Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion and epidermal ornithine decarboxylase activity in mouse skin by palmitoylcarnitine.
Palmitoylcarnitine, which has been reported to be an inhibitor of calcium-activated, phospholipid-dependent protein kinase (protein kinase C), inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced epidermal ornithine decarboxylase in mouse skin in a dose-dependent manner. Neither acetylcarnitine nor palmitic acid inhibited TPA-caused ornithine decarboxylase induction. In addition, palmitoylcarnitine markedly inhibited skin tumor promotion induced by TPA. Palmitoylcarnitine inhibited epidermal protein kinase C activity which was stimulated by Ca2+ in the presence of phosphatidylserine but failed to inhibit the enzyme activity which was stimulated by TPA in the presence of either phosphatidylserine or Ca2+ plus phosphatidylserine. Therefore, it seems unlikely that the potent anti-tumor-promoting action of palmitoylcarnitine, which is shown in the present study, is explained solely by its effect on protein kinase C.
Nakadate
T
T
Yamamoto
S
S
Aizu
E
E
Kato
R
R
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002331:Carnitine / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D009955:Ornithine Decarboxylase / Q000032:analysis; D065108:Ornithine Decarboxylase Inhibitors; D010172:Palmitoylcarnitine / Q000494:pharmacology*; D010704:Phorbols / Q000037:antagonists & inhibitors*; D011493:Protein Kinase C / Q000032:analysis / Q000037:antagonists & inhibitors; D012867:Skin / Q000201:enzymology*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors*; D013997:Time Factors
D065108:Ornithine Decarboxylase Inhibitors; D010704:Phorbols; D010172:Palmitoylcarnitine; D004533:Egtazic Acid; D011493:Protein Kinase C; D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate; D002331:Carnitine; D002118:Calcium