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

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.

• Authors: J Storch, P G Munder
• Journal: Lipids (Lipids) Vol. 22 Issue 11 Pg. 813-9 (Nov 1987) ISSN: 0024-4201 [Print] United States
• PMID: 3444371 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Cytotoxins
• Glyceryl Ethers
• Lysophospholipids
• Phospholipid Ethers
• edelfosine
• Cytochalasin B
• Dipyridamole

Topics

• Animals
• Antineoplastic Agents (pharmacokinetics, pharmacology)
• Cell Line
• Cell Membrane Permeability (drug effects)
• Cytochalasin B (pharmacology)
• Cytotoxins (pharmacokinetics, pharmacology)
• Dipyridamole (pharmacology)
• Glyceryl Ethers (pharmacokinetics, pharmacology)
• Lysophospholipids (pharmacokinetics, pharmacology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Phospholipid Ethers (pharmacokinetics, pharmacology)
• Tumor Cells, Cultured (drug effects)