ArticleProceedings of the National Academy of Sciences of the United States of America2013
DIM (3,3'-diindolylmethane) confers protection against ionizing radiation by a unique mechanism.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 100 citations in OpenAlex.
- BRCA1 mRNA levels following a 4-6-week intervention with oral 3,3'-diindolylmethane.British journal of cancer · 2014Trial
- Nutritional, Therapeutic, and Functional Food Perspectives of Kale (Molecules (Basel, Switzerland) · 2025Review
- Integrated Lipidomics and Network Pharmacology Reveal the AMPK-Mediated Therapeutic Mechanism of 3,3'-Diindolylmethane in Hepatic Lipid Metabolism.Antioxidants (Basel, Switzerland) · 2025Article
- Cruciferous Vegetables, Bioactive Metabolites, and Microbiome for Breast Cancer Prevention.Annual review of nutrition · 2025Review
- Unveiling the Multifaceted Pharmacological Actions of Indole-3-Carbinol and Diindolylmethane: A Comprehensive Review.Plants (Basel, Switzerland) · 2025Review
- Article
- Topically applied fullerenols protect against radiation dermatitis by scavenging reactive oxygen species.Discover nano · 2023Article
- Connection between Radiation-Regulating Functions of Natural Products and miRNAs Targeting Radiomodulation and Exosome Biogenesis.International journal of molecular sciences · 2023Review
- Molecular portraits of cell cycle checkpoint kinases in cancer evolution, progression, and treatment responsiveness.Science advances · 2023Article
- A microbiota and dietary metabolite integrates DNA repair and cell death to regulate embryo viability and aneuploidy during aging.Science advances · 2023Article
- Synthetic Methodologies and Therapeutic Potential of Indole-3-Carbinol (I3C) and Its Derivatives.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Indole-3-carbinol in vitro antiviral activity against SARS-Cov-2 virus and in vivo toxicity.Cell death discovery · 2022Article
- D-galactose protects the intestine from ionizing radiation-induced injury by altering the gut microbiome.Journal of radiation research · 2022Article
- Atomically precise silver clusterzymes protect mice from radiation damages.Journal of nanobiotechnology · 2021Article
- Antioxidative Stress: Inhibiting Reactive Oxygen Species Production as a Cause of Radioresistance and Chemoresistance.Oxidative medicine and cellular longevity · 2021Review
- Indoles Derived From Glucobrassicin: Cancer Chemoprevention by Indole-3-Carbinol and 3,3'-Diindolylmethane.Frontiers in nutrition · 2021Review
- Effect of 3,3'-Diindolylmethane on Pulmonary Injury Following Thoracic Irradiation in CBA Mice.Health physics · 2020Article
- Radioprotection and Radiomitigation: From the Bench to Clinical Practice.Biomedicines · 2020Review
- CLPTM1L induces estrogen receptor β signaling-mediated radioresistance in non-small cell lung cancer cells.Cell communication and signaling : CCS · 2020Article
- Genome-Protecting Compounds as Potential Geroprotectors.International journal of molecular sciences · 2020Review
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
DIM (3,3'-diindolylmethane), a small molecule compound, is a proposed cancer preventive agent that can be safely administered to humans in repeated doses. We report that administration of DIM in a multidose schedule protected rodents against lethal doses of total body irradiation up to 13 Gy, whether DIM dosing was initiated before or up to 24 h after radiation. Physiologic submicromolar concentrations of DIM protected cultured cells against radiation by a unique mechanism: DIM caused rapid activation of ataxia-telangiectasia mutated (ATM), a nuclear kinase that regulates responses to DNA damage (DDR) and oxidative stress. Subsequently, multiple ATM substrates were phosphorylated, suggesting that DIM induces an ATM-dependent DDR-like response, and DIM enhanced radiation-induced ATM signaling and NF-κB activation. DIM also caused activation of ATM in rodent tissues. Activation of ATM by DIM may be due, in part, to inhibition of protein phosphatase 2A, an upstream regulator of ATM. In contrast, DIM did not protect human breast cancer xenograft tumors against radiation under the conditions tested. In tumors, ATM was constitutively phosphorylated and was not further stimulated by radiation and/or DIM. Our findings suggest that DIM is a potent radioprotector and mitigator that functions by stimulating an ATM-driven DDR-like response and NF-κB survival signaling.
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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.