Inhibition of growth of human leukaemia 60 cells by S-2-hydroxyacylglutathiones and monoethyl ester derivatives.
S-2-Hydroxyacylglutathione derivatives were found to induce growth arrest and toxicity in human leukaemia 60 cells in culture. S-D-Lactoylglutathione was the most effective with a median inhibitory concentration IC50 of 82 microM (95% C.I. 65-105 microM). No similar toxicity was induced by reduced glutathione and/or the corresponding aldonic acid (500 microM) in human leukaemia 60 cells, nor by S-D-lactoylglutathione (500 microM) in mature human neutrophils under the same culture conditions. Monoethyl ester derivatives of the S-2-hydroxyacylglutathiones were prepared and also induced growth arrest and toxicity but were less effective than the corresponding unesterified compounds. S-2-Hydroxyacylglutathione derivatives also inhibited the incorporation of [3H]thymidine into DNA early in the development of toxicity: for S-D-lactoylglutathione, the median inhibitory concentration was 74 microM (95% C.I. 47-116 microM). The mechanism of the inhibition of human leukaemia cell growth by S-D-lactoylglutathione and other S-2-hydroxyacylglutathione derivatives is unknown but appears to be mediated by the inhibition of DNA synthesis.
Clelland
J D
JD
Department of Chemistry and Biological Chemistry, University of Essex, Colchester, U.K.
Allen
R E
RE
Thornalley
P J
PJ
D002455:Cell Division / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D004273:DNA, Neoplasm / Q000378:metabolism; D004952:Esters / Q000737:chemistry / Q000494:pharmacology; D005978:Glutathione / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D009504:Neutrophils / Q000187:drug effects; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000473:pathology
D004273:DNA, Neoplasm; D004952:Esters; D005978:Glutathione; C013585:S-lactoylglutathione; D013936:Thymidine