The phospholipid analogue, hexadecylphosphocholine, inhibits protein kinase C in vitro and antagonises phorbol ester-stimulated cell proliferation.
The antineoplastic agent, hexadecylphosphocholine, a phospholipid analogue, inhibited phosphatidylserine-activated protein kinase C in vitro at concentrations higher than 40 mumol/l. The half-inhibitory concentration (IC50) was 62 mumol/l. Another alkylphosphocholine, dodecylphosphocholine, did not have an inhibitory effect on protein kinase C. At the same concentrations, hexadecylphosphocholine antagonised the phorbol ester-stimulated proliferation of Madin-Darby canine kidney cells whereas dodecylphosphocholine had no effect. In addition, phorbol ester-induced morphological changes of these epithelial cells were antagonised by hexadecylphosphocholine. Both effects of hexadecylphosphocholine, the inhibition of protein kinase C and the antagonisation of the altered cell morphology induced by phorbol ester, were comparable to those observed after treatment with sphingosine, a known protein kinase C inhibitor. We conclude that one possible mechanism of the antineoplastic action of hexadecylphosphocholine is mediated by inhibition of protein kinase C.
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Institut für Molekularbiologie und Biochemie, Freien Universität Berlin, Dahlem, Germany.
Haase
R
R
Buchner
K
K
Wieder
T
T
Hucho
F
F
Reutter
W
W
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002478:Cells, Cultured; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D008938:Mitosis / Q000187:drug effects; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D013755:Tetradecanoylphorbol Acetate
D000970:Antineoplastic Agents; D010767:Phosphorylcholine; C039128:miltefosine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate