Inhibition of protein kinase C by the 12-O-tetradecanoylphorbol-13-acetate antagonist glycyrrhetic acid.

Glycyrrhetic acid is an anti-inflammatory agent isolated from licorice root that inhibits 12-O-tetradecanoylphorbol-13-acetate (TPA)-mediated tumor promotion in mouse skin. Although it has been established that glycyrrhetic acid inhibits a number of events induced by the phorbol ester tumor promoter TPA in cultured cells, its mechanisms of action has remained obscure. In this report, we demonstrate that glycyrrhetic acid inhibits the Ca2+-and phospholipid-dependent phosphotransferase activity of protein kinase C (PKC), the phorbol ester tumor promoter receptor. Therefore, inhibition of PKC may play a role in the anti-promoting activity of glycyrrhetic acid.