ArticleBMC medicine2012
Diindolylmethane suppresses ovarian cancer growth and potentiates the effect of cisplatin in tumor mouse model by targeting signal transducer and activator of transcription 3 (STAT3).
Article in BMC medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 59 citations in OpenAlex.
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- ITGB4 up-regulated by STAT3 reduces the sensitivity of bladder cancer to cisplatin by suppressing p53.British journal of cancer · 2026Article
- 3,3'-Diindolylmethane Improves the Viral Pneumonia Outcomes After Influenza and SARS-CoV-2 Infection in Animal Models.Viruses · 2025Article
- Interleukin-6 Modulation in Ovarian Cancer Necessitates a Targeted Strategy: From the Approved to Emerging Therapies.Cancers · 2024Review
- Selumetinib overcomes gefitinib primary and acquired resistance by regulating MIG6/STAT3 in NSCLC.Archives of pharmacal research · 2023Article
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- A novel small molecule LLL12B inhibits STAT3 signaling and sensitizes ovarian cancer cell to paclitaxel and cisplatin.PloS one · 2021Article
- The Capacity of the Ovarian Cancer Tumor Microenvironment to Integrate Inflammation Signaling Conveys a Shorter Disease-free Interval.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- Synergistic Anti-Tumor Activity by Targeting Multiple Signaling Pathways in Ovarian Cancer.Cancers · 2020Article
- STAT3 signaling in ovarian cancer: a potential therapeutic target.Journal of Cancer · 2020Review
- 3,3'-Diindolylmethane enhances apoptosis in docetaxel-treated breast cancer cells by generation of reactive oxygen species.Pharmaceutical biology · 2018Article
- Pterostilbene Suppresses Ovarian Cancer Growth via Induction of Apoptosis and Blockade of Cell Cycle Progression Involving Inhibition of the STAT3 Pathway.International journal of molecular sciences · 2018Article
- Ruxolitinib synergistically enhances the anti-tumor activity of paclitaxel in human ovarian cancer.Oncotarget · 2018Article
- Stat3 as a potential therapeutic target for rheumatoid arthritis.Scientific reports · 2017Article
- Targeting phosphorylation of STAT3 delays tumor growth in HPV-negative anal squamous cell carcinoma mouse model.Scientific reports · 2017Article
- Article
- Preclinical optimization of a broad-spectrum anti-bladder cancer tri-drug regimen via the Feedback System Control (FSC) platform.Scientific reports · 2015Article
- 3,3'-Diindolylmethane: A Promising Sensitizer of γ-Irradiation.BioMed research international · 2015Article
- Article
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2 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundSignal transducer and activator of transcription 3 (STAT3) is activated in majority of ovarian tumors and confers resistance to cisplatin treatment in patients with ovarian cancer. We have reported previously that diindolylmethane (DIM) inhibits the growth of ovarian cancer cells. However, to date the exact mechanism by which DIM induces growth suppressive effects has not been clear. In this report the mode of action of DIM is investigated.
methodsSix human ovarian cancer cell lines and an ovarian tumor xenograft animal model were used to study the effect of diindolylmethane alone or in combination with cisplatin.
resultsDiindolylmethane treatment induced apoptosis in all six ovarian cancer cell lines. Phosphorylation of STAT3 at Tyr-705 and Ser-727 was reduced by DIM in a concentration-dependent manner. In addition, diindolylmethane treatment inhibited nuclear translocation, DNA binding, and transcriptional activity of STAT3. Interleukin (IL)-6-induced phosphorylation of STAT3 at Tyr-705 was significantly blocked by DIM. Overexpression of STAT3 by gene transfection blocked DIM-induced apoptosis. In addition, DIM treatment reduced the levels of IL-6 in ovarian cancer cells and in the tumors. DIM treatment also inhibited cell invasion and angiogenesis by suppressing hypoxia-inducible factor 1α (HIF-1α) and vascular epithelial growth factor (VEGF). Importantly, diindolylmethane treatment potentiated the effects of cisplatin in SKOV-3 cells by targeting STAT3. Oral administration of 3 mg diindolylmethane per day and subsequent administration of cisplatin substantially inhibited in vivo tumor growth. Western blotting analysis of tumor lysates indicated increased apoptosis and reduced STAT3 activation.
conclusionsThese findings provide a rationale for further clinical investigation of DIM alone or in combination for chemoprevention and/or chemotherapy of ovarian cancer.
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