ArticleHepatology (Baltimore, Md.)2011
Enrichment of Nur77 mediated by retinoic acid receptor β leads to apoptosis of human hepatocellular carcinoma cells induced by fenretinide and histone deacetylase inhibitors.
Article in Hepatology (Baltimore, Md.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- Fenretinide in cancer therapy and chemoprevention: past, present and future.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- Mechanism and application of HDAC inhibitors in the treatment of hepatocellular carcinoma.Journal of molecular medicine (Berlin, Germany) · 2025Review
- A pan-cancer analysis of homeobox family: expression characteristics and latent significance in prognosis and immune microenvironment.Frontiers in oncology · 2025Article
- Retinoids in the Pathogenesis and Treatment of Liver Diseases.Nutrients · 2022Review
- NR4A1 counteracts JNK activation incurred by ER stress or ROS in pancreatic β-cells for protection.Journal of cellular and molecular medicine · 2020Article
- Molecular mechanism of nur77 gene expression and downstream target genes in the early stage of forskolin-induced differentiation in PC12 cells.Scientific reports · 2020Article
- Nur77-activated lncRNA WFDC21P attenuates hepatocarcinogenesis via modulating glycolysis.Oncogene · 2020Article
- RARβ acts as both an upstream regulator and downstream effector of miR-22, which epigenetically regulates NUR77 to induce apoptosis of colon cancer cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Review
- Hepatic inflammation caused by dysregulated bile acid synthesis is reversible by butyrate supplementation.The Journal of pathology · 2017Article
- Nur77 suppresses hepatocellular carcinoma via switching glucose metabolism toward gluconeogenesis through attenuating phosphoenolpyruvate carboxykinase sumoylation.Nature communications · 2017Article
- LncRNA-uc002mbe.2 Interacting with hnRNPA2B1 Mediates AKT Deactivation and p21 Up-Regulation Induced by Trichostatin in Liver Cancer Cells.Frontiers in pharmacology · 2017Article
- The antitumor effect of TIG3 in liver cancer cells is involved in ERK1/2 inhibition.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Nur77-deficiency in bone marrow-derived macrophages modulates inflammatory responses, extracellular matrix homeostasis, phagocytosis and tolerance.BMC genomics · 2016Article
- Retinoic acid receptor beta and angiopoietin-like protein 1 are involved in the regulation of human androgen biosynthesis.Scientific reports · 2015Article
- Bile acids regulate nuclear receptor (Nur77) expression and intracellular location to control proliferation and apoptosis.Molecular cancer research : MCR · 2015Article
- Accelerated partial hepatectomy-induced liver cell proliferation is associated with liver injury in Nur77 knockout mice.The American journal of pathology · 2014Article
- Inhibition of c-Jun N-terminal kinase ameliorates early brain injury after subarachnoid hemorrhage through inhibition of a Nur77 dependent apoptosis pathway.Neurochemical research · 2014Article
- PKA/Smurf1 signaling-mediated stabilization of Nur77 is required for anticancer drug cisplatin-induced apoptosis.Oncogene · 2014Article
- Combination of fenretinide and selenite inhibits proliferation and induces apoptosis in ovarian cancer cells.International journal of molecular sciences · 2013Article
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
Abstract
unlabelledThe synthetic retinoid fenretinide is one of the most promising clinically tested retinoids. Previously, we have shown that fenretinide induces apoptosis of Huh7 cells, but HepG2 cells are relatively resistant to fenretinide-induced apoptosis. This study examines the interactive role of fenretinide and histone deacetylase inhibitors (HDACi) in inducing apoptosis of human hepatocellular carcinoma (HCC) cells and the underlying mechanism. Trichostatin A and scriptaid can either enhance fenretinide-induced apoptosis in the fenretinide sensitive HCC cells (Huh7 and Hep3B) or sensitize the fenretinide resistant cells (HepG2) to become sensitive to the apoptotic effect of fenretinide in a cancer cell-specific manner. The sensitivity of cells to fenretinide-induced apoptosis was not associated with reactive oxygen species production nor with antioxidant gene expression. However, the level of retinoic acid receptor β (RARβ) and Nur77 (NR4A1) was important for inducing apoptosis. Upon fenretinide and HDACi treatment, the expression of RARβ and Nur77 were induced and colocalized in the cytosol. The induction of Nur77 protein level, but not the messenger RNA level, was RARβ-dependent. In addition, RARβ interacted with Nur77. Nur77 was essential for fenretinide-induced and HDACi-induced apoptosis of Huh7 cells. Induction of the expression, the interaction, and the nuclear export of RARβ and Nur77 mediate fenretinide-induced and HDACi-induced apoptosis.
conclusionOur findings suggest that targeting Nur77 and RARβ simultaneously provides an effective way to induce HCC cell death.
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