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 ski n using 7,12-dimethylbenz[a]anthracene (0.19 mu mol) and 12-O-tetradec anoylphorbol-13-acetate (TPA; 1.6 nmol). Topical application of ACA (1 60 nmol) markedly reduced the average number of tumors per mouse and t he 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: i nhibitory ratio 44% (p < 0.05). ACA potently inhibited TPA-induced sup eroxide (O-2(-)) generation in differentiated HL-60 cells (IC50 = 4.3 mu M) and suppressed the lipid hydroperoxide formation by 42% (p < 0.0 01) in the ethyl linoleate autoxidation test.