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Interaction of 10-(octyloxy) decyl-2-(trimethylammonium) ethyl phosphate with mimetic membranes and cytotoxic effect on leukemic cells
Ist Teil von
Biochimica et biophysica acta, 2010-09, Vol.1798 (9), p.1714-1723
Ort / Verlag
Netherlands: Elsevier B.V
Erscheinungsjahr
2010
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
10-(Octyloxy) decyl-2-(trimethylammonium) ethyl phosphate (ODPC) is an alkylphospholipid that can interact with cell membranes because of its amphiphilic character. We describe here the interaction of ODPC with liposomes and its toxicity to leukemic cells with an ED-50 of 5.4, 5.6 and 2.9
μM for 72
h of treatment for inhibition of proliferation of NB4, U937 and K562 cell lines, respectively, and lack of toxicity to normal hematopoietic progenitor cells at concentrations up to 25
μM. The ED-50 for the non-malignant HEK-293 and primary human umbilical vein endothelial cells (HUVEC) was 63.4 and 60.7
μM, respectively. The critical micellar concentration (CMC) of ODPC was 200
μM. Dynamic light scattering indicated that dipalmitoylphosphatidylcholine (DPPC) liposome size was affected only above the CMC of ODPC. Differential calorimetric scanning (DCS) of liposomes indicated a critical transition temperature (
T
c) of 41.5
°C and an enthalpy (∆H) variation of 7.3
kcal mol
−
1. The presence of 25
μM ODPC decreased
T
c and ∆H to 39.3
°C and 4.7
kcal mol
−
1, respectively. ODPC at 250
μM destabilized the liposomes (36.3
°C, 0.46
kcal mol
−
1). Kinetics of 5(6)-carboxyfluorescein (CF) leakage from different liposome systems indicated that the rate and extent of CF release depended on liposome composition and ODPC concentration and that above the CMC it was instantaneous. Overall, the data indicate that ODPC acts on in vitro membrane systems and leukemia cell lines at concentrations below its CMC, suggesting that it does not act as a detergent and that this effect is dependent on membrane composition.