Influence of platelet-activating factor, lyso-platelet-activating factor and edelfosine on Langmuir monolayers imitating plasma membranes of cell lines differing in susceptibility to anti-cancer treatment: the effect of plasmalogen level.
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.
Faculty of Chemistry, Department of Environmental Chemistry, Jagiellonian University, , Gronostajowa 3, 30-387 Kraków, Poland.
Michał
M
Flasiński
Katarzyna
K
Hąc-Wydro
Paweł
P
Wydro
Patrycja
P
Dynarowicz-Łątka
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D008567:Membranes, Artificial; D009369:Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000378:metabolism; D010742:Phospholipid Ethers / Q000737:chemistry / Q000494:pharmacology*; D010955:Plasmalogens / Q000737:chemistry / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D008567:Membranes, Artificial; C029271:O-deacetyl platelet activating factor; D010742:Phospholipid Ethers; D010955:Plasmalogens; D010972:Platelet Activating Factor; C026659:edelfosine
Brewster angle microscopy; Langmuir monolayers; plasmalogens; single-chained ether lipids