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. Genistein suppressed H2O2 production by 12-O-tetradecanoylphorbol-13-acetate- (TPA) stimulated human polymorphonuclear leukocytes (PMNs) and HL-60 cells in a dose-dependent manner over the concentration range 1-150 microM. Human PMNs were more sensitive to the inhibitory effect of genistein than HL-60 cells (50% inhibitory concentration 14.8 and 30.2 microM, 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.
Wei
H
H
Department of Environmental Health Sciences, University of Alabama, Birmingham 35294.
Wei
L
L
Frenkel
K
K
Bowen
R
R
Barnes
S
S
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D016166:Free Radical Scavengers; D019833:Genistein; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007529:Isoflavones / Q000494:pharmacology*; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000494:pharmacology; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012871:Skin Diseases / Q000139:chemically induced / Q000188:drug therapy; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*; D014407:Tumor Cells, Cultured
D016588:Anticarcinogenic Agents; D016166:Free Radical Scavengers; D007529:Isoflavones; D017382:Reactive Oxygen Species; D013481:Superoxides; D006861:Hydrogen Peroxide; D019833:Genistein; D013755:Tetradecanoylphorbol Acetate