Effects of flavonoids and antioxidants on 12-O-tetradecanoyl-phorbol-13-acetate-caused epidermal ornithine decarboxylase induction and tumor promotion in relation to lipoxygenase inhibition by these compounds
Nakadate, T.; Yamamoto, S.; Aizu, E.; Kato, R.
Gan 75(3): 214-222
1984
ISSN/ISBN: 0016-450X PMID: 6427052 Document Number: 221991
The effects of flavonoids, antioxidants and related compounds on 12-O-tetradecanoylphorbol-13-acetate (TPA)-caused epidermal ornithine decarboxylase (ODC) induction, DNA synthesis and skin tumor promotion, and on epidermal lipoxygenase activity, were investigated using CD-1 mice. Morin, fisetin, kaempferol and n-propyl gallate potently inhibited epidermal lipoxygenase activity, and esculetin, butylated hydroxyanisole (BHA), .alpha.-naphthol and 2,3-dihydroxynaphthalene (2,3-DHNA) moderately inhibited it. .alpha.-Tocopherol, (+)-catechin, (-)epicatechin and butylated hydroxytoluene (BHT) were inactive. Similarly, morin, fisetin, kaempferol and n-propyl gallate markedly inhibited TPA-caused ODC induction. Esculetin, BHA, .alpha.-naphthol, 2,3-DHNA and .alpha.-tocopherol inhibited it less potently, but significantly. (+)Catechin, (-)epicatechin and BHT failed to inhibit or only slightly inhibited TPA-caused ODC induction. TPA-caused DNA synthesis was not inhibited by morin, esculetin, (+)-catechin or .alpha.-tocopherol. The TPA-induced skin tumor promotion was markedly inhibited by morin and slightly suppressed by esculetin and .alpha.-tocopherol, but (+)-catechin was inactive. Thus, the inhibitory effects of flavonoids and antioxidants on the TPA-caused ODC induction and tumor promotion were roughly parallel with their activities of lipoxygenase inhibition. A lipoxygenase product(s) is probably involved in the mechanism of TPA-caused ODC induction and tumor promotion.