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

• Published in: Lipids Vol. 22; no. 11; pp. 842 - 846
• Main Authors: Blitterswijk, Wim J., Bend, Rob L., Kramer, Ïjsbrand M., Verhoeven, Arthur J., Hilkmann, Henk, Widt, John
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer‐Verlag 01.11.1987
• Subjects: Animals; Antineoplastic Agents - pharmacology; Cell Line; Fibrosarcoma; Glyceryl Ethers - pharmacology; Mice; Mice, Inbred C3H; Neoplasm Invasiveness; Phorbol Esters - metabolism; Phospholipid Ethers - pharmacology; Protein Kinase C - metabolism; Tumor Cells, Cultured - drug effects; Tumor Cells, Cultured - enzymology
• ISSN: 0024-4201; 1558-9307
• 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 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.