Inhibition of 12-O-tetradecanoyl phorbol-13-acetate promoted tumorigenesis by cepharanthine, a biscoclaurine alkaloid, in relation to the inhibitory effect on protein kinase C.
In two-stage mouse skin carcinogenesis initiated by 7,12-dimethylbenz[alpha]anthracene (DMBA), cepharanthine inhibited the tumor promoting activity of 12-O-tetradecanoyl phorbol-13-acetate (TPA). Since Ca2(+)-phospholipid-dependent protein kinase (PKC) was shown to be an intracellular target of TPA, effects of cepharanthine on the activity of this enzyme were investigated Cepharanthine also inhibited the phosphorylation of H1 histone by PKC in a concentration dependent manner. While cepharanthine inhibited the association of H1 histone with phospholipid vesicles, autophosphorylation of PKC was not inhibited by this drug. Cepharanthine also inhibited TPA-stimulated phosphorylation of some cytoplasmic proteins of mouse skin epidermis. These results indicated the possibility that anti-tumor promoting action of cepharanthine was the result of inhibition of PKC dependent cytoplasmic protein phosphorylation through the reduction of the interaction of these proteins with the plasma membrane.
Edashige
K
K
Institute for Laboratory Animals, Kochi Medical School, Japan.
Utsumi
T
T
Utsumi
K
K
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D044182:Benzylisoquinolines; D003600:Cytosol / Q000378:metabolism; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006657:Histones / Q000378:metabolism; D051379:Mice; D010743:Phospholipids / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D012878:Skin Neoplasms / Q000139:chemically induced*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*; D052117:Benzodioxoles
D000470:Alkaloids; D044182:Benzylisoquinolines; D006657:Histones; D010743:Phospholipids; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; C006947:cepharanthine; D052117:Benzodioxoles