ArticleThe Journal of biological chemistry
The STAT3 inhibitor Stattic acts independently of STAT3 to decrease histone acetylation and modulate gene expression.
Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 49 citations in OpenAlex.
- Review
- Role of Janus kinase-signal transducer and activator of transcription signaling pathway in hormonal cancer therapeutic resistance and lineage plasticity.Endocrinology · 2026Review
- Article
- Therapeutic Potential of Polydatin Against Cancer Cachexia by Regulating the STAT3 Signaling Pathway.Nutrients · 2026Article
- PEAK1 promotes prostate cancer progression and docetaxel resistance by mediating the polarization of tumor-associated macrophages.European journal of medical research · 2026Article
- FMRP regulation of STAT3-MYC signaling is critical for adult hippocampal neurogenesis and cognitive flexibility.Cell death and differentiation · 2026Article
- Sodium butyrate alleviates DSS-induced inflammatory bowel disease by inhibiting ferroptosis and modulating ERK/STAT3 signaling and intestinal flora.Annals of medicine · 2025Article
- The Significance of STAT3 in Colonic Diseases: A Comprehensive Study of Pathological Roles and Therapeutic Implications.Cell biochemistry and biophysics · 2025Review
- Exploring the anticancer potential of nitrated N-substituted-4-hydroxy-2-quinolone-3-carboxamides: synthesis, biological assessment, and computational analysis.BMC chemistry · 2025Article
- Fibroblast Activation Protein (FAP)Oncogene · 2025Article
- TMEM71 is crucial for cell proliferation in lower-grade glioma and is linked to unfavorable prognosis.Cancer cell international · 2025Article
- Review
- Unraveling the role of STAT3 in Cancer Cachexia: pathogenic mechanisms and therapeutic opportunities.Frontiers in endocrinology · 2025Review
- Discovery of a 6-Aminobenzo[ACS pharmacology & translational science · 2024Article
- Targeting p97-Npl4 interaction inhibits tumor TNature immunology · 2024Article
- Atg5 deficiency in macrophages protects against kidney fibrosis via the CCR6-CCL20 axis.Cell communication and signaling : CCS · 2024Article
- Potential therapeutic targets of the JAK2/STAT3 signaling pathway in triple-negative breast cancer.Frontiers in oncology · 2024Review
- Feasibility of the inhibitor development for cancer: A systematic approach for drug design.PloS one · 2024Article
- Computational workflow for discovering small molecular binders for shallow binding sites by integrating molecular dynamics simulation, pharmacophore modeling, and machine learning: STAT3 as case study.Journal of computer-aided molecular design · 2023Article
- Visualization of breast cancer-related protein synthesis from the perspective of bibliometric analysis.European journal of medical research · 2023Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Signal transducer and activator of transcription 3 (STAT3) is an important transcription factor involved in many physiological functions including embryonic development and immune responses and is often activated under pathological conditions such as cancer. Strategies to inactivate STAT3 are being pursued as potential anticancer therapies and have led to the identification of Stattic (6-nitrobenzo[b]thiophene-1,1-dioxide) as a "specific" STAT3 inhibitor that is often used to interrogate STAT3-mediated gene expression in vitro and in vivo. Here, we show that Stattic exerts many STAT3-independent effects on cancer cells, calling for reassessment of results previously ascribed to STAT3 functions. Studies of the STAT3-deficient prostate cancer cell line PC-3 (PC3) along with STAT3-proficient breast cancer cell lines (MDA-MB-231, SUM149) revealed that Stattic attenuated histone acetylation and neutralized effects of the histone deacetylase (HDAC) inhibitor romidepsin. In PC3 cells, Stattic alone inhibited gene expression of CCL20 and CCL2, but activated expression of TNFA, CEBPD, SOX2, and MYC. In addition, we found that Stattic promoted autophagy and caused cell death. These data point to profound epigenetic effects of Stattic that are independent of its function as a STAT3 inhibitor. Our results demonstrate that Stattic directly or indirectly reduces histone acetylation and suggest reevaluation of Stattic and related compounds as polypharmacological agents through multipronged cytotoxic effects on cancer cells.
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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.