Investigations on the cellular uptake of hexadecylphosphocholine.
The uptake of [(9,10)-3H]hexadecylphosphocholine (HePC) in six tumor cell lines was studied. All cell lines incorporated HePC in similar amounts, with the exception of the epidermoid cancer cell line KB, which took up higher amounts of HePC. The uptake of HePC at 37 degrees C was shown to be time and concentration dependent. At 20 degrees C, uptake was drastically reduced and at 4 degrees C it was blocked completely. Binding of HePC, at 4 degrees C, was not saturable at concentrations between 5 micrograms/mL (11.8 microM) and 100 micrograms/mL (235.3 microM), indicating that cell surface binding is not receptor-mediated. Furthermore, the effects of inhibitors of endocytosis were investigated. We observed a pronounced inhibitory effect by monensin and cytochalasin B. Colchicine was somewhat less effective whereas chloroquine was almost without effect. From these data we conclude that uptake of HePC is most probably mediated via a receptor-independent endocytotic mechanism.
Department of Hematology and Oncology, University Clinic of Goettingen, Germany.
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Fleer
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Berkovic
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Eibl
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Unger
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D001693:Biological Transport, Active / Q000187:drug effects; D003571:Cytochalasin B / Q000494:pharmacology; D004705:Endocytosis; D006801:Humans; D007700:Kinetics; D050356:Lipid Metabolism; D008566:Membranes / Q000378:metabolism; D051379:Mice; D008985:Monensin / Q000494:pharmacology; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D013696:Temperature; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D010767:Phosphorylcholine; D003571:Cytochalasin B; C039128:miltefosine; D008985:Monensin