van Blitterswijk W J, van der Bend R L, Kramer I M, Verhoeven A J, Hilkmann H, de Widt J
Division of Cell Biology, The Netherlands Cancer Institute (Antoni van Leeuwenhoek-Huis), Amsterdam.
Lipids. 1987 Nov;22(11):842-6. doi: 10.1007/BF02535541.
In our search for the mechanisms by which the drug 1-O-alkyl-2-O-methylglycero-3-phosphocholine (AMG-PC) inhibits tumor growth and metastasis, we have detected a metabolite, 1-O-alkyl-2-O-methylglycerol (AMG), in membranes of MO4 mouse fibrosarcoma cells grown in the presence of the drug. Synthetic AMG inhibited the activation of highly purified human protein kinase C by diacylglycerol in the presence of phosphatidylserine. Furthermore, AMG also inhibited the receptor-specific binding of 3H-phorbol-12,13-dibutyrate to human HL-60 promyeloid leukemia cells in a dose-dependent fashion. AMG-PC was not effective or much less so in these assays. We suggest that interaction of the metabolite AMG with protein kinase C may inhibit stimulus-response coupling in tumor cells and may thus potentially contribute to the mechanism by which AMG-PC exerts its anticancer activities.
在探寻药物1-O-烷基-2-O-甲基甘油-3-磷酸胆碱（AMG-PC）抑制肿瘤生长和转移的机制过程中，我们在存在该药物的条件下培养的MO4小鼠纤维肉瘤细胞膜中检测到一种代谢产物1-O-烷基-2-O-甲基甘油（AMG）。合成的AMG在磷脂酰丝氨酸存在的情况下，抑制了二酰基甘油对高度纯化的人蛋白激酶C的激活作用。此外，AMG还以剂量依赖的方式抑制了3H-佛波醇-12,13-二丁酸酯与人HL-60早幼粒细胞白血病细胞的受体特异性结合。在这些实验中，AMG-PC没有效果或效果要小得多。我们认为，代谢产物AMG与蛋白激酶C的相互作用可能会抑制肿瘤细胞中的刺激-反应偶联，因此可能潜在地有助于AMG-PC发挥其抗癌活性的机制。
