ArticleThe AAPS journal2013
Epigenetic modifications of Nrf2 by 3,3'-diindolylmethane in vitro in TRAMP C1 cell line and in vivo TRAMP prostate tumors.
Article in The AAPS journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 94 citations in OpenAlex.
- Histone modifications across cancers: mechanisms, therapy and clinical translation.Molecular cancer · 2026Review
- Investigating the Epigenetic Therapeutic Potential of Natural Compounds in Cancer.International journal of molecular sciences · 2025Review
- 3,3'-Diindolylmethane Improves the Viral Pneumonia Outcomes After Influenza and SARS-CoV-2 Infection in Animal Models.Viruses · 2025Article
- Indole-3-carbinol prevented tumor progression and potentiated PD1ab therapy by upregulating PTEN in colorectal cancer.Discover oncology · 2025Article
- Epigenetic Modifications as Novel Therapeutic Strategies of Cancer Chemoprevention by Phytochemicals.Pharmaceutical research · 2025Review
- The Aryl Hydrocarbon Receptor and Its Crosstalk: A Chemopreventive Target of Naturally Occurring and Modified Phytochemicals.Molecules (Basel, Switzerland) · 2024Review
- Targeted Silencing of NRF2 by rituximab-conjugated nanoparticles increases the sensitivity of chronic lymphoblastic leukemia cells to Cyclophosphamide.Cell communication and signaling : CCS · 2023Article
- Review
- NRF2 Activation by Nitrogen Heterocycles: A Review.Molecules (Basel, Switzerland) · 2023Review
- Synthetic Methodologies and Therapeutic Potential of Indole-3-Carbinol (I3C) and Its Derivatives.Pharmaceuticals (Basel, Switzerland) · 2023Review
- The molecular biology and therapeutic potential of Nrf2 in leukemia.Cancer cell international · 2022Review
- NRF2: A crucial regulator for mitochondrial metabolic shift and prostate cancer progression.Frontiers in physiology · 2022Review
- Epigenetic Therapeutics Targeting NRF2/KEAP1 Signaling in Cancer Oxidative Stress.Frontiers in pharmacology · 2022Review
- Natural Bioactive Compounds Targeting Epigenetic Pathways in Cancer: A Review on Alkaloids, Terpenoids, Quinones, and Isothiocyanates.Nutrients · 2021Review
- Article
- Regulation of Long Non-Coding RNAs by Plant Secondary Metabolites: A Novel Anticancer Therapeutic Approach.Cancers · 2021Review
- NRF2-Related Epigenetic Modifications in Cardiac and Vascular Complications of Diabetes Mellitus.Frontiers in endocrinology · 2021Review
- Indoles Derived From Glucobrassicin: Cancer Chemoprevention by Indole-3-Carbinol and 3,3'-Diindolylmethane.Frontiers in nutrition · 2021Review
- Epigenetic Regulation of NRF2/KEAP1 by Phytochemicals.Antioxidants (Basel, Switzerland) · 2020Review
- Mechanisms Underlying Biological Effects of Cruciferous Glucosinolate-Derived Isothiocyanates/Indoles: A Focus on Metabolic Syndrome.Frontiers in nutrition · 2020Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
3,3'-diindolylmethane (DIM) is currently being investigated in many clinical trials including prostate, breast, and cervical cancers and has been shown to possess anticancer effects in several in vivo and in vitro models. Previously, DIM has been reported to possess cancer chemopreventive effects in prostate carcinogenesis in TRAMP mice; however, the in vivo mechanism is unclear. The present study aims to investigate the in vitro and in vivo epigenetics modulation of DIM in TRAMP-C1 cells and in TRAMP mouse model. In vitro study utilizing TRAMP-C1 cells showed that DIM suppressed DNMT expression and reversed CpG methylation status of Nrf2 resulting in enhanced expression of Nrf2 and Nrf2-target gene NQO1. In vivo study, TRAMP mice fed with DIM-supplemented diet showed much lower incidence of tumorigenesis and metastasis than the untreated control group similar to what was reported previously. DIM increased apoptosis, decreased cell proliferation and enhanced Nrf2 and Nrf2-target gene NQO1 expression in prostate tissues. Importantly, immunohistochemical analysis showed that DIM reduced the global CpG 5-methylcytosine methylation. Focusing on one of the early cancer chemopreventive target gene Nrf2, bisulfite genomic sequencing showed that DIM decreased the methylation status of the first five CpGs of the Nrf2 promoter region, corroborating with the results of in vitro TRAMP-C1 cells. In summary, our current study shows that DIM is a potent cancer chemopreventive agent for prostate cancer and epigenetic modifications of the CpG including Nrf2 could be a potential mechanism by which DIM exerts its chemopreventive effects.
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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.