Nuclear glutathione S-transferase π prevents apoptosis by reducing the oxidative stress-induced formation of exocyclic dna products

We previously found that nuclear glutathione S-transferase π (GSTπ) accumulates in cancer cells resistant to anticancer drugs, suggesting that it has a role in the acquisition of resistance to anticancer drugs. In the present study, the effect of oxidative stress on the nuclear translocation of GSTπ and its role in the protection of DNA from damage were investigated. In human colonic cancer HCT8 cells, the hydrogen peroxide (H2O2)-induced increase in nuclear condensation, the population of sub-G1 peak, and the number of TUNEL-positive cells were observed in cells pretreated with edible mushroom lectin, an inhibitor of the nuclear transport of GSTπ. The DNA damage and the formation of lipid peroxide were dependent on the dose of H2O2 and the incubation time. Immunological analysis showed that H2O2 induced the nuclear accumulation of GSTπ but not of glutathione peroxidase. Formation of the 7-(2-oxo-hepyl)-substituted 1,N2-etheno-2′-deoxyguanosine adduct by the reaction of 13-hydroperoxyoctadecadienoic acid (13-HPODE) with 2′-deoxyguanosine was inhibited by GSTπ in the presence of glutathione. The conjugation product of 4-oxo-2-nonenal, a lipid aldehyde of 13-HPODE, with GSH in the presence of GSTπ, was identified by LS/MS. These results suggested that nuclear GSTπ prevents H2O2-induced DNA damage by scavenging the formation of lipid-peroxide-modified DNA.