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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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