ArticlePloS one2015
Effects of RXR Agonists on Cell Proliferation/Apoptosis and ACTH Secretion/Pomc Expression.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- A Narrative Overview of Retinoid X Receptor Inhibitors in Chronic Disease Management.Current drug research reviews · 2025Review
- Retinoid X Receptor agonists as selective modulators of the immune system for the treatment of cancer.Pharmacology & therapeutics · 2023Review
- International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023.Pharmacological reviews · 2023Review
- Article
- Dual effects of 9-cis retinoic acid on ACTH-dependent hyperplastic adrenal tissues.Scientific reports · 2021Article
- Targeting the TR4 nuclear receptor with antagonist bexarotene can suppress the proopiomelanocortin signalling in AtT-20 cells.Journal of cellular and molecular medicine · 2021Article
- Computational Drug Repositioning and Experimental Validation of Ivermectin in Treatment of Gastric Cancer.Frontiers in pharmacology · 2021Article
- Nuclear Receptors as Regulators of Pituitary Corticotroph Pro-Opiomelanocortin Transcription.Cells · 2020Review
- Stress as an immunomodulator: liver X receptors maybe the answer.Inflammopharmacology · 2019Review
- Heme oxygenase-1 protects airway epithelium against apoptosis by targeting the proinflammatory NLRP3-RXR axis in asthma.The Journal of biological chemistry · 2018Article
- Gene expression profiling in human corticotroph tumours reveals distinct, neuroendocrine profiles.Journal of neuroendocrinology · 2018Article
- Inhibitory Effects of a Novel PPAR-PPAR research · 2018Article
- Molecular mechanisms of apoptosis in hepatocellular carcinoma cells induced by ethanol extracts ofWorld journal of gastroenterology · 2017Article
- Article
- Suppressive effects of RXR agonist PA024 on adrenal CYP11B2 expression, aldosterone secretion and blood pressure.PloS one · 2017Article
- Combined Central Hypothyroidism and Adrenal Insufficiency Associated with Retinoic Acid Therapy for Cutaneous T-Cell Lymphoma.AACE clinical case reportsArticle
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Various retinoid X receptor (RXR) agonists have recently been developed, and some of them have shown anti-tumor effects both in vivo and in vitro. However, there has been no report showing the effects of RXR agonists on Cushing's disease, which is caused by excessive ACTH secretion in a corticotroph tumor of the pituitary gland. Therefore, we examined the effects of synthetic RXR pan-agonists HX630 and PA024 on the proliferation, apoptosis, ACTH secretion, and pro-opiomelanocortin (Pomc) gene expression of murine pituitary corticotroph tumor AtT20 cells. We demonstrated that both RXR agonists induced apoptosis dose-dependently in AtT20 cells, and inhibited their proliferation at their higher doses. Microarray analysis identified a significant gene network associated with caspase 3 induced by high dose HX630. On the other hand, HX630, but not PA024, inhibited Pomc transcription, Pomc mRNA expression, and ACTH secretion dose-dependently. Furthermore, we provide new evidence that HX630 negatively regulates the Pomc promoter activity at the transcriptional level due to the suppression of the transcription factor Nur77 and Nurr1 mRNA expression and the reduction of Nur77/Nurr1 heterodimer recruiting to the Pomc promoter region. We also demonstrated that the HX630-mediated suppression of the Pomc gene expression was exerted via RXRα. Furthermore, HX630 inhibited tumor growth and decreased Pomc mRNA expression in corticotroph tumor cells in female nude mice in vivo. Thus, these results indicate that RXR agonists, especially HX630, could be a new therapeutic candidate for Cushing's disease.
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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.