ArticleToxicology letters2009
Comparison of citrus coumarins on carcinogen-detoxifying enzymes in Nrf2 knockout mice.
Article in Toxicology letters, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 65 citations in OpenAlex.
- A systems-level integration of liver-kidney transcriptomics and genome-scale metabolic models reveals organ-specific injury mechanisms.Frontiers in toxicology · 2026Article
- Activation of Nrf2 and FXR via Natural Compounds in Liver Inflammatory Disease.International journal of molecular sciences · 2024Review
- Effects of Dietary Docosahexaenoic Acid (DHA) Levels on Growth Performance, Fatty Acid Profile, and NF-Aquaculture nutrition · 2024Article
- The Antioxidant Auraptene Improves Aged Oocyte Quality and Embryo Development in Mice.Antioxidants (Basel, Switzerland) · 2022Article
- Auraptene, a Monoterpene Coumarin, Inhibits LTA-Induced Inflammatory Mediators via Modulating NF-Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway.Oxidative medicine and cellular longevity · 2020Review
- Article
- [Effects of daphnetin combined with insulin-like growth factor 1 on chondrogenic differentiation of adipose-derived mesenchymal stem cells in rats].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2019Article
- Auraptene Inhibits Migration and Invasion of Cervical and Ovarian Cancer Cells by Repression of Matrix Metalloproteinasas 2 and 9 Activity.Journal of pharmacopuncture · 2018Article
- New hits as phase II enzymes inducers from a focused library with heteroatom-heteroatom and Michael-acceptor motives.Future science OA · 2015Article
- Citrus fruits as a treasure trove of active natural metabolites that potentially provide benefits for human health.Chemistry Central journal · 2015Review
- Small molecule modulators of Keap1-Nrf2-ARE pathway as potential preventive and therapeutic agents.Medicinal research reviews · 2012Review
- Effects of Auraptene on IGF-1 Stimulated Cell Cycle Progression in the Human Breast Cancer Cell Line, MCF-7.International journal of breast cancer · 2012Article
- Therapeutic potential and anti-amyloidosis mechanisms of tert-butylhydroquinone for Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2011Article
- Aggressive mammary carcinoma progression in Nrf2 knockout mice treated with 7,12-dimethylbenz[a]anthracene.BMC cancer · 2010Article
- Effects of ATRA combined with citrus and ginger-derived compounds in human SCC xenografts.BMC cancer · 2010Article
- Hydrogen sulfide mediates cardioprotection through Nrf2 signaling.Circulation research · 2009Article
- Citrus auraptene suppresses cyclin D1 and significantly delays N-methyl nitrosourea induced mammary carcinogenesis in female Sprague-Dawley rats.BMC cancer · 2009Article
- Imperatorin-pharmacological meaning and analytical clues: profound investigation.Phytochemistry reviews : proceedings of the Phytochemical Society of EuropeReview
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Naturally occurring coumarins possess anti-carcinogenic activities in part by inducing carcinogen-detoxifying enzymes glutathione S-transferase (GST) and/or NAD(P)H quinone oxidoreductase (NQO1). Our goal was to determine whether citrus coumarins induce hepatic GST and/or NQO1 via activation of Nrf2 and the antioxidant response element (ARE). First, HepG2 cells stably transfected with the ARE and a green fluorescent protein (GFP) reporter were treated with increasing concentrations of coumarins and compared to positive controls. tert-Butylhydroquinone (TBHQ) and oltipraz increased GFP fluorescence, as did coumarin, limettin, auraptene, imperatorin, and 7,8-benzoflavone, suggesting that they activate the ARE, whereas isopimpinellin did not increase GFP fluorescence. Next, the effects of orally administered coumarins and oltipraz on hepatic GST and NQO1 activities were compared in Nrf2 knockout mice or Nrf2 heterozygous mice exhibiting the wild-type phenotype. Oltipraz, auraptene, imperatorin, isopimpinellin, and auraptene all significantly increased liver cytosolic GST activities in Nrf2 heterozygous mice. This effect was abrogated in Nrf2(-/-) mice dosed with oltipraz, attenuated in mice Nrf2(-/-) mice treated with auraptene and imperatorin, and still significant in Nrf2(-/-) mice treated with isopimpinellin. Of these compounds, only isopimpinellin significantly increased liver cytosolic NQO1 activities, and this effect was not attenuated in Nrf2(-/-) mice. These results strongly suggest that imperatorin and auraptene induce murine liver cytosolic GST activities via the Nrf2/ARE mechanism. Although structurally similar, isopimpinellin did not appear to activate HepG2-ARE-GFP and the Nrf2 knockout mouse study suggests that isopimpinellin may induce GST and NQO1 via additional mechanisms.
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Registered trials
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