Cremophor EL, a widely used parenteral vehicle, is a potent inhibitor of protein kinase C.
Cremophor EL, a castor oil derivative, has been considered a non-toxic solubilizer for lipophilic drugs and vitamins. Protein kinase C, a phospholipid/Ca++-dependent protein kinase, is known to phosphorylate, in response to extracellular stimuli, a variety of proteins for cellular functions. The present study shows that Cremophor EL selectively inhibits the activity of protein kinase C in vitro. The potency of this selective inhibition is greater than that of other protein kinase C-specific inhibitor thus far reported. Cremophor EL acts primarily on the enzyme activator diacylglycerol (or the phorbol ester) and prevents the latter from both interacting with the phospholipid and binding to protein kinase C. This is the first report of a significant biological activity induced by this widely used substituted castor oil solubilizer.
Zhao
F K
FK
Department of Pharmacology, School of Medicine, University of California, Davis 95616.
Chuang
L F
LF
Israel
M
M
Chuang
R Y
RY
D001667:Binding, Competitive; D002460:Cell Line; D004257:DNA Polymerase II / Q000378:metabolism; D004337:Drug Carriers; D005990:Glycerol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D007938:Leukemia; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D011485:Protein Binding; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D011494:Protein Kinases / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D012997:Solvents; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004337:Drug Carriers; D012997:Solvents; D015240:Phorbol 12,13-Dibutyrate; C000515:cremophor EL; D011494:Protein Kinases; D011493:Protein Kinase C; D012319:RNA Polymerase II; D004257:DNA Polymerase II; D013755:Tetradecanoylphorbol Acetate; D005990:Glycerol