Translocation and activation of protein kinase C by the plasma cell tumor-promoting alkane pristane.
Pristane (2,6,10,14-tetramethylpentadecane) is a C19-isoalkane that promotes the development of plasmacytomas in genetically susceptible BALB/c mice. Similarities between the effects of pristane and protein kinase C (PKC)-activating phorbol esters suggested that the tumor promoting activity of pristane might involve the activation of PKC. Here we show that up to 5 mol% of pristane can be homogeneously incorporated into phosphatidylcholine/phosphatidylserine bilayers. Membrane-incorporated pristane partially activated PKC and increased phorbol ester binding to the bilayer by more than 50%. Pristane (50 microM) delivered as an inclusion complex with beta-cyclodextrin to promyelocytic HL-60 leukemia cells induced a partial long-term translocation of PKC to the cell membrane. This was accompanied by differentiation of HL-60 cells into macrophage-like cells. It is concluded that activation of PKC may comprise an important aspect of the tumor promoting potential of pristane.
Laboratory of Genetics, National Cancer Institute, NIH, Bethesda, Maryland 20892.
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D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001921:Brain / Q000201:enzymology; D002273:Carcinogens / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006801:Humans; D007700:Kinetics; D015473:Leukemia, Promyelocytic, Acute; D008051:Lipid Bilayers; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D010766:Phosphorylation; D010954:Plasmacytoma / Q000139:chemically induced*; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D013347:Subcellular Fractions / Q000201:enzymology; D013729:Terpenes / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D002273:Carcinogens; D008051:Lipid Bilayers; D013729:Terpenes; C009042:pristane; D016718:Arachidonic Acid; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C