INHIBITION OF TUMOR PROMOTER-INDUCED HYDROGEN-PEROXIDE FORMATION IN-VITRO AND IN-VIVO BY GENISTEIN

Here we report that genistein, a soybean isoflavone, strongly inhibits tumor promoter-induced H2O2 formation both in vivo and in vitro. Geni stein suppressed H2O2 production by 12-O-tetradecanoylphorbol-13-aceta te- (TPA) stimulated human polymorphonuclear leukocytes (PMNs) and HL- 60 cells in a dose-dependent manner over the concentration range 1-150 muM. Human PMNs were more sensitive to the inhibitory effect of genis tein than HL-60 cells (50% inhibitory concentration 14.8 and 30.2 muM, respectively). In addition, genistein moderately inhibited superoxide anion formation by HL-60 cells and scavenged exogenously added H2O2 u nder the same conditions as in cell culture. However, the H2O2-scaveng ing effect of genistein was about 50% lower than its inhibition of cel l-derived H2O2 formation at all concentrations. In the CD-1 mouse skin model, genistein strongly inhibited TPA-induced oxidant formation, ed ema, and PMN infiltration in mouse skin. Inhibition of TPA-mediated H2 O2 in vivo may result from decreased cell-derived H2O2 formation, scav enging of H2O2 produced, and/or suppression of PMN infiltration into t he dermis. The antioxidant properties of genistein may be responsible for its anticarcinogenic effects, and the dietary availability of geni stein makes it a promising candidate for the prevention of human cance rs.