尿苷对S-D-乳酰谷胱甘肽诱导的人白血病60细胞生长抑制的预防作用

Prevention of S-D-lactoylglutathione-induced inhibition of human leukaemia 60 cell growth by uridine.

作者信息

Edwards L G, Thornalley P J

机构信息

Department of Chemistry and Biological Chemistry, University of Essex, Colchester, U.K.

出版信息

Leuk Res. 1994 Sep;18(9):717-22. doi: 10.1016/0145-2126(94)90072-8.

DOI:10.1016/0145-2126(94)90072-8

PMID:7934147

Abstract

The anti-proliferative activity of S-D-lactoylglutathione is of interest since it has a low toxicity to differentiated and non-malignant proliferating tissues, and its mechanism of action appears to be dissimilar to other anti-proliferative agents. Addition of uridine completely and addition of cytidine partially prevented S-D-lactoylglutathione-induced growth inhibition of human leukaemia 60 (HL60) cells in vitro. Other nucleosides had no significant effect. The concentrations of UTP, CTP, UDP and also ATP, ADP, GTP and GDP decreased in S-D-lactoylglutathione-treated HL60 cells, whereas the concentration of UDP-N-acetylhexosamine (UDP-N-acetyl-glucosamine + N-acetyl-galactosamine) increased, prior to cell death. This suggests that the anti-proliferative effects of S-D-lactoylglutathione are mediated by inhibition of uridylate synthesis.

摘要

S-D-乳酰谷胱甘肽的抗增殖活性备受关注，因为它对分化的和非恶性增殖组织毒性较低，且其作用机制似乎与其他抗增殖剂不同。添加尿苷可完全消除，而添加胞苷可部分防止S-D-乳酰谷胱甘肽在体外对人白血病60（HL60）细胞的生长抑制作用。其他核苷则无显著影响。在S-D-乳酰谷胱甘肽处理的HL60细胞中，UTP、CTP、UDP以及ATP、ADP、GTP和GDP的浓度降低，而在细胞死亡前，UDP-N-乙酰己糖胺（UDP-N-乙酰葡糖胺+N-乙酰半乳糖胺）的浓度升高。这表明S-D-乳酰谷胱甘肽的抗增殖作用是通过抑制尿苷酸合成介导的。