title: Apo-8'-lycopenal induces expression of HO-1 and NQO-1 via the ERK/p38-Nrf2-ARE pathway in human HepG2 cells.
abstract: Lycopene and its metabolite apo-10'-lycopenoic acid have been shown to induce phase II detoxifying/antioxidant enzymes through activation of the nuclear factor erythroid-derived 2-like 2 (Nrf2)-antioxidant response element (ARE) transcription system. However, little is known about whether apo-8'-lyocpenal, one of the main metabolites of lycopene in rat livers, in lycopene-containing food, and in human plasma, has similar effects. This study investigated the effect of apo-8'-lycopenal on Nrf2-ARE system-mediated heme oxygenase 1 (HO-1) and NAD(P)H:quinine oxidoreductase 1 (NQO-1) expression in human HepG2 cells. It was found that apo-8'-lycopenal (1-10 μM) significantly increased nuclear Nrf2 accumulation, ARE-luciferase activity, Nrf2-ARE binding activity, chymotrypsin-like activity, and downstream HO-1 and NQO-1 expression, but decreased cytosolic Kelch-like ECH-associated protein 1 (Keap1) expression. Results also revealed that the ERK/p38-Nrf2 pathway is involved in activation of HO-1 and NQO-1 expression by apo-8'-lycopenal using Nrf2 siRNA and ERK/p38 specific inhibitors. In addition, the activation time of lycopene on nuclear Nrf2 accumulation is slower than that of apo-8'-lycopenal, suggesting that the chemopreventive effects of lycopene may be partially attributed to its metabolites.
authors.affiliation: Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Chih-Min
authors.initials: CM
authors.lastname: Yang
authors.forename: Shu-Ming
authors.initials: SM
authors.lastname: Huang
authors.forename: Cheng-Ling
authors.initials: CL
authors.lastname: Liu
authors.forename: Miao-Lin
authors.initials: ML
authors.lastname: Hu
mesh_terms: D016588:Anticarcinogenic Agents; D000975:Antioxidants / Q000494:pharmacology; D002338:Carotenoids / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D051547:Heme Oxygenase-1 / Q000235:genetics*; D056945:Hep G2 Cells; D006801:Humans; D000077276:Lycopene; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D020218:Response Elements / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D016588:Anticarcinogenic Agents; D000975:Antioxidants; D005231:Fatty Acids, Unsaturated; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C523199:apo-10'-lycopenoic acid; C572536:apo-8'-lycopenal; D002338:Carotenoids; D051547:Heme Oxygenase-1; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D000077276:Lycopene