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

Author(s):Show less -

dos Santos, G. A. ^{[1, 2]} ; Thome, C. H. ^{[1, 3]} ; Ferreira, G. A. ^{[1, 4]} ; Yoneda, J. S. ^[5] ; Nobre, T. M. ^[6] ; Daghastanli, K. R. P. ^[7] ; Scheucher, P. S. ^{[1, 2]} ; Gimenes-Teixeira, H. L. ^{[1, 2]} ; Constantino, M. G. ^[5] ; de Oliveira, K. T. ^[8] ; Faca, V. M. ^[1] ; Falcao, R. P. ^{[1, 2]} ; Greene, L. J. ^{[1, 3, 4]} ; Rego, E. M. ^{[1, 2]} ; Ciancaglini, P. ^[5]

Affiliation

^[1] Inst Nacl Ciencia & Tecnol Celulas Tronco & Terap, Sao Paulo - Brazil

^[2] USP, Fac Med Ribeirao Preto, Dept Clin Med, BR-14051140 Ribeirao Preto, SP - Brazil

^[3] Univ Fed Sao Paulo, Escola Paulista Med, Dept Bioquim, BR-04039002 Sao Paulo - Brazil

^[4] USP, Fac Med Ribeirao Preto, Dept Biol Celular & Mol & Bioagentes Patogen, BR-14051140 Ribeirao Preto, SP - Brazil

^[5] USP, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Quim, BR-14040901 Ribeirao Preto, SP - Brazil

^[6] USP, Inst Fis Sao Carlos, BR-13560970 Sao Carlos, SP - Brazil

^[7] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-05508900 Sao Paulo - Brazil

^[8] Univ Fed Sao Carlos, Dept Quim, BR-13565905 Sao Carlos, SP - Brazil

• Document type: Journal article
• Source: BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES; v. 1798, n. 9, p. 1714-1723, SEP 2010.
• Web of Science Citations: 7

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. (AU)

• FAPESP's process: 08/06619-4 - Synthesis of new photosensitizers with potential aplication in photodynamic therapy
• Grantee: Kleber Thiago de Oliveira
• Support type: Research Grants - Young Investigators Grants