A metabolite of an antineoplastic ether phospholipid may inhibit transmembrane signalling via protein kinase C
- 1 November 1987
- Vol. 22 (11), 842-846
- https://doi.org/10.1007/bf02535541
Abstract
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 of3H-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.Keywords
This publication has 20 references indexed in Scilit:
- Accumulation of an alkyl lysophospholipid in tumor cell membranes affects membrane fluidity and tumor cell invasionLipids, 1987
- Stereospecificity of diacylglycerol for stimulus-response coupling in plateletsBiochemical and Biophysical Research Communications, 1986
- Polyclonal antibodies to phospholipid/Ca2+-dependent protein kinase and immunocytochemical localization of the enzyme in rat brain.Proceedings of the National Academy of Sciences, 1985
- Diacylglycerols mimic phorbol diester induction of leukemic cell differentiation.Proceedings of the National Academy of Sciences, 1985
- [31] Calcium-activated, phospholipid-dependent protein kinase (protein kinase C) from rat brainMethods in Enzymology, 1983
- Receptor-mediated Modulation of Human Monocyte, Neutrophil, Lymphocyte, and Platelet Function by Phorbol DiestersJCI Insight, 1982
- Resolution of diacylglycerol moieties of natural glycerophospholipids by gas–liquid chromatography on polar capillary columnsCanadian Journal of Biochemistry, 1982
- Rigid plasma‐membrane‐derived vesicles, enriched in tumour‐associated surface antigens (MLr), occurring in the ascites fluid of a murine leukaemia (GRSL)International Journal of Cancer, 1979
- Continuous growth and differentiation of human myeloid leukaemic cells in suspension cultureNature, 1977
- Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4Nature, 1970