Enzymatic metabolites of lycopene induce Nrf2-mediated expression of phase II detoxifying/antioxidant enzymes in human bronchial epithelial cells.
Lycopene can be cleaved by carotene 9',10'-oxygenase at its 9',10' double bond to form apo-10'-lycopenoids, including apo-10'-lycopenal, -lycopenol and -lycopenoic acid. The latter has been recently shown to inhibit lung carcinogenesis both in vivo and in vitro, however, the mechanism(s) underlying this protection is not well defined. In the present study, we report that treatment with apo-10'-lycopenoic acid, in a time- and dose-dependent manner, results in the nuclear accumulation of transcription factor Nrf2 (nuclear factor E(2)-related factor 2) protein in BEAS-2B human bronchial epithelial cells. The activation of Nrf2 by apo-10'-lycopenoic acid is associated with the induction of phase II detoxifying/antioxidant enzymes including heme oxygenase-1, NAD(P)H:quinone oxidoreductase 1, glutathione S-transferases, and glutamate-cysteine ligases in BEAS-2B cells. Furthermore, apo-10'-lycopenoic acid treatment increased total intracellular glutathione levels and suppressed both endogenous reactive oxygen species generation and H(2)O(2)-induced oxidative damage in BEAS-2B cells. In addition, both apo-10'-lycopenol and apo-10'-lycopenal induced heme oxygenase-1 gene expression in BEAS-2B cells. These data strongly suggest that the anti-carcinogenic and antioxidant functions of lycopene may be mediated by apo-10'-lycopenoids via activating Nrf2 and inducing phase II detoxifying/antioxidant enzymes.
Lian
Fuzhi
F
Nutrition and Cancer Biology Laboratory, Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.
Wang
Xiang-Dong
XD
D016588:Anticarcinogenic Agents / Q000378:metabolism / Q000494:pharmacology*; D015153:Blotting, Western; D001980:Bronchi / Q000187:drug effects* / Q000201:enzymology; D002338:Carotenoids / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D005721:Glutamate-Cysteine Ligase / Q000187:drug effects / Q000378:metabolism; D005982:Glutathione Transferase / Q000187:drug effects / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D000077276:Lycopene; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000187:drug effects / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000201:enzymology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016588:Anticarcinogenic Agents; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D017382:Reactive Oxygen Species; D002338:Carotenoids; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D005982:Glutathione Transferase; D005721:Glutamate-Cysteine Ligase; D000077276:Lycopene