Open AccessThe mechanism of skin tumor promotion caused by phorbol esters: Possible involvement of arachidonic acid cascade/lipoxygenase, protein kinase C and calcium/calmodulin systems.
Author(s) -
Teruo Nakadate
Publication year - 1989
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.49.1
Subject(s) - tumor promotion , arachidonic acid , ornithine decarboxylase , protein kinase c , protein kinase a , calmodulin , lipoxygenase , biochemistry , 12 o tetradecanoylphorbol 13 acetate , calcium , chemistry , arachidonate 5 lipoxygenase , kinase , biology , pharmacology , enzyme , carcinogenesis , phorbol ester , organic chemistry , gene
12-O-Tetradecanoylphorbol-13-acetate (TPA) has been used as a potent tumor promoter in mouse skin. The mechanisms of TPA actions were studied by using several types of inhibitors. TPA-caused responses in mouse skin such as skin tumor promotion, epidermal ornithine decarboxylase (ODC) induction and skin inflammation were inhibited by various lipoxygenase inhibitors of the arachidonic acid cascade. Lipoxygenase inhibitors also inhibited TPA-caused ODC induction in isolated epidermal cells or cultured epidermal cells. Therefore, it is possible that these drugs inhibit TPA-caused ODC induction in mouse skin by directly acting on epidermal cells. TPA actions were also inhibited by either protein kinase C inhibitors, calmodulin antagonists or calcium blockers. These results suggest that arachidonic acid/lipoxygenase, protein kinase C and calcium-calmodulin systems play essential roles in the mechanism of tumor promotion by TPA.