Effects of hexadecylphosphocholine on phosphatidylcholine and phosphatidylserine metabolism in human lymphoma cells.
Hexadecylphosphocholine (HePC) belongs to a new group of antineoplastic agents, the alkylphosphocholines (APC). HePC shows a broad spectrum of biological effects in various cells in vitro and in vivo. It has pronounced antiproliferative effects on neoplastic cells. The molecular mechanism by which HePC exerts its biological effects is still under investigation. By generating a HePC-resistant cell variant of the lymphoma cell line Raji, we established a model to investigate which molecular mechanism may be responsible for the antiproliferative action of HePC. Here we present data showing that HePC substantially interferes with the metabolism of cellular phosphatidylcholine (PC) and phosphatidylserine (PS) in the human lymphoma cell line Raji. HePC leads to an inhibition of PC synthesis via CDP-choline and as a compensatory mechanism enhances the generation of PC via PS indicating that the reduced PC synthesis seems to significantly disturb cellular homeostasis. In HePC-resistant Raji cells, PC synthesis via CDP-choline is constitutively less active and is not further reduced by HePC. Resistant Raji cells do not seem to use the alternative pathway of PC synthesis via PS nor can this be induced by HePC. The resistance mechanism may therefore be independent of cell membrane metabolism.
Berkovic
Dinko
D
Department of Internal Medicine, University Clinic of Göttingen, Göttingen, Germany. berkovic@gmx.de
Sievers
Sabine
S
Haase
Detlef
D
Fleer
Eduard A M
EA
Binder
Claudia
C
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002794:Choline / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008223:Lymphoma / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism*; D010718:Phosphatidylserines / Q000378:metabolism*; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D012694:Serine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; D010767:Phosphorylcholine; D012694:Serine; C039128:miltefosine; D002794:Choline