Inhibition of Teleocidin-Caused Epidermal Ornithine Decarboxylase Induction by Phospholipase A2-, Cyclooxygenase- and Lipoxygenase-Inhibitors

Teleocidin (5 μg/mouse), a potent tumor promoting indole alkaloid from Streptomyces, induced epidermal ornithine decarboxylase (ODC) in CD-1 mice. Teleocidin-caused ODC induction was inhibited by the treatment of indomethacin (2 μmol/mouse), a selective cyclooxygenase inhibitor, and p-bromophenacyl bromide (BPB) (30 μmol/mouse), a phospholipase A2 inhibitor. Teleocidin-caused ODC induction inhibited by indomethacin was completely restored by concurrent application of prostaglandin E2 (PGE2) (140 nmol/mouse). On the other hand, teleocidin-caused ODC induction inhibited by BPB was not restored by the treatment of mice with PGE2, but partially restored by the treatment with arachidonic acid (1 μmol/mouse). Treatment of mice with lipoxygenase inhibitors such as BW755C (30 μmol/mouse), nordihydroguaiaretic acid (NDGA) (30 μmol/mouse), quercetin (10 μmol/mouse), and 2, 3, 5-trimethyl-6-(12-hydroxy-5, 10-dodecadiynyl)-1, 4-benzoqu1none (AA861) (10 μmol/mouse) clearly suppressed ODC induction by teleocidin. Moreover, both NDGA (30 μmol/mouse) and quercetin (10 μmol/mouse) inhibited the restoring effect of PGE2. Therefore, our present results suggest that arachidonate metabolites, i.e., not only cyclooxygenase product(s) but also lipoxygenase product(s), are involved in the mechanism of ODC induction by teleocidin.