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Apo‐10′‐lycopenoic acid induces Nrf2‐mediated expression of phase II antioxidant genes and suppresses H2O2 induced oxidative damage in human bronchial epithelial cells
Author(s) -
Lian Fuzhi,
Wang XiangDong
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.451.7
Subject(s) - antioxidant , glutathione , chemistry , oxidative stress , reactive oxygen species , biochemistry , nad+ kinase , oxidative phosphorylation , lactate dehydrogenase , enzyme , heme oxygenase , carcinogenesis , keap1 , catalase , microbiology and biotechnology , transcription factor , biology , heme , gene
Our previous study has demonstrated that apo‐10′‐lycopenoic acid (ALA), an enzymatic metabolite of lycopene, can suppress lung carcinogenesis in an animal model. However, the potential mechanism(s) underlying this protection is not well defined. It has been suggested that lycopene or its hydrophilic derivatives induce phase II detoxification and antioxidant enzymes by activating the transcription factor Nrf2 (nuclear factor E2‐related factor 2). In this study, we investigated whether purified ALA induces Nrf2‐mediated expression of phase II antioxidant genes and protects against H2O2‐induced oxidative damage. We found that ALA treatment significantly induced the expressions of several phase II enzymes (glutamate‐cysteine ligases, heme oxygenase‐1, and NAD(P)H : quinone oxidoreductase 1) and resulted in the nuclear accumulation of Nrf2 protein in a time‐ and dose‐dependent manner in BEAS‐2B human bronchial epithelial cells. Accordingly, ALA treatment increased total glutathione levels and suppressed endogenous reactive oxygen species generation in BEAS‐2B cells. Furthermore, pretreatment of ALA suppressed H2O2‐induced oxidative damage in BEAS‐2B cells as measured by lactate dehydrogenase releasing assay. In conclusion, these data suggest that ALA inhibits lung carcinogenesis by activating Nrf2 mediated antioxidant defense system. (Supported by NIH grant R01CA104932).