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A metabolite of an antineoplastic ether phospholipid may inhibit transmembrane signalling via protein kinase C

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Lipids

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.

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Abbreviations

AMG-PC:

1-O-alkyl-2-O-methylglycero-3-phosphocholine

AMG:

1-O-alkyl-2-O-methylglycerol

PKC:

protein kinase C

diC8 :

1,2-dioctanoyl-sn-glycerol

PS:

phosphatidylserine

PMSF:

phenylmethylsulfonyl fluoride

ATP:

adenosine 5′-triphosphate

PDBu:

3H-phorbol-12,13-dibutyrate

EGTA:

ethylene-glycol-bis(beta-aminoethylether)-N,N,N′,N′-tetraacetic acid

TLC:

thin layer chromatography

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Authors and Affiliations

  1. Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam, The Netherlands

    Ïjsbrand M. Kramer & Arthur J. Verhoeven

  2. Division of Cell Biology, The Netherlands Cancer Institute (Antoni van Leeuwenhoek-Huis), 121 Plesmanlaan, 1066 CX, Amsterdam, The Netherlands

    Wim J. van Blitterswijk, Rob L. van der Bend, Henk Hilkmann & John de Widt

Authors
  1. Wim J. van Blitterswijk
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  2. Rob L. van der Bend
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  3. Ïjsbrand M. Kramer
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  4. Arthur J. Verhoeven
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  5. Henk Hilkmann
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  6. John de Widt
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van Blitterswijk, W.J., van der Bend, R.L., Kramer, Ï.M. et al. A metabolite of an antineoplastic ether phospholipid may inhibit transmembrane signalling via protein kinase C. Lipids 22, 842–846 (1987). https://doi.org/10.1007/BF02535541

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  • DOI: https://doi.org/10.1007/BF02535541

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