Interaction of 10-(octyloxy) decyl-2-(trimethylammonium) ethyl phosphate with mimetic membranes and cytotoxic effect on leukemic cells

Interaction of 10-(octyloxy) decyl-2-(trimethylammonium) ethyl phosphate with mimetic membranes and cytotoxic effect on leukemic cells

Author Santos, G. A. dos Google Scholar
Thomé, Carolina Hassibe Autor UNIFESP Google Scholar
Ferreira, Germano A Google Scholar
Yoneda, Juliana Sakamoto Google Scholar
Nobre, Thatyane Morimoto Google Scholar
Perez, Katia Regina Autor UNIFESP Google Scholar
Scheucher, Priscila Santos Google Scholar
Gimenes-Teixeira, Hamilton Luiz Google Scholar
Constantino, Maurício Gomes Google Scholar
Oliveira, Kleber Thiago de Google Scholar
Faça, Vítor Marcel Google Scholar
Falcão, Roberto Passetto Google Scholar
Greene, Lewis Joel Autor UNIFESP Google Scholar
Rego, Eduardo Magalhães Google Scholar
Ciancaglini, Pietro Google Scholar
Institution Universidade de São Paulo (USP)
Inst Nacl Ciencia & Tecnol Celulas Tronco & Terap
Universidade Federal de São Paulo (UNIFESP)
Universidade Federal de São Carlos (UFSCar)
Abstract 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 pM 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 pM. the ED-50 for the non-malignant HEK-293 and primary human umbilical vein endothelial cells (HUVEC) was 63.4 and 60.7 mu M, respectively. the critical micellar concentration (CMC) of ODPC was 200 mu M. 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 degrees C and an enthalpy (Delta H) variation of 7.3 kcal mol(-1). the presence of 25 mu M ODPC decreased T(c) and Delta H to 393 degrees C and 4.7 kcal mol(-1), respectively. ODPC at 250 mu M destabilized the liposomes (36.3 degrees 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. (C) 2010 Elsevier B.V. All rights reserved.
Keywords 10-(Octyloxy) decyl-2-(trimethylammonium)
ethyl phosphate
Language English
Sponsor Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Fundacao de Apoio ao Ensino
Pesquisa e Assistencia do Hospital das Clinicas da FMRP-USP (FAEPA)
Grant number FAPESP: 2008/06619-4
Date 2010-09-01
Published in Biochimica Et Biophysica Acta-biomembranes. Amsterdam: Elsevier B.V., v. 1798, n. 9, p. 1714-1723, 2010.
ISSN 0005-2736 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 1714-1723
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000280752100009

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