ArticleInternational journal of molecular sciences2020
Chemopreventive Agent 3,3'-Diindolylmethane Inhibits MDM2 in Colorectal Cancer Cells.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 24 citations in OpenAlex.
- 3,3'-Diindolylmethane blocks the dissemination of gastric cancer cells in the peritoneal cavity through the MFGE8-MAPK/ERK signaling pathway.Cancer cell international · 2025Article
- The Therapeutic Potential of Spirooxindoles in Cancer: A Focus on p53-MDM2 Modulation.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Mitigating the Oncogenic Roles of miR-629-5p and miR-660-5p Through Direct Binding by Two Potential Drug Targets for Colorectal Cancer Prevention.International journal of preventive medicine · 2025Article
- MDM2: current research status and prospects of tumor treatment.Cancer cell international · 2024Review
- Glucosinolates in cancer prevention and treatment: experimental and clinical evidence.Medical oncology (Northwood, London, England) · 2023Review
- 3,3'-Diindolylmethane and indole-3-carbinol: potential therapeutic molecules for cancer chemoprevention and treatment via regulating cellular signaling pathways.Cancer cell international · 2023Review
- The Effect of Dietary Factors on Cancer.International journal of molecular sciences · 2023Article
- 3,3'-Diindolylmethane Enhances Fluorouracil Sensitivity via Inhibition of Pyrimidine Metabolism in Colorectal Cancer.Metabolites · 2022Article
- Regulatory Effects of Apatinib in Combination with Piperine on MDM-2 Gene Expression, Glutathione Peroxidase Activity and Nitric Oxide level as Mechanisms of Cytotoxicity in Colorectal Cancer Cells.Advanced pharmaceutical bulletin · 2022Article
- Article
- Indoles Derived From Glucobrassicin: Cancer Chemoprevention by Indole-3-Carbinol and 3,3'-Diindolylmethane.Frontiers in nutrition · 2021Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
3,3'-Diindolylmethane (DIM) is a naturally derived chemopreventive compound. It comes from glucobrassicin, an indole glucosinolate enriched in cruciferous vegetables, and is formed in the acidic environment of the stomach after ingestion. Mouse double minute 2 homolog (MDM2) is an important, multi-functional oncogenic protein and it has been well recognized for its negative regulation of the tumor suppressor protein p53. We discovered a novel mechanism of action of DIM, that it directly inhibits MDM2 in multiple colorectal cancer (CRC) cell lines. Treatment with DIM decreased MDM2 at messenger RNA (mRNA) and protein levels, inhibited cancer cell proliferation, and induced cell cycle arrest and apoptosis. DIM-induced decrease of MDM2 is p53-independent and is partly mediated by proteasome degradation of MDM2, as blocking of the proteasome activity reversed MDM2 protein inhibition. Overexpression of MDM2 blocked DIM's effects in growth suppression and apoptosis induction. When combined with imidazoline MDM2 inhibitors (Nutlin-3a and Idasanutlin/RG-7388), synergism was observed in cancer cell growth inhibition. In summary, our data support a new mechanism of action for DIM in direct inhibition of MDM2. The identification of MDM2 as a novel DIM target may help develop a new strategy in CRC prevention.
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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.