ArticleCarcinogenesis2014
Induction of Nur77-dependent apoptotic pathway by a coumarin derivative through activation of JNK and p38 MAPK.
Article in Carcinogenesis, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 45 citations in OpenAlex.
- Pituitary adenylate cyclase-activating polypeptide (PACAP) promotes regeneration of corneal epithelial cells possibly via the NR4A1 signaling pathway.Scientific reports · 2026Article
- The subcellular localization-dependent dual role of NR4A1 in renal fibrosis: mechanisms and therapeutic perspectives.Frontiers in pharmacology · 2026Review
- Targeting the nuclear orphan receptor NR4A1: a key target in lung cancer progression and therapeutic resistance.Frontiers in oncology · 2025Review
- Coumarins in the tumor-immune application: from molecular mechanisms to therapeutic innovations.Frontiers in immunology · 2025Review
- Functional Changes Associated With the Subcellular Localization of the Nuclear Receptor NR4A1.Biochemistry research international · 2025Review
- Phase separation of Nur77 mediates XS561-induced apoptosis by promoting the formation of Nur77/Bcl-2 condensates.Acta pharmaceutica Sinica. B · 2024Article
- Methoxyfuranocoumarins of Natural Origin-Updating Biological Activity Research and Searching for New Directions-A Review.Current issues in molecular biology · 2024Review
- Downregulation of complement factor H attenuates the stemness of MDA‑MB‑231 breast cancer cells via modulation of the ERK and p38 signaling pathways.Oncology letters · 2023Article
- Nr4a1 promotes renal interstitial fibrosis by regulating the p38 MAPK phosphorylation.Molecular medicine (Cambridge, Mass.) · 2023Article
- 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
- Venlafaxine, an anti-depressant drug, induces apoptosis in MV3 human melanoma cells through JNK1/2-Nur77 signaling pathway.Frontiers in pharmacology · 2022Article
- Ethyl Acetate Fraction ofEvidence-based complementary and alternative medicine : eCAM · 2022Article
- The Paradoxical Roles of Orphan Nuclear Receptor 4A (NR4A) in Cancer.Molecular cancer research : MCR · 2021Review
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- Lnc-NA inhibits proliferation and metastasis in endometrioid endometrial carcinoma through regulation of NR4A1.Journal of cellular and molecular medicine · 2019Article
- TGFβ-Induced Lung Cancer Cell Migration Is NR4A1-Dependent.Molecular cancer research : MCR · 2018Article
- The E3 ubiquitin ligase Trim13 regulates Nur77 stability via casein kinase 2α.Scientific reports · 2018Article
- New Drug Candidate Targeting the 4A1 Orphan Nuclear Receptor for Medullary Thyroid Cancer Therapy.Molecules (Basel, Switzerland) · 2018Article
- Human Dental Pulp Stem Cells Are More Effective Than Human Bone Marrow-Derived Mesenchymal Stem Cells in Cerebral Ischemic Injury.Cell transplantation · 2017Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Coumarins are plant-derived natural products with a broad range of known pharmacological activities including anticancer effects. However, the molecular mechanisms by which this class of promising compounds exerts their anticancer effects remain largely unknown. We report here that a furanocoumarin named apaensin could effectively induce apoptosis of cancer cells through its activation of Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK). Apoptosis induction by apaensin in cancer cells was suppressed by chemical inhibitors of JNK and p38 MAPK. Inhibition of the expression of orphan nuclear receptor Nur77 by small interfering RNA (siRNA) approach also abrogated the death effect of apaensin. Molecular analysis demonstrated that JNK activation was required for the nuclear export of Nur77, a known apoptotic event in cancer cells. Although p38 MAPK activation was not involved in Nur77 nuclear export, it was essential for Nur77 mitochondrial targeting through induction of Nur77 interaction with Bcl-2, which is also known to convert Bcl-2 from an antiapoptotic to a proapoptotic molecule. Together, our results identify a new natural product that targets orphan nuclear receptor Nur77 through its unique activation of JNK and p38 MAPK and provide insight into the complex regulation of the Nur77-Bcl-2 apoptotic pathway.
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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.