Inhibition of teleocidin-caused epidermal ornithine decarboxylase induction by phospholipase A2-, cyclooxygenase- and lipoxygenase-inhibitors.
Teleocidin (5 micrograms/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 mumol/mouse), a selective cyclooxygenase inhibitor, and p-bromophenacyl bromide (BPB) (30 mumol/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 mumol/mouse). Treatment of mice with lipoxygenase inhibitors such as BW755C (30 mumol/mouse), nordihydroguaiaretic acid (NDGA) (30 mumol/mouse), quercetin (10 mumol/mouse), and 2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone (AA861) (10 mumol/mouse) clearly suppressed ODC induction by teleocidin. Moreover, both NDGA (30 mumol/mouse) and quercetin (10 mumol/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.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002273:Carcinogens / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors; D004790:Enzyme Induction / Q000187:drug effects; D004817:Epidermis / Q000201:enzymology*; D005260:Female; D016859:Lipoxygenase Inhibitors; D008235:Lyngbya Toxins / Q000037:antagonists & inhibitors*; D051379:Mice; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2
D001095:Arachidonic Acids; D002273:Carcinogens; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D008235:Lyngbya Toxins; C022176:teleocidins; D016718:Arachidonic Acid; D010741:Phospholipases A; D054467:Phospholipases A2; D009955:Ornithine Decarboxylase