ArticleCellular oncology (Dordrecht, Netherlands)2016
IL6-induced metastasis modulators p-STAT3, MMP-2 and MMP-9 are targets of 3,3'-diindolylmethane in ovarian cancer cells.
Article in Cellular oncology (Dordrecht, Netherlands), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 65 citations in OpenAlex.
- Article
- Senescent cell clearance suppresses post-radiotherapy glioblastoma recurrence via the IL-6/JAK2/STAT3 pathway.Molecular and cellular biochemistry · 2026Article
- 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
- Gammaherpesvirus Infection Stimulates Lung Tumor-Promoting Inflammation.Pathogens (Basel, Switzerland) · 2024Article
- Secreted Soluble Factors from Tumor-Activated Mesenchymal Stromal Cells Confer Platinum Chemoresistance to Ovarian Cancer Cells.International journal of molecular sciences · 2023Article
- Radiobiological effects of wound fluid on breast cancer cell lines and human-derived tumor spheroids in 2D and microfluidic culture.Scientific reports · 2022Article
- Clinicopathological Significance of STAT3 and p-STAT3 among 91 Patients with Adenocarcinoma of the Esophagogastric Junction.Disease markers · 2022Article
- A Novel Orthotopic Liver Cancer Model for Creating a Human-like Tumor Microenvironment.Cancers · 2021Article
- High Levels of the Cleaved Form of Galectin-9 and Osteopontin in the Plasma Are Associated with Inflammatory Markers That Reflect the Severity of COVID-19 Pneumonia.International journal of molecular sciences · 2021Article
- RIPK4 Suppresses the Invasion and Metastasis of Hepatocellular Carcinoma by Inhibiting the Phosphorylation of STAT3.Frontiers in molecular biosciences · 2021Article
- The Role ofMolecules (Basel, Switzerland) · 2020Review
- Activation of STAT3 and STAT5 Signaling in Epithelial Ovarian Cancer Progression: Mechanism and Therapeutic Opportunity.Cancers · 2019Review
- G protein-coupled receptor kinase 2 regulating β2-adrenergic receptor signaling in M2-polarized macrophages contributes to hepatocellular carcinoma progression.OncoTargets and therapy · 2019Article
- Drosophila Jak/STAT Signaling: Regulation and Relevance in Human Cancer and Metastasis.International journal of molecular sciences · 2018Review
- A new promising way of maintenance therapy in advanced ovarian cancer: a comparative clinical study.BMC cancer · 2018Article
- Recent progress in natural dietary non-phenolic bioactives on cancers metastasis.Journal of food and drug analysis · 2018Review
- A heterometallic ruthenium-gold complex displays antiproliferative, antimigratory, and antiangiogenic properties and inhibits metastasis and angiogenesis-associated proteases in renal cancer.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2018Article
- Sex and interleukin-6 are prognostic factors for autoimmune toxicity following treatment with anti-CTLA4 blockade.Journal of translational medicine · 2018Observational
- Blocking interleukin-6 signaling inhibits cell viability/proliferation, glycolysis, and colony forming activity of human medulloblastoma cells.International journal of oncology · 2018Article
- FPR1 mediates the tumorigenicity of human cervical cancer cells.Cancer management and research · 2018Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeOvarian cancer is a highly lethal gynecological malignancy for which the overall prognosis has remained poor over the past few decades. Interleukin (IL6) has been found to be a major contributor to the initiation and progression of ovarian cancer. This cytokine exerts its activity through activation of several signaling pathways, in particular the signal transducer and activator of transcription (STAT3) pathway. Here, we aimed at investigating the capacity of a natural dietary compound found in cruciferous vegetables, i.e., 3,3'-diindolylmethane (DIM), to target the metastatic phenotype of ovarian cancer cells through functional p-STAT3.
methodsThe human ovarian carcinoma-derived cell lines SKOV3 and A2780 were treated with IL6 and/or DIM and subjected to in vitro proliferation, adhesion, migration and invasion assays to assess the anti-metastatic and anti-IL6 effects of DIM, as well as to assess gene expression alterations before and after shRNA-mediated STAT3 silencing.
resultsWe found that DIM inhibits IL6-mediated increases in ovarian cancer cell adhesion, migration and invasion. These results were corroborated by shRNA-mediated STAT3 silencing. Through Western blot and ELISA analyses direct evidence was provided for the capacity of DIM to inhibit ovarian cancer cell adhesion, migration and invasion, which was found to be associated with down-regulation of the matrix metalloproteinases MMP-2 and MMP-9.
conclusionsFrom our data we conclude that DIM exhibits an anti-IL6-like activity by inhibiting p-STAT3 enhanced ovarian cancer cell proliferation and in vitro metastasis-associated events, i.e., adhesion, migration and invasion. Most significantly, MMP-2 and MMP-9, which are known to promote and enhance metastasis, were found to act as targets of DIM. This anti-IL6-like property of DIM may pave the way for the development of novel ovarian cancer preventive and/or therapeutic strategies.
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