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 acid 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-alpha (TGF-alpha) and transforming growth factor-beta (TGF-beta). An antiserum to the EGF-receptor that blocks EGF binding partially inhibited the synergistic responses to palytoxin and EGF and palytoxin and TGF-alpha, whereas an antiserum to the EGF-receptor that does not block EGF binding or a non-immune rabbit serum did not.