Characteristics of the inhibition of human promyelocytic leukaemia HL60 cell growth by S-D-lactoylglutathione in vitro.
The mechanism of the inhibition of proliferation of human leukaemia 60 (HL60) cells by S-D-lactoylglutathione in vitro was investigated. The median inhibitory concentration IC50 value was 66 microM (95% C.I. 50-87 microM; n = 18). The inhibition of leukaemia cell growth required exposure of HL60 cells to S-D-lactoylglutathione (and metabolites) for 12 h, with maximum growth inhibition achieved after 24 h. Removal and replacement of culture medium within the initial 12 h of culture prevented inhibition of growth and toxicity. S-D-lactoylglutathione was consumed within the initial 3 h of culture. Pretreatment of culture medium containing 10% foetal calf serum for 3 h produced no subsequent inhibition of HL60 cell growth. Incubation of HL60 cells in culture medium with low serum content (5% v/v) produced a decreased rate of cell proliferation and a decreased response to S-D-lactoylglutathione. S-D-lactoylglutathione inhibited uptake of 3H-thymidine into DNA in the third hour of culture where the median inhibitory concentration IC50 value was 74 microM (95% C.I. 51-102; n = 10). The mechanism of inhibition of HL60 cell growth by S-D-lactoylglutathione is unknown but may be cell cycle related, mediated by inhibition of DNA synthesis and involve an active metabolite which may be removed and/or inactivated by a change in culture medium.
Edwards
L
L
Department of Chemistry and Biological Chemistry, University of Essex, Colchester, U.K.
Clelland
J D
JD
Thornalley
P J
PJ
D002455:Cell Division / Q000187:drug effects; D003470:Culture Media; D005978:Glutathione / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects
D003470:Culture Media; D006131:Growth Inhibitors; D005978:Glutathione; C013585:S-lactoylglutathione