Mangiferin Reduced Etoposide-induced DNA Damage In Mononuclear Human Umbilical Cord Blood Cells Via Activating Nrf2-ARE Signaling

Purpose: To evaluate the protective role of mangiferin against VP-16 induced DNA damage in normal human cord blood cells via effecting on Nrf2/ARE antioxidant response signaling pathway and further investigate potential molecular mechanism of mangiferin prevention against leukemia.Methods: Normal human cord blood cells were isolated by HAES steril in vitro. VP-16 Groups (non MA pretreatment) and MA+VP-16 groups (MA pretreatment) were designed. DNA damage was measured by Single cell gel electrophoresis (SCGE) which also called comet assay and micronuclei (MN) assay respectively. Nrf2 nucleic localization was detected by indirect immunofluorescence (confocal microscope). The Nrf2 specially binding to ARE was checked out by EMSA and expression of Nrf2 and NQO1 proteins were detected by western blotting.Results: The levels of DNA damage are found to be high in VP-16 groups when compared to negative control groups in a time and does dependent manner in vitro. However, cells pretreatment with mangiferin showed that the levels of DNA damage were all decreased. Different treatment times and doses of mangiferin all activated the nuclear accumulation of Nrf2, following with nuclear Nrf2 binding to nuclear cis-acting enhancer called antioxidant response element–ARE. The expression of detoxification enzyme NQO1 was also increased by MA in a time dependent manner.Conclusion: Mangiferin can reduce and protect against DNA damage induced by chemical carcinogens such as VP-16 via activating Nrf2/ARE antioxidant response signaling pathway. Thus This newly identified Nrf2 activator can be a potential chemopreventive agent against tumor especially therapy-related leukemia which deserves further study.