promyelocytic leukaemia HL60 cells were incubated with the glyoxalase intermediate S-D-lactoylglutathione in culture. The effects on cell proliferation, maturation, viability and cell cycle were investigated. When HL60 cells (5 x 10(4)/ml) were incubated with 50-500 microM S-D-lactoylglutathione for two days, the rate of cell proliferation was decreased. This effect was maximal at 500 microM S-D-lactoylglutathione where the cell proliferation rate was only 16% of control levels. There was a concomitant decrease in cell viability but little differentiation. During the first day of treatment, there was a significant decrease in the percentage of cells in the G2-M phase of the cell cycle with a concomitant increase in the G0-G1 phase. In contrast, when HL60 cells were incubated with 1.0-1.5 mM S-D-lactoylglutathione, the inhibition of cell proliferation was progressively lifted, with a concomitant increase in the percentage of differentiated cells (27% differentiation with 1.5 mM S-D-lactoylglutathione). The activities of glyoxalase II and gamma-glutamyl transpeptidase were increased in these cells. S-D-Lactoylglutathione slowly entered the HL60 cells and was consumed over the period when changes in cell cycle distribution, growth arrest and decrease in cell viability were observed. The mechanism of inhibition of proliferation of HL60 promyelocytes by S-D-lactoylglutathione is unknown but it may be related to the ability of S-D-lactoylglutathione to stimulate the assembly of microtubules.
Thornalley
P J
PJ
Pharmaceutical Sciences Institute, Aston University, Birmingham, U.K.
Tisdale
M J
MJ
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005978:Glutathione / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000494:pharmacology; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism / Q000473:pathology*; D013869:Thiolester Hydrolases / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005723:gamma-Glutamyltransferase / Q000494:pharmacology; D000099301:Hydroxyacylglutathione Hydrolase
D000970:Antineoplastic Agents; D005978:Glutathione; D006131:Growth Inhibitors; D007791:Lactoylglutathione Lyase; D013869:Thiolester Hydrolases; D005723:gamma-Glutamyltransferase; D000099301:Hydroxyacylglutathione Hydrolase; C013585:S-lactoylglutathione