The phospholipid analogue, hexadecylphosphocholine, inhibits protein kinase C in vitro and antagonises phorbol ester-stimulated cell proliferation

Christoph C. Geilen , Rüdiger Haase , Klaus Buchner , Thomas Wieder , Ferdinand Hucho , Werner Reutter
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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.

磷脂类似物,十六烷基磷脂胆碱,在体外抑制蛋白激酶C和拮抗酚酯刺激的细胞增殖
抗肿瘤药物,磷脂类似物十六烷基磷脂胆碱,在体外浓度高于40 μmol/l时抑制磷脂酰丝氨酸活化的蛋白激酶C。半抑制浓度(IC50)为62 μmol/l。另一种烷基磷胆碱,十二烷基磷胆碱,对蛋白激酶c没有抑制作用。在相同浓度下,十六烷基磷胆碱可以拮抗酚酯刺激的Madin-Darby犬肾细胞增殖,而十二烷基磷胆碱则没有作用。此外,磷酯诱导的上皮细胞形态变化可被十六烷基磷胆碱拮抗。十六烷基磷酸胆碱对蛋白激酶C的抑制作用和对phorbol酯诱导的细胞形态改变的拮抗作用与用鞘氨醇(一种已知的蛋白激酶C抑制剂)治疗后观察到的效果相当。我们认为,十六烷基磷脂胆碱抗肿瘤作用的一个可能机制是通过抑制蛋白激酶C介导的。
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