Effects of hexadecylphosphocholine on membrane phospholipid metabolism in human tumour cells.
Hexadecylphosphocholine (HePC) is an analogue of the antiproliferative alkyllysophospholipids (ALP). As these lipid-like compounds interfere with membrane lipid metabolism at several sites, we studied the effects of HePC on uptake and metabolism of inositol and choline, two important phospholipid precursor molecules in two sensitive cell lines, Raji and KB, and in a resistant variant of KB cells, KBr. HePC substantially inhibited the membrane uptake of inositol and of choline in KB and Raji. Inositol uptake of KBr cells was constitutively low and was not further decreased by HePC. In all three cell lines, uptake inhibition of choline was less pronounced. Uptake inhibition showed characteristics of a non-specific effect, probably due to the physicochemical properties of HePC as a "lyso" structure. Decreased uptake of inositol did not affect phosphoinositide synthesis. Cellular phosphatidylcholine (PC) metabolism seemed to be affected through inhibition of choline incorporation and enhancement of PC degradation in the two sensitive cells. In KBr cells, these effects were not observed.
Berkovic
D
D
University Clinic of Göttingen, Department of Internal Medicine, Germany.
Grunwald
U
U
Menzel
W
W
Unger
C
C
Hiddemann
W
W
Fleer
E A
EA
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007294:Inositol / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism
D000970:Antineoplastic Agents; D010743:Phospholipids; D010767:Phosphorylcholine; D007294:Inositol; C039128:miltefosine; D002794:Choline