Flasiński Michał, Hąc-Wydro Katarzyna, Wydro Paweł, Dynarowicz-Łątka Patrycja
Faculty of Chemistry, Department of Environmental Chemistry, Jagiellonian University, , Gronostajowa 3, 30-387 Kraków, Poland.
J R Soc Interface. 2014 Apr 2;11(95):20131103. doi: 10.1098/rsif.2013.1103. Print 2014 Jun 6.
Three structurally related but differing in biological activities single-chained ether phospholipids (PAF (platelet-activating factor) and lyso-PAF) and an anti-cancer drug (edelfosine (ED)) were investigated in Langmuir monolayers imitating natural membranes. The aim of the undertaken experiments was to study the influence of these lipids on monolayers mimicking plasma membranes of cell lines differing in susceptibility to the anti-cancer activity of ED, i.e. promyelocytic leukaemia cells (HL-60) and promyeloblastic leukaemia cells (K-562). As these cells differ essentially in the cholesterol/phospholipid ratio and plasmalogen concentration in the membrane, we have carried out systematic investigations in artificial systems of various compositions. The results for model leukaemia cell membrane were compared with data acquired for systems imitating normal leucocytes. Our results show that the level of plasmalogens significantly modulates the influence of the single-chained phospholipids on the investigated systems. The experiments confirmed also that the interactions of ether lipids with a model membrane of HL-60 cells (in biological tests sensitive to ED) have opposite character when compared with K-562, being resistant to ED. Moreover, the values of the parameters characterizing monolayers serving as membrane models (strength of interactions, monolayers fluidity and morphology) proved both sensitivity of these cells to ED and lack of their susceptibility towards PAF. Interestingly, it has been found that lyso-PAF, which is usually described as an inactive precursor of PAF, displays a stronger effect on HL-60 model membranes than ED.
研究了三种结构相关但生物活性不同的单链醚磷脂（血小板活化因子（PAF）和溶血PAF）以及一种抗癌药物（依地福新（ED））在模拟天然膜的朗缪尔单层中的情况。所进行实验的目的是研究这些脂质对模拟不同细胞系质膜的单层的影响，这些细胞系对ED的抗癌活性敏感性不同，即早幼粒细胞白血病细胞（HL - 60）和早幼粒细胞白血病细胞（K - 562）。由于这些细胞在膜中的胆固醇/磷脂比率和缩醛磷脂浓度上存在本质差异，我们在各种组成的人工系统中进行了系统研究。将模型白血病细胞膜的结果与模拟正常白细胞的系统所获得的数据进行了比较。我们的结果表明，缩醛磷脂的水平显著调节了单链磷脂对所研究系统的影响。实验还证实，与对ED有抗性的K - 562相比，醚脂质与HL - 60细胞模型膜（在生物学测试中对ED敏感）的相互作用具有相反的特性。此外，表征用作膜模型的单层的参数值（相互作用强度、单层流动性和形态）证明了这些细胞对ED的敏感性以及它们对PAF的不敏感性。有趣的是，已发现通常被描述为PAF无活性前体的溶血PAF对HL - 60模型膜的作用比ED更强。
