ArticleToxicology letters2015
Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR.
Article in Toxicology letters, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 46 citations in OpenAlex.
- Aryl hydrocarbon receptor pharmacology-mechanisms, ligands, and therapeutic potential.Pharmacological reviews · 2026Review
- Evaluation ofJournal of dietary supplements · 2026Article
- Unveiling the Multifaceted Pharmacological Actions of Indole-3-Carbinol and Diindolylmethane: A Comprehensive Review.Plants (Basel, Switzerland) · 2025Review
- Pregnenolone 16-Alpha Carbonitrile, an Agonist of Rodent Pregnane X Receptor, Regulates Testosterone Biosynthesis in Rodent Leydig Cells.Journal of xenobiotics · 2024Article
- Diindoles produced from commensal microbiota metabolites function as endogenous CAR/Nr1i3 ligands.Nature communications · 2024Article
- Investigating the Effect of Satureja khuzestanica Essential oil on MDR1 Gene Expression in Leishmania major.Acta parasitologica · 2024Article
- Evaluating Common Ingredients Contained in Dietary Acne Supplements: An Evidence-Based Review.The Journal of clinical and aesthetic dermatology · 2024Article
- Article
- Diverse roles of microbial indole compounds in eukaryotic systems.Biological reviews of the Cambridge Philosophical Society · 2021Review
- Deciphering structural bases of intestinal and hepatic selectivity in targeting pregnane X receptor with indole-based microbial mimics.Bioorganic chemistry · 2021Article
- Correlation of PPM1A Downregulation with CYP3A4 Repression in the Tumor Liver Tissue of Hepatocellular Carcinoma Patients.European journal of drug metabolism and pharmacokinetics · 2020Article
- Belinostat, at Its Clinically Relevant Concentrations, Inhibits Rifampicin-Induced CYP3A4 and MDR1 Gene Expression.Molecular pharmacology · 2019Article
- Drug discovery technologies to identify and characterize modulators of the pregnane X receptor and the constitutive androstane receptor.Drug discovery today · 2019Review
- Drug Transporter Expression and Activity in Human Hepatoma HuH-7 Cells.Pharmaceutics · 2016Article
- An update on the role of intestinal cytochrome P450 enzymes in drug disposition.Acta pharmaceutica Sinica. B · 2016Review
- Chemopreventive properties of 3,3'-diindolylmethane in breast cancer: evidence from experimental and human studies.Nutrition reviews · 2016Review
- Pregnane X Receptor and Cancer: Context-Specificity is Key.Nuclear receptor research · 2016Article
- Article
- 3-(2-Bromoethyl)-indole inhibits the growth of cancer cells and NF-κB activation.Oncology reports · 2015Article
- Mg2+/Mn2+-dependent phosphatase 1A is involved in regulating pregnane X receptor-mediated cytochrome p450 3A4 gene expression.Drug metabolism and disposition: the biological fate of chemicals · 2015Article
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Activation of human pregnane X receptor (hPXR)-regulated expression of cytochrome P450 3A4 (CYP3A4) and multidrug resistance protein 1 (MDR1) plays an important role in mediating adverse drug interactions. Given the common use of natural products as part of adjunct human health behavior, there is a growing concern about natural products for their potential to induce undesired drug interactions through the activation of hPXR-regulated CYP3A4 and MDR1. Here, we studied whether 3,3'-diindolylmethane (DIM), a natural health supplement, could induce hPXR-mediated regulation of CYP3A4 and MDR1 in human hepatocytes and intestinal cells. DIM, at its physiologically relevant concentrations, not only induced hPXR transactivation of CYP3A4 promoter activity but also induced gene expression of CYP3A4 and MDR1. DIM decreased intracellular accumulation of MDR1 substrate rhodamine 123, suggesting that DIM induces the functional expression of MDR1. Pharmacologic inhibition or genetic knockdown of hPXR resulted in attenuation of DIM induced CYP3A4 and MDR1 gene expression, suggesting that DIM induces CYP3A4 and MDR1 in an hPXR-dependent manner. Together, these results support our conclusion that DIM induces hPXR-regulated CYP3A4 and MDR1 gene expression. The inductive effects of DIM on CYP3A4 and MDR1 expression caution the use of DIM in conjunction with other medications metabolized and transported via CYP3A4 and MDR1, respectively.
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