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.
Janz
S
S
Laboratory of Genetics, National Cancer Institute, NIH, Bethesda, Maryland 20892.
Gawrisch
K
K
Lester
D S
DS
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