ArticleCancer research2008
Modulation of orphan nuclear receptor Nur77-mediated apoptotic pathway by acetylshikonin and analogues.
Article in Cancer research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 75 citations in OpenAlex.
- Targeting the nuclear orphan receptor NR4A1: a key target in lung cancer progression and therapeutic resistance.Frontiers in oncology · 2025Review
- Exploring the nexus of nuclear receptors in hematological malignancies.Cellular and molecular life sciences : CMLS · 2024Review
- Natural compounds targeting nuclear receptors for effective cancer therapy.Cancer metastasis reviews · 2023Review
- Nur77 Serves as a Potential Prognostic Biomarker That Correlates with Immune Infiltration and May Act as a Good Target for Prostate adenocarcinoma.Molecules (Basel, Switzerland) · 2023Article
- Inhibition of Nur77 expression and translocation by compound B6 reduces ER stress and alleviates cigarette smoke-induced inflammation and injury in bronchial epithelial cells.Frontiers in pharmacology · 2023Article
- Article
- Synthesis and Biological Evaluation of 1-(2-(6-Methoxynaphthalen-2-yl)-6-methylnicotinoyl)-4-Substituted Semicarbazides/Thiosemicarbazides as Anti-Tumor Nur77 Modulators.Molecules (Basel, Switzerland) · 2022Article
- Quercetin Mitigates Methamphetamine-Induced Anxiety-Like Behavior Through Ameliorating Mitochondrial Dysfunction and Neuroinflammation.Frontiers in molecular neuroscience · 2022Article
- The Paradoxical Roles of Orphan Nuclear Receptor 4A (NR4A) in Cancer.Molecular cancer research : MCR · 2021Review
- Pharmacology, toxicity and pharmacokinetics of acetylshikonin: a review.Pharmaceutical biology · 2020Review
- Article
- Sulindac-derived retinoid X receptor-α modulator attenuates atherosclerotic plaque progression and destabilization in ApoEBritish journal of pharmacology · 2019Article
- Key Functions and Therapeutic Prospects of Nur77 in Inflammation Related Lung DiseasesThe American journal of pathology · 2019Review
- Broad blocking of MDR efflux pumps by acetylshikonin and acetoxyisovalerylshikonin to generate hypersensitive phenotype of malignant carcinoma cells.Scientific reports · 2018Article
- Modulation of the Nur77-Bcl-2 apoptotic pathway by p38α MAPK.Oncotarget · 2017Article
- Targeting to the non-genomic activity of retinoic acid receptor-gamma by acacetin in hepatocellular carcinoma.Scientific reports · 2017Article
- Article
- Review
- Nuclear receptor 4A (NR4A) family - orphans no more.The Journal of steroid biochemistry and molecular biology · 2016Article
- Induction of Nur77-dependent apoptotic pathway by a coumarin derivative through activation of JNK and p38 MAPK.Carcinogenesis · 2014Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Shikonin derivatives, which are the active components of the medicinal plant Lithospermum erythrorhizon, exhibit many biological effects including apoptosis induction through undefined mechanisms. We recently discovered that orphan nuclear receptor Nur77 migrates from the nucleus to the mitochondria, where it binds to Bcl-2 to induce apoptosis. Here, we report that certain shikonin derivatives could modulate the Nur77/Bcl-2 apoptotic pathway by increasing levels of Nur77 protein and promoting its mitochondrial targeting in cancer cells. Structural modification of acetylshikonin resulted in the identification of a derivative 5,8-diacetoxyl-6-(1'-acetoxyl-4'-methyl-3'-pentenyl)-1,4-naphthaquinones (SK07) that exhibited improved efficacy and specificity in activating the pathway. Unlike other Nur77 modulators, shikonins increased the levels of Nur77 protein through their posttranscriptional regulation. The apoptotic effect of SK07 was impaired in Nur77 knockout cells and suppressed by cotreatment with leptomycin B that inhibited Nur77 cytoplasmic localization. Furthermore, SK07 induced apoptosis in cells expressing the COOH-terminal half of Nur77 protein but not its NH(2)-terminal region. Our data also showed that SK07-induced apoptosis was associated with a Bcl-2 conformational change and Bax activation. Together, our results show that certain shikonin derivatives act as modulators of the Nur77-mediated apoptotic pathway and identify a new shikonin-based lead that targets Nur77 for apoptosis induction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.