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  • Title: The carotenoid lycopene differentially regulates phase I and II enzymes in dimethylbenz[a]anthracene-induced MCF-7 cells.
    Author: Wang H, Leung LK.
    Journal: Nutrition; 2010; 26(11-12):1181-7. PubMed ID: 20400267.
    Abstract:
    OBJECTIVE: Lycopene is a carotenoid widely distributed in fruit and vegetables. Epidemiological studies suggest that lycopene consumption is associated with decreased cancer risk. Animal studies have revealed that lycopene may protect against dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis in the breast. Polycylic aromatic hydrocarbons (PAH) are environmental toxicants that can be metabolized by two phase I enzymes, cytochrome P450 1A1 and 1B1. Products formed by these reactions are DNA-attacking moieties. Mutation generated by these genotoxic intermediates is believed to be an important step in cancer initiation. Some phase II detoxifying enzymes, such as uridine diphosphate (UDP)-glucuronosyltransferases (UGT), facilitate the elimination of these genotoxic moieties. In the present study, the mechanism by which lycopene prevented PAH-induced carcinogenesis in the breast was investigated in a cell culture model MCF-7. RESEARCH METHODS AND PROCEDURES: The inhibitory action of lycopene on CYP1 enzymes was assessed in recombinant protein and cell culture using ethoxyresorufin-O-deethylase assay. Messenger RNA expressions of CYP1A1 and 1B1, and UGT were estimated by semi-quantitative reverse transcription-polymerase chain reaction. Cells were co-treated with tritiated DMBA and lycopene for quantifying the protection of the phytocompound against DNA lesion generated from the DMBA metabolites. RESULTS: Lycopene inhibited recombinant CYP1A1 and CYP1B1 with estimated K(i)s in the micromolar range. In MCF-7 cells, lycopene administration slightly reduced the DMBA-induced ethoxyresorufin-O-deethylase activity by 20%. Meanwhile, a four-fold increase in microsomal UGT activity was observed. CONCLUSION: The present study illustrated that phase I enzyme inhibition and phase II enzyme induction were the underlying chemoprotective mechanisms of lycopene against PAH-induced toxicity.
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