ArticleThe Journal of pharmacology and experimental therapeutics2008
Role of pregnane X receptor in control of all-trans retinoic acid (ATRA) metabolism and its potential contribution to ATRA resistance.
Article in The Journal of pharmacology and experimental therapeutics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 41 citations in OpenAlex.
- Article
- Cellular retinol binding protein-1 inhibits cancer stemness via upregulating WIF1 to suppress Wnt/β-catenin pathway in hepatocellular carcinoma.BMC cancer · 2021Article
- Nuclear Receptors as Multiple Regulators of NLRP3 Inflammasome Function.Frontiers in immunology · 2021Review
- Synergy from gene expression and network mining (SynGeNet) method predicts synergistic drug combinations for diverse melanoma genomic subtypes.NPJ systems biology and applications · 2019Article
- Retinoid-xenobiotic interactions: the Ying and the Yang.Hepatobiliary surgery and nutrition · 2015Review
- Induction of CYP26A1 by metabolites of retinoic acid: evidence that CYP26A1 is an important enzyme in the elimination of active retinoids.Molecular pharmacology · 2015Article
- Role of pregnane X receptor in chemotherapeutic treatment.Cancer chemotherapy and pharmacology · 2014Review
- Expression of the PXR gene in various types of cancer and drug resistance.Oncology letters · 2013Article
- Xenobiotic metabolomics: major impact on the metabolome.Annual review of pharmacology and toxicology · 2012Review
- Nuclear receptor PXR, transcriptional circuits and metabolic relevance.Biochimica et biophysica acta · 2011Review
- Overcoming drug resistance by regulating nuclear receptors.Advanced drug delivery reviews · 2010Review
- Regulation of hepatic ABCC transporters by xenobiotics and in disease states.Drug metabolism reviews · 2010Review
- Altered retinoic acid metabolism in diabetic mouse kidney identified by O isotopic labeling and 2D mass spectrometry.PloS one · 2010Article
- Pregnane X Receptor (PXR) expression in colorectal cancer cells restricts irinotecan chemosensitivity through enhanced SN-38 glucuronidation.Molecular cancer · 2010Article
- The aldo-keto reductase Akr1b7 gene is a common transcriptional target of xenobiotic receptors pregnane X receptor and constitutive androstane receptor.Molecular pharmacology · 2009Article
- Elucidating the 'Jekyll and Hyde' nature of PXR: the case for discovering antagonists or allosteric antagonists.Pharmaceutical research · 2009Review
- Identification of pregnane X receptor ligands using time-resolved fluorescence resonance energy transfer and quantitative high-throughput screening.Assay and drug development technologies · 2009Article
- PXR: a xenobiotic receptor of diverse function implicated in pharmacogenetics.Pharmacogenomics · 2008Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Although all-trans-retinoic acid (ATRA) is an effective treatment for acute promyelocytic leukemia and several solid tumors, its use is limited by resistance due to increased metabolism. The most studied mechanism for ATRA resistance is the autoinduced metabolism regulated by the retinoic acid receptor-CYP26 pathway. However, treatment of cancer is usually not done with a single antineoplastic agent, but with a variety of combined chemotherapy regimens, including several anticancer drugs, and other concomitantly administered supportive drugs. Pregnane X receptor (PXR), an orphan nuclear receptor that functions as a ligand-activated transcription factor, serves as an important xenobiotic sensor regulating metabolism and elimination. Many prescription drugs are PXR ligands, which can activate PXR target genes, including phase I enzyme, phase II enzyme, and transporter genes. The present study was designed to examine the role of PXR in ATRA metabolism. Due to the marked species differences in response to PXR ligands, Pxr-null, wild-type, and PXR-humanized transgenic mouse models were used. In addition to pregnenolone 16alpha-carbonitrile, several clinically relevant PXR ligands (rifampicin and dexamethasone) all increased ATRA metabolism both in vitro and in vivo, which was PXR-dependent, and up-regulation of Cyp3a was the major contributor. Furthermore, induction of the Mdr1a, Mrp3, and Oatp2 genes was also observed. This study suggested that coadministration of PXR ligands can increase ATRA metabolism through activation of the PXR-CYP3A pathway, which might be a mechanism for some form of ATRA resistance. Other PXR target transporters might also be involved.
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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.