Effect of structurally related flavones/isoflavones on hydrogen peroxide production and oxidative DNA damage in phorbol ester‐stimulated HL‐60 cells

Abstract

We have examined the antioxidant properties of structurally related flavones/isoflavones in 12‐O‐tetradec‐anoylphorbol‐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 biochaninA 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.