Inhibition of biological actions of 12-O-tetradecanoylphorbol-13-acetate by inhibitors of protein kinase C.

Evidence has been accumulated that the phorbol ester receptor in intact cells is protein kinase C. However, it is not certain whether the various actions of 12-O-tetradecanoylphorbol-13-acetate (TPA) on cultured cells are all mediated by the activation of protein kinase C. Therefore, we examined the effects of inhibitors of protein kinase C, palmitoylcarnitine (PC) and phloretin (PH), on several actions of TPA on cells. PC at the concentration of 30 micrograms/ml completely prevented the inhibitory actions of TPA on differentiation of Friend leukemic cells (FLC) induced by hexamethylene bisacetamide (HMBA) and on metabolic cooperation of V79 cells. PC, however, did not prevent the TPA-induced promotion of the transformation of BALB/3T3 cells, even at the concentration of 40 micrograms/ml. On the other hand, PH at the concentration of 30 micrograms/ml did not inhibit the actions of TPA to inhibit differentiation of FLC and metabolic cooperation of V79 cells, but completely inhibited the transformation of BALB/3T3 cells and its promotion by TPA. These results indicate that protein kinase C possibly mediates some of the actions of TPA, such as the inhibition of differentiation and metabolic cooperation, but not that of the promotion of in vitro transformation.