Christoph C. Geilen , Rüdiger Haase , Klaus Buchner , Thomas Wieder , Ferdinand Hucho , Werner Reutter
{"title":"The phospholipid analogue, hexadecylphosphocholine, inhibits protein kinase C in vitro and antagonises phorbol ester-stimulated cell proliferation","authors":"Christoph C. Geilen , Rüdiger Haase , Klaus Buchner , Thomas Wieder , Ferdinand Hucho , Werner Reutter","doi":"10.1016/0277-5379(91)90438-J","DOIUrl":null,"url":null,"abstract":"<div><p>The antineoplastic agent, hexadecylphosphocholine, a phospholipid analogue, inhibited phosphatidylserine-activated protein kinase C <em>in vitro</em> at concentrations higher than 40 μmol/l. The half-inhibitory concentration (IC<sub>50</sub>) was 62 μmol/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 antineoplatic action of hexadecylphosphocholine is mediated by inhibition of protein kinase C.</p></div>","PeriodicalId":11925,"journal":{"name":"European Journal of Cancer and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"1991-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0277-5379(91)90438-J","citationCount":"60","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Cancer and Clinical Oncology","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/027753799190438J","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 60
Abstract
The antineoplastic agent, hexadecylphosphocholine, a phospholipid analogue, inhibited phosphatidylserine-activated protein kinase C in vitro at concentrations higher than 40 μmol/l. The half-inhibitory concentration (IC50) was 62 μmol/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 antineoplatic action of hexadecylphosphocholine is mediated by inhibition of protein kinase C.