Thornalley P J, Tisdale M J
Pharmaceutical Sciences Institute, Aston University, Birmingham, U.K.
Leuk Res. 1988;12(11-12):897-904. doi: 10.1016/0145-2126(88)90016-1.
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.
人早幼粒细胞白血病HL60细胞在培养过程中与乙二醛酶中间体S-D-乳酰谷胱甘肽一起孵育。研究了其对细胞增殖、成熟、活力和细胞周期的影响。当HL60细胞（5×10⁴/ml）与50 - 500μM的S-D-乳酰谷胱甘肽孵育两天时，细胞增殖速率降低。在500μM S-D-乳酰谷胱甘肽时这种作用最大，此时细胞增殖速率仅为对照水平的16%。细胞活力随之下降，但分化很少。在处理的第一天，细胞周期G2-M期的细胞百分比显著下降，同时G0-G1期增加。相反，当HL60细胞与1.0 - 1.5 mM的S-D-乳酰谷胱甘肽孵育时，细胞增殖的抑制作用逐渐解除，同时分化细胞的百分比增加（1.5 mM S-D-乳酰谷胱甘肽时27%分化）。这些细胞中乙二醛酶II和γ-谷氨酰转肽酶的活性增加。S-D-乳酰谷胱甘肽缓慢进入HL60细胞，并在观察到细胞周期分布变化、生长停滞和细胞活力下降的期间被消耗。S-D-乳酰谷胱甘肽抑制HL60早幼粒细胞增殖的机制尚不清楚，但可能与S-D-乳酰谷胱甘肽刺激微管组装的能力有关。
