Protective effect of phytic acid on oxidative DNA damage with reference to cancer chemoprevention.
Phytic acid (myo-inositol hexaphosphate) is one of the most promising cancer chemopreventive agents. We investigated the mechanism by which phytic acid expresses preventive action to cancer. Phytic acid inhibited the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine in cultured cells treated with an H2O2-generating system, although it did not scavenge H2O2. Site-specific DNA damage by H2O2 and Cu(II) at GG and GGG sequences was inhibited by phytic acid, but not by myo-inositol. Phytic acid alone did not cause DNA damage and thus, it should not act as a prooxidant. We conclude that phytic acid acts as an antioxidant to inhibit the generation of reactive oxygen species from H2O2 by chelating metals, resulting in chemoprevention of cancer.
Midorikawa
K
K
Department of Hygiene, Mie University School of Medicine, Mie, 514-8507, Japan.
Murata
M
M
Oikawa
S
S
Hiraku
Y
Y
Kawanishi
S
S
D001665:Binding Sites; D018890:Chemoprevention; D003300:Copper / Q000494:pharmacology; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D004249:DNA Damage; D003839:Deoxyadenosines / Q000378:metabolism; D004347:Drug Interactions; D011905:Genes, ras / Q000235:genetics; D005949:Glucose Oxidase / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D009369:Neoplasms / Q000517:prevention & control; D010084:Oxidation-Reduction; D010833:Phytic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D020011:Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D003839:Deoxyadenosines; D020011:Protective Agents; D016159:Tumor Suppressor Protein p53; C078251:2'-deoxy-7,8-dihydro-8-oxoadenosine; D003300:Copper; D010833:Phytic Acid; D004247:DNA; D006861:Hydrogen Peroxide; D005949:Glucose Oxidase