Phorbol ester-induced leukotriene biosynthesis and tumor promotion in mouse epidermis.
In mouse skin in vivo the irritant and hyperplasiogenic tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) strongly increased the epidermal content of the cysteinyl leukotrienes LTC4, LTD4 and LTE4, but not of leukotriene LTB4. This effect was completely suppressed by the selective leukotriene biosynthesis inhibitor MK-886. Intragastric administration of MK-886 prevented phorbol ester-induced ear edema, but not epidermal hyperproliferation and tumor promotion. These data indicate that leukotrienes are involved in the pro-inflammatory effects of the phorbol ester, whereas its hyperproliferative and tumor-promoting activities do not depend on 5-lipoxygenase-catalyzed leukotriene formation. This action differs from several non-selective inhibitors of lipoxygenases that were found to inhibit tumor promotion in initiated mouse skin.
Fürstenberger
G
G
Research Program on Tumor Cell Regulation, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Csuk-Glänzer
B I
BI
Marks
F
F
Keppler
D
D
D000818:Animals; D004431:Ear, External; D004487:Edema / Q000139:chemically induced; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006965:Hyperplasia; D007211:Indoles / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced; D007975:Leukotriene B4 / Q000096:biosynthesis; D051379:Mice; D013189:SRS-A / Q000096:biosynthesis*; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000633:toxicity*; D002722:Chlorobenzenes
D007211:Indoles; D007975:Leukotriene B4; D013189:SRS-A; D013755:Tetradecanoylphorbol Acetate; C060893:MK-886; D002722:Chlorobenzenes