Effect of structurally related flavones/isoflavones on hydrogen peroxide production and oxidative DNA damage in phorbol ester-stimulated HL-60 cells.
We have examined the antioxidant properties of structurally related flavones/isoflavones in 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated HL-60 cells. In the presence of 1.3% dimethyl sulfoxide in the medium for seven days, promyelocytic HL-60 cells were differentiated into neutrophil-like cells possessing phagocytic properties and the capacity to generate H2O2 on TPA stimulation. The effects of five selected flavones/isoflavones on the formation of H2O2 and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were examined in TPA-stimulated HL-60 cells. The results indicated that genistein was the most potent inhibitor of H2O2 production by TPA-stimulated HL-60 cells, followed by apigenin and daidzein, whereas prunectin and biochanin A exhibited no effect. This inhibitory effect correlates well with the scavenging capacity of H2O2 by these flavones/isoflavones in an in vitro system. The formation of 8-OHdG in cellular DNA of HL-60 cells was induced by TPA and further enhanced by the addition of FeCl2 to the medium. Most flavones/isoflavones significantly inhibited TPA + FeCl2-induced 8-OHdG formation in HL-60 cells, with genistein being the most potent quencher. The inhibition of H2O2 production and 8-OHdG formation by these structurally related flavones/isoflavones may contribute to their chemopreventive potentials against human cancers.
Giles
D
D
Department of Dermatology, Mount Sinai Medical Center, New York, NY 10029, USA.
Wei
H
H
D000080242:8-Hydroxy-2'-Deoxyguanosine; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000096:biosynthesis; D005419:Flavonoids / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007529:Isoflavones / Q000494:pharmacology*; D010084:Oxidation-Reduction; D013268:Stimulation, Chemical; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D005419:Flavonoids; D007529:Isoflavones; D000080242:8-Hydroxy-2'-Deoxyguanosine; D006861:Hydrogen Peroxide; D003849:Deoxyguanosine; D013755:Tetradecanoylphorbol Acetate