Apo-8′-lycopenal Induces Expression of HO-1 and NQO-1 via the ERK/p38-Nrf2-ARE Pathway in Human HepG2 Cells

Yang, Chang‐Hsien; Huang, Shang-Ming; Liu, Cheng-Ling; Hu, Miao‐Lin

doi:10.1021/jf204451n

Cited by 48 publications

(40 citation statements)

References 65 publications

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“…Thus, this pattern suggests that lycopene cleavage metabolites produced by BCO2 may have anti-prostate-cancer bioactivity and that their production is diminished in the Bco2−/− mice. Previous studies on the effect of the lycopene metabolite, apo-10’-lycopenoic acid, have shown it to reduce hepatic inflammation, steatosis, and tumorigenesis in mice (60, 61), and other studies of apo-8’-lycopenal in models of liver cancer have been indicative of bioactivity (38, 39), increasing the plausibility of lycopene metabolite activity in the prostate. We also demonstrate that tomato-fed Bco2−/− accumulate lycopene precursors, phytofluene, zeta-carotene, and a suggestion for phytoene, opening the door for hypotheses regarding the potential for BCO2 to cleave additional carotenoids.…”

Section: Discussionmentioning

confidence: 99%

β-Carotene 9′,10′ Oxygenase Modulates the Anticancer Activity of Dietary Tomato or Lycopene on Prostate Carcinogenesis in the TRAMP Model

Tan

Thomas‐Ahner

Moran

et al. 2017

Cancer Prevention Research

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The hypothesis that dietary tomato consumption or the intake of the carotenoid lycopene inhibits prostate cancer arose from epidemiologic studies and is supported by preclinical rodent experiments and in vitro mechanistic studies. We hypothesize that variation in activity of carotenoid cleavage enzymes, such as β-carotene 9’,10’-oxygenase (BCO2), may alter the impact of dietary tomato and lycopene on prostate carcinogenesis and therefore examined this relationship in the TRAMP model. Starting at three weeks of age, TRAMP:Bco2+/+ and TRAMP:Bco2−/− mice were fed either AIN-93G control, or semi-purified diets containing 10% tomato powder or 0.25% lycopene beadlets until 18 weeks of age. Both tomato- and lycopene-fed TRAMP:Bco2−/− mice had significantly greater serum concentrations of total, 5-cis, other cis, and all-trans lycopene than TRAMP:Bco2+/+ mice. Tomato- and lycopene-fed mice had a lower incidence of prostate cancer compared to the control-fed mice. While Bco2 genotype alone did not significantly change prostate cancer outcome in the control AIN-93G-fed mice, the abilities of lycopene and tomato feeding to inhibit prostate carcinogenesis were significantly attenuated by the loss of Bco2 (interaction p=0.0004 and p=0.0383, respectively). Overall, dietary tomato and lycopene inhibited the progression of prostate cancer in TRAMP in a Bco2 genotype-specific manner, potentially implicating the anticancer activity of lycopene cleavage products. This study suggests that genetic variables impacting carotenoid metabolism and accumulation can impact anti-cancer activity and that future efforts devoted to understanding the interface between tomato carotenoid intake, host genetics, and metabolism will be necessary to clearly elucidate their interactive roles in human prostate carcinogenesis.

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Section: Discussionmentioning

confidence: 99%

β-Carotene 9′,10′ Oxygenase Modulates the Anticancer Activity of Dietary Tomato or Lycopene on Prostate Carcinogenesis in the TRAMP Model

Tan

Thomas‐Ahner

Moran

et al. 2017

Cancer Prevention Research

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“…The possibility of polyphenols in PB such as chavicol or euginol inducing Nrf2 was also reported by a study of Tsai et al, who showed that phenolic compounds from rosemary and carnosic acid induced transcription of Nrf2, ARE luciferase reporter activity and increased expression of NQO1 gene and protein in rat clone 9 cells [41]. Lycopene metabolite, apo-8’-lycopenal that can be found in rat liver and human plasma after consuming lycopene-containing food, induced nuclear translocation, Nrf2-ARE binding activity, HO-1 and NQO1 genes and proteins expression in human hepatoma cell lines, HepG2 [42]. The isothiocyanate, sulforaphane and the flavonoid, epigenin increased gene expression of phase II detoxifying enzyme such as glutathione S-transferase (GSTA1) and UDP-glucuronosyltransferase (UGT1A1) in human colon adenocarcinoma [43].…”

Section: Discussionmentioning

confidence: 99%

Piper betle induces phase I & II genes through Nrf2/ARE signaling pathway in mouse embryonic fibroblasts derived from wild type and Nrf2 knockout cells

Hasan¹,

Kwak²,

Makpol³

et al. 2014

BMC Complement Altern Med

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BackgroundNuclear factor-erythroid 2 p45 related factor 2 (Nrf2) is a primary transcription factor, protecting cells from oxidative stress by regulating a number of antioxidants and phase II detoxifying enzymes. Dietary components such as sulforaphane in broccoli and quercetin in onions have been shown to be inducers of Nrf2. Piper betle (PB) grows well in tropical climate and the leaves are used in a number of traditional remedies for the treatment of stomach ailments and infections among Asians. The aim of this study was to elucidate the effect of Piper betle (PB) leaves extract in Nrf2 signaling pathway by using 2 types of cells; mouse embryonic fibroblasts (MEFs) derived from wild-type (WT) and Nrf2 knockout (N0) mice.MethodsWT and N0 cells were treated with 5 and 10 μg/ml of PB for 10 and 12-h for the determination of nuclear translocation of Nrf2 protein. Luciferase reporter gene activity was performed to evaluate the antioxidant response element (ARE)-induction by PB. Real-time PCR and Western blot were conducted on both WT and N0 cells after PB treatment for the determination of antioxidant enzymes [superoxide dismutase (SOD1) and heme-oxygenase (HO-1)], phase I oxidoreductase enzymes [NAD(P)H: quinone oxidoreductase (NQO1)] and phase II detoxifying enzyme [glutathione S-transferase (GST)].ResultsNuclear translocation of Nrf2 by PB in WT cells was better after 10 h incubation compared to 12 h. Real time PCR and Western blot analysis showed increased expressions of Nrf2, NQO1 and GSTA1 genes with corresponding increases in glutathione, NQO1 and HO-1 proteins in WT cells. Reporter gene ARE was stimulated by PB as shown by ARE/luciferase assay. Interestingly, PB induced SOD1 gene and protein expressions in N0 cells but not in WT cells.ConclusionThe results of this study confirmed that PB activated Nrf2-ARE signaling pathway which subsequently induced some phase I oxidoreductase, phase II detoxifying and antioxidant genes expression via ARE reporter gene involved in the Nrf2 pathway with the exception of SOD1 which may not be dependent on this pathway.

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“…As shown in Table , ERK can be phosphorylated by fruit and vegetable constituents, such as quercetin, sulforaphane/PEITC, diallyl sulfide, hydroxytyrosol, resveratrol, lycopene, luteolin, procyanidin B2, anthocyanins, hesperidin, and ferulic acid; by herb constituents, such as α‐iso‐cubebenol, schisandrin B, oleanolic acid, eupatilin, Aralia continentalis extract, rottlerin, acteoside, tanshinone IIA, celastrol, and red ginseng extract; by tea and spice constituents, such as EGCG, epicatechin, lindenenyl acetate; and by marine products, such as eckol and fucoxanthin. p38 MAPK is also activated by fruit and vegetable constituents, such as quercetin, sulforaphane, diallyl sulfide, carnosic acid, lycopene, procyanidin B2, fisetin, and sesamin/episesamin; by herb constituents, such as Aralia continentalis extract, ginkgo biloba extract, rottlerin, celastrol, and mollugin; by tea and coffee constituents, such as EGCG and kahweol; by spices, such as curcumin and piperine; and by marine product like fucoxanthin.…”

Section: Molecular Mechanisms Of Nrf2 Activation and Dynamic Regulatimentioning

confidence: 99%

Multiple regulations of Keap1/Nrf2 system by dietary phytochemicals

Qin

Hou

2016

Molecular Nutrition Food Res

159

111

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Keap1/Nrf2 system plays a critical role on cellular protection by regulating many antioxidant and detoxification enzyme genes through the antioxidant response element (ARE). Thus, it must work constantly to prevent the accumulation of reactive oxygen species (ROS) because excess ROS are associated with many diseases such as cancer, cardiovascular complications, inflammation, and neurodegeneration. Dietary phytochemicals widely distributing in fruits and vegetables have been considered to possess cancer chemopreventive potential through the induction of Keap1/Nrf2 system-mediated antioxidant and detoxification enzymes in a variety of manners. The data are extensive and are not well classified on the molecular mechanisms. In this review, we first briefly introduce the current knowledge on Keap1/Nrf2 system regulation including Keap1-dependent and Keap1-independent cascades, and epigenetic pathway. Then, we summarize the molecular targets of Keap1/Nrf2 system by dietary phytochemicals, and finally review the crosstalk between Keap1/Nrf2 system and other cellular signaling pathways to regulate diverse chronic diseases by dietary phytochemicals. These comprehensive data will help us to understand the potential effects of dietary phytochemicals on the prevention of chronic diseases and maintenance of human health.

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Apo-8′-lycopenal Induces Expression of HO-1 and NQO-1 via the ERK/p38-Nrf2-ARE Pathway in Human HepG2 Cells

Cited by 48 publications

References 65 publications

β-Carotene 9′,10′ Oxygenase Modulates the Anticancer Activity of Dietary Tomato or Lycopene on Prostate Carcinogenesis in the TRAMP Model

β-Carotene 9′,10′ Oxygenase Modulates the Anticancer Activity of Dietary Tomato or Lycopene on Prostate Carcinogenesis in the TRAMP Model

Piper betle induces phase I & II genes through Nrf2/ARE signaling pathway in mouse embryonic fibroblasts derived from wild type and Nrf2 knockout cells

Multiple regulations of Keap1/Nrf2 system by dietary phytochemicals

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