Stimulation of arachidonic acid metabolism by different types of tumor promoters

Abstract

Skin tumor-promoting agents, including the 12-O-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoters, such as diterpine phorbol esters, teleocidin and aplysiatoxin, and a non-TPA-type tumor promoter (the newly described palytoxin, present in the coelenterate of the genus Palythoa), stimulated arachidonic acid metabolism by rat liver cells in culture. Palytoxin was 1000–3000 times more effective than TPA-type tumor promoters. The stimulations of arachidonic add metabolism by palytoxin and the TPA-type tumor promoters were synergistic, whereas the stimulations among the TPA-type tumor promoters were not. The stimulation of arachidonic acid metabolism by palytoxin was synergistic with that of epidermal growth factor (EGF), transforming growth factor-α (TGF-α) and transforming growth factor-β (TGF-β). An antiserum to the EGF-receptor that blocks EGF binding partially inhibited the synergistic responses to palytoxin and EGF and palytoxin and TGF-α, whereas an antiserum to the EGF-receptor that does not block EGF binding or a non-immune rabbit serum did not.