Inhibition of tumor Promoter‐induced hydrogen peroxide formation in vitro and in vivo by genistein

Abstract

Here we report that genistein, a soybean isoflavone, strongly inhibits tumor promoter‐induced H₂O₂ formation both in vivo and in vitro. Genistein suppressed H₂O₂ production by 12‐O‐tetrade‐canoylphorbol‐13‐acetate‐ (TPA) stimulated human polymorphonuclear leukocytes (PMNs) and HL‐60 cells in a dose‐dependent manner over the concentration range 1–150 μM. Human PMNs were more sensitive to the inhibitory effect of genistein than HL‐60 cells (50% inhibitory concentration 14.8 and 30.2 μM, respectively). In addition, genistein moderately inhibited Superoxide anion formation by HL‐60 cells and scavenged exogenously added H₂O₂ under the same conditions as in cell culture. However, the H₂O₂‐scavenging effect of genistein was about 50% lower than its inhibition of cell‐derived H₂O₂ formation at all concentrations. In the CD‐1 mouse skin model, genistein strongly inhibited TPA‐induced oxidant formation, edema, and PMN infiltration in mouse skin. Inhibition of TPA‐mediated H₂O₂ in vivo may result from decreased cell‐derived H₂O₂ formation, scavenging of H₂O₂ produced, and/or suppression of PMN infiltration into the dermis. The antioxidant properties of genistein may be responsible for its anticarcinogenic effects, and the dietary availability of genistein makes it a promising candidate for the prevention of human cancers.