Hofmann J, Ueberall F, Posch L, Maly K, Herrmann D B, Grunicke H
Institut für Medizinische Chemie, University of Innsbruck, Austria.
Lipids. 1989 Apr;24(4):312-7. doi: 10.1007/BF02535169.
The new phospholipid analogue 3-hexadecylmercapto-2-methoxy-methyl-propyl-1-phosphocholine inhibits the phospholipid-calcium-dependent protein kinase, partially purified from Walker carcinoma cells with a Ki value of 0.56 microM. The compound inhibits the phorbol ester stimulated phosphorylation of the ribosomal protein S6 indicating that the depression of Ca2+-phospholipid-dependent protein kinase by the alkyl phospholipid also occurs in intact cells. The dose effect curve for the inhibition of cell proliferation by 3-hexadecylmercapto-2-methoxy-methyl-propyl-1-phosphocholine in Walker cells exhibits a close correlation to the dose effect curve for the depression of Ca2+-phospholipid-dependent protein kinase activity. Although alternative mechanisms cannot be excluded, the data suggest that the growth inhibitory activity of 3-hexadecylmercapto-2-methoxy-methyl-propyl-1-phosphocholine correlates with the inhibition of Ca2+-phospholipid-dependent protein kinase. The antiproliferative activity of 3-hexadecylmercapto-2-methoxy-methyl-propyl-1-phosphocholine is synergistically enhanced by cis-diamminedichloroplatinum(II).
新型磷脂类似物3-十六烷基巯基-2-甲氧基甲基丙基-1-磷酸胆碱可抑制从Walker癌细胞中部分纯化得到的磷脂钙依赖性蛋白激酶，其抑制常数（Ki）值为0.56微摩尔。该化合物抑制佛波酯刺激的核糖体蛋白S6磷酸化，表明烷基磷脂对Ca2+磷脂依赖性蛋白激酶的抑制作用在完整细胞中也会发生。3-十六烷基巯基-2-甲氧基甲基丙基-1-磷酸胆碱对Walker细胞增殖抑制的剂量效应曲线与Ca2+磷脂依赖性蛋白激酶活性降低的剂量效应曲线密切相关。尽管不能排除其他机制，但数据表明3-十六烷基巯基-2-甲氧基甲基丙基-1-磷酸胆碱的生长抑制活性与Ca2+磷脂依赖性蛋白激酶的抑制作用相关。顺式二氯二氨铂（II）可协同增强3-十六烷基巯基-2-甲氧基甲基丙基-1-磷酸胆碱的抗增殖活性。
