Induction of the Phase II Detoxification Enzyme NQO1 in Hepatocarcinoma Cells by Lignans from the Fruit of<i>Schisandra chinensis</i>through Nuclear Accumulation of Nrf2

Lee, Saet Byoul; Kim, Chul Young; Lee, Hee Ju; Yun, Ji Ho; Nho, Chu Won

doi:10.1055/s-0029-1185685

Cited by 58 publications

(39 citation statements)

References 16 publications

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“…1) were purified as previously described. 20) Fruits of S. chinensis (250 g) were extracted 3 times with MeOH by sonication for 1 h. After filtration, the MeOH extract was evaporated and extracted with n-hexane and CH 2 Cl 2 consecutively. The n-hexane fraction (10 g) was chromatographed on an RP-18 column (4:5 Â 20 cm, 5:5-9:1 MeOH: water, v/v) to yield Fr.…”

Section: Methodsmentioning

confidence: 99%

Anti-Inflammatory Effects of Gomisin N, Gomisin J, and Schisandrin C Isolated from the Fruit ofSchisandra chinensis

Kim

Bae

et al. 2010

Bioscience, Biotechnology, and Biochemistry

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Section: Methodsmentioning

confidence: 99%

Anti-Inflammatory Effects of Gomisin N, Gomisin J, and Schisandrin C Isolated from the Fruit ofSchisandra chinensis

Kim

Bae

et al. 2010

Bioscience, Biotechnology, and Biochemistry

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“…They demonstrated that lipophilic extracts, containing ligustilide, and monooxygenated ligustilide, alkylated some key cysteine residues in the human Keap1 protein, thereby activating the NRF2 gene, and upregulating the transcription of ARE-regulated genes (76). Lee and co-workers also showed that lignans from the fruit of Schisandra chinensis led to a similar endpoint through nuclear accumulation of Nrf2 (77). A wide range of phytochemicals and other putative chemopreventive agents have been found to be anti-mutagens through similar mechanisms (17).…”

Section: Examples Of Mechanisms Of Anti-mutagen Protection Against DImentioning

confidence: 92%

Antimutagenesis Studies: Where Have They Been and Where Are They Heading?

Ferguson

2011

Genes and Environment

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An anti-mutagen is any substance that reduces the rate of spontaneous mutations or counteracts or reverses the action of a mutagen, or any technique that protects cells against the eŠects of mutagens. Studies as early as the 1940s reported on substances that delayed detection of radiation-induced mutations, or reduced the appearance of mutations induced by chemicals such as acridine orange. However, a far more sophisticated range of anti-mutagens is now being identiˆed. Mutagen scavengers act through absorption onto a larger molecule that is readily excreted. Good examples are provided by dietaryˆbre sources, such as wheat bran, or the planar molecule, chlorophyll and its stabilised derivative, chlorophyllin. Mutagens may be actively extruded from human cells through the action of one or more of a series of ATP-binding cassette (ABC) drug transporter proteins, including the multidrug resistance proteins (P-glycoproteins), multidrug resistance-associated proteins (MRP1-7) and the breast cancer resistance protein (BCRP). These proteins can aŠect the absorption, distribution and excretion of mutagens and carcinogens, as well as of their metabolites and conjugates. Even if the undesirable compound enters the cells, there are several mechanisms by which it may be prevented from interaction with DNA. Detoxiˆcation mechanisms are of increasing interest, especially those where transcription is regulated through the antioxidant response element (ARE), whose own transcription factor, Nrf2, is repressed under basal conditions. While much of the early literature on mutagenesis and carcinogenesis implicated exogenous chemicals, it is increasingly realised that unrepaired oxidative DNA lesions are important mutational precursors, and anti-oxidants represent an important class of anti-mutagens. It is also recognised that deˆciency of certain micronutrients may lead to cell mutation, and that restoring nutrient balance is an important mechanism of antimutagenesis. An increasing number of studies focus on DNA repair and stress responses as novel mechanisms of anti-mutagenesis.

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“…2A). 20) Furthermore, YA, YB, and YC showed a relatively high CI arising from low cytotoxicity (IC 50 Ͼ500 mM) and low CD values ( Table 3). The CI was determined by dividing the IC 50 (concentration required to inhibit cell growth by 50%) with the CD value (concentration required to double the QR activity).…”

Section: Increase In Qr Activity Exerted By Youngiasidesmentioning

confidence: 99%

Bi-Functional Induction of the Quinone Reductase and Cytochrome P450 1A1 by Youngiasides via Nrf2-ARE and AhR-XRE Pathways

Yun

Lee

et al. 2010

Biological & Pharmaceutical Bulletin

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Cancer chemoprevention is defined as the use of phytochemicals (naturally occurring compounds or their synthetic derivatives) from dietary foods or natural products to inhibit, delay or reverse carcinogenesis or prevent the development of cancer.1,2) The important strategy of cancer chemoprevention aims to reduce the risk of cancer through modulation of detoxification enzymes involved in metabolic activation. The detoxification/excretion of carcinogens is one of the representative mechanisms of action of chemopreventive agents. 3)Dietary phytochemicals can be classified into two groups, termed mono-and bi-functional inducers. Mono-functional inducers upregulate a number of phase II detoxification enzymes, including quinone reductase (QR, also known as NAD(P)H: quinone oxidoreductase, NQO1) and glutathione S-transferases (GSTs). The bi-functional inducers upregulate a similar array of phase II enzymes as well as a number of phase I enzymes including cytochrome P450 1A1 (CYP1A1). 4) Since phase I enzymes are involved in both bioactivation and detoxification of carcinogens, the monofunctional inducers, which upregulate only phase II enzymes, are thought to be more closely associated with chemoprevention than are bi-functional inducers that upregulate both phase I and II enzymes. However, the bi-functional inducers can in some cases exert synergistic effects in cancer chemoprevention. Oltpraz, a plant-derived compound, is a promising bi-functional inducer and is found to increase levels of not only phase II, but also phase I, enzymes. 5)These inducers are known to regulate genes that encode detoxification enzymes and which involve two important promoter sites. One site is known as the antioxidant response element (ARE) associated with induction of phase II detoxification enzymes (mono-functional induction), 6,7) while the second is the xenobiotic response element (XRE) located in the promoters of genes encoding phase II, and some phase I, cytochrome P450 enzymes (bi-functional induction). 8) AREand XRE-containing promoters can be activated by binding of specific transcription factors such as nuclear factor E2 (NF-E2) p45-Nrf2 and AhR, respectively. Nrf2 is a member of the CNC (cap'n'collar) basic leucine zipper (bZIP) transcription factor family and AhR is a member of the basic helix-loop-helix/Per-Arnt-Sim (bHLH/PAS) family. 9) Nrf2 is known to translocate into the nucleus and recruit Maf proteins, which is followed by the activation of transcription of ARE-dependent genes.10) The ligand-bound AhR translocates into the nucleus where it binds as a heterodimer with the AhR nuclear translocator (Arnt) and activates the transcription of XRE-dependent genes.11) In addition, it was recently revealed that Nrf2 is one of the AhR target genes. 12,13) In Korea, early sprouts have been used of the compositae plant Crepidiastrum denticulatum (HOUTT.) PAK & KAWANO; however, induction of QR by this plant has not yet been reported. Further, the chemical structures of youngiaside A, B, and C isolated from C. denticulatum have been...

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Induction of the Phase II Detoxification Enzyme NQO1 in Hepatocarcinoma Cells by Lignans from the Fruit ofSchisandra chinensisthrough Nuclear Accumulation of Nrf2

Cited by 58 publications

References 16 publications

Anti-Inflammatory Effects of Gomisin N, Gomisin J, and Schisandrin C Isolated from the Fruit ofSchisandra chinensis

Anti-Inflammatory Effects of Gomisin N, Gomisin J, and Schisandrin C Isolated from the Fruit ofSchisandra chinensis

Antimutagenesis Studies: Where Have They Been and Where Are They Heading?

Bi-Functional Induction of the Quinone Reductase and Cytochrome P450 1A1 by Youngiasides via Nrf2-ARE and AhR-XRE Pathways

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