1'-acetoxychavicol acetate, a superoxide anion generation inhibitor, potently inhibits tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in ICR mouse skin

The anti-tumor-promoting activity of 1'-acetoxychavicol acetate (ACA) was examined in a two-stage carcinogenesis experiment in ICR mouse skin using 7,12-dimethylbenz[a]anthracene (0.19 mu mol) and 12-O-tetradecanoylphorbol-13-acetate (TPA; 1.6 nmol). Topical application of ACA (160 nmol) markedly reduced the average number of tumors per mouse and the ratio of tumor-bearing mice: inhibition ratios 90% (p < 0.001) and 42% (p < 0.005), respectively. ACA even at a dose equimolar to TPA(1.6 nmol) significantly reduced the average number of tumors per mouse: inhibitory ratio 44% (p < 0.05). ACA potently inhibited TPA-induced superoxide (O-2(-)) generation in differentiated HL-60 cells (IC50 = 4.3 mu M) and suppressed the lipid hydroperoxide formation by 42% (p < 0.001) in the ethyl linoleate autoxidation test.