Effects of hexadecylphosphocholine on protein kinase C and TPA-induced differentiation of HL60 cells.
Several structural analogs of alkylphosphocholine (APC) were studied for their effects on protein kinase C (PKC) and 12-O-tetradecanoylphorbol-13-acetate (TPA) elicited biochemical and cellular events in HL60 cells. Hexadecylphocholine (He-PC2), the APC prototype, inhibited PKC competitively with respect to phosphatidylserine an noncompetitively with respect to CaCl2, both with an apparent Ki of about 15 microM. Inhibition of PKC by He-PC2 was selective, since cyclic AMP dependent protein kinase and Ca2+/calmodulin dependent protein kinase II were relatively unaffected. He-PC2 inhibited TPA-induced depletion of PKC and TPA-stimulated phosphorylation of cellular proteins in HL60 cells. TPA-induced differentiation of HL60 cells was also inhibited by He-PC2, and this inhibition was synergistic or additive to the effects of 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7), a PKC inhibitor. The present findings are consistent with the hypothesis that inhibition of PKC might be related, in part, to the antineoplastic effect of He-PC2 and ether lipid analogs such as ET-18-OCH3 (1-octadecyl-2-methyl-glycero-3-phosphocholine).
Shoji
M
M
Department of Medicine (Hematology/Oncology), Emory University School of Medicine, Atlanta, Georgia 30322.
Raynor
R L
RL
Fleer
E A
EA
Eibl
H
H
Vogler
W R
WR
Kuo
J F
JF
D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D006801:Humans; D007700:Kinetics; D015473:Leukemia, Promyelocytic, Acute; D010742:Phospholipid Ethers / Q000494:pharmacology; D010750:Phosphoproteins / Q000302:isolation & purification; D010766:Phosphorylation; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D010742:Phospholipid Ethers; D010750:Phosphoproteins; D010767:Phosphorylcholine; C026659:edelfosine; C039128:miltefosine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate