L. Edwards et al., CHARACTERISTICS OF THE INHIBITION OF HUMAN PROMYELOCYTIC LEUKEMIA HL-60 CELL-GROWTH BY S-D-LACTOYLGLUTATHIONE INVITRO, Leukemia research, 17(4), 1993, pp. 305-310
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 muM (95% C.I. 50-87
muM; n = 18). The inhibition of leukaemia cell growth required exposu
re of HL60 cells to S-D-lactoylglutathione (and metabolites) for 12 h,
with maximum growth inhibition achieved after 24 h. Removal and repla
cement 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 con
taining 10% foetal calf serum for 3 h produced no subsequent inhibitio
n of HL60 cell growth. Incubation of HL60 cells in culture medium with
low serum content (5% v/v) produced a decreased rate of cell prolifer
ation and a decreased response to S-D-lactoylglutathione. S-D-lactoylg
lutathione inhibited uptake of H-3-thymidine into DNA in the third hou
r of culture where the median inhibitory concentration IC50 value, was
74 muM (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 cycl
e related, mediated by inhibition of DNA synthesis and involve an acti
ve metabolite which may be removed and/or inactivated by a change in c
ulture medium.