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Increased membrane permeability for an antitumoral alkyl lysophospholipid in sensitive tumor cells

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Lipids

Abstract

We have investigated cellular sensitivity to the antitumoral alkyl lysophospholipid (ALP) 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3) in vitro. The permeation of this lipid into the cell was not influenced by metabolic inhibitors of ATP biosynthesis. ET-18-OCH3 uptake was not saturable within sublytic concentrations, but could be inhibited in part by cytochalasin B (CB) and dipyridamole. The activation energy of the CB-sensitive uptake process was increased up to threefold compared to CB-insensitive uptake. ET-18-OCH3 influx and equilibrium binding of ET-18-OCH3 were decreased in a fibrosarcoma cell variant (MethA) selected for ET-18-OCH3 resistance. The resistant MethA cells were also less sensitive to cytolysis by lysophosphatidylcholine and other ALP. After 72 hr, the resistant MethA cells had metabolized only 11.8% more of the absorbed ET-18-OCH3 than sensitive MethA cells. However, they tolerated at least a 30-fold concentration of this ALP. The uptake mechanism, which could be inhibited by CB, was less active in resistant MethA cells and several other ALP-resistant cell lines. The concentration of CB, required for maximal uptake inhibition, was increased more than four times in the ALP-sensitive tumor cell lines. CB-specific ET-18-OCH3 uptake was also enhanced after virus transformation of 3T3 fibroblasts by SV 40. Dipyridamole retarded the ET-18-OCH3-mediated cell destruction.

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Abbreviations

ALP:

alkyl lysophospholipids

2-LPC:

lysophosphatidylcholine (1-acyl-sn-glycero-3-phosphocholine)

ET-18-OCH3 :

1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine

D-ET-16-OH:

3-O-hexadecyl-sn-glycero-1-phosphocholine

L-ET-16-OH:

1-O-hexadecyl-sn-glycero-3-phosphocholine

CB:

cytochalasin B

CE:

cytochalasin E

DP:

dipyridamole

FBS:

fetal bovine serum

BSA:

bovine serum albumin

DMEM:

Dulbecco’s modified Eagle’s medium

DMSO:

dimethyl sulfoxide

MO:

macrophage

PBS:

phosphate-buffered saline

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Authors and Affiliations

  1. Max-Planck-Institut fuer Immunbiologie, Stuebeweg 51, 7800, Freiburg, Federal Republic of Germany

    Joachim Storch & Paul G. Munder

Authors
  1. Joachim Storch
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  2. Paul G. Munder
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Storch, J., Munder, P.G. Increased membrane permeability for an antitumoral alkyl lysophospholipid in sensitive tumor cells. Lipids 22, 813–819 (1987). https://doi.org/10.1007/BF02535536

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  • DOI: https://doi.org/10.1007/BF02535536

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