ArticleThe Journal of biological chemistry2014
Galiellalactone is a direct inhibitor of the transcription factor STAT3 in prostate cancer cells.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 91 citations in OpenAlex.
- Ineffectiveness of immune checkpoint inhibitors in prostate cancer: is it just a question of '-mabs'?The Journal of pathology · 2026Review
- Combination of PARP inhibitor olaparib and a vascular disrupting agent reduces tumor growth in a preclinical model of prostate cancer.Cancer chemotherapy and pharmacology · 2026Article
- Synthesis of 5,5,6-Fused Tricyclic Lactones: Stereocontrol of Three Consecutive Stereocenters.Organic letters · 2026Article
- STAT3 signaling in cancer: mechanisms and targeting therapeutic.Frontiers in immunology · 2026Review
- STAT3 axis in cancer and cancer stem cells: From oncogenesis to targeted therapies.Biochimica et biophysica acta. Reviews on cancer · 2025Review
- Application of Hosomi-Sakurai allylation reaction in total synthesis of biologically active natural products.Frontiers in chemistry · 2025Review
- Heterocyclic Phytochemicals as Anticancer Agents.Current topics in medicinal chemistry · 2025Review
- Article
- Baitouweng decoction suppresses growth of esophageal carcinoma cells through miR-495-3p/BUB1/STAT3 axis.World journal of gastrointestinal oncology · 2024Article
- Unraveling the complexity of STAT3 in cancer: molecular understanding and drug discovery.Journal of experimental & clinical cancer research : CR · 2024Review
- JAK/STAT3 signaling in cardiac fibrosis: a promising therapeutic target.Frontiers in pharmacology · 2024Review
- Eupalinolide J Inhibits Cancer Metastasis by Promoting STAT3 Ubiquitin-Dependent Degradation.Molecules (Basel, Switzerland) · 2023Article
- The JAK-STAT Signaling Pathway in Epilepsy.Current neuropharmacology · 2023Review
- Synthetic and Naturally Occurring Heterocyclic Anticancer Compounds with Multiple Biological Targets.Molecules (Basel, Switzerland) · 2021Review
- The Importance of 6-Aminohexanoic Acid as a Hydrophobic, Flexible Structural Element.International journal of molecular sciences · 2021Review
- Inhibition of STAT3 augments antitumor efficacy of anti-CTLA-4 treatment against prostate cancer.Cancer immunology, immunotherapy : CII · 2021Article
- Trefoil Factor 3 Inhibits Thyroid Cancer Cell Progression Related to IL-6/JAK/STAT3 Signaling Pathway.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Review
- STAT3 inhibition with galiellalactone effectively targets the prostate cancer stem-like cell population.Scientific reports · 2020Article
- CD73 immune checkpoint defines regulatory NK cells within the tumor microenvironment.The Journal of clinical investigation · 2020Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transcription factor STAT3 is constitutively active in several malignancies including castration-resistant prostate cancer and has been identified as a promising therapeutic target. The fungal metabolite galiellalactone, a STAT3 signaling inhibitor, inhibits the growth, both in vitro and in vivo, of prostate cancer cells expressing active STAT3 and induces apoptosis of prostate cancer stem cell-like cells expressing phosphorylated STAT3 (pSTAT3). However, the molecular mechanism of this STAT3-inhibiting effect by galiellalactone has not been clarified. A biotinylated analogue of galiellalactone (GL-biot) was synthesized to be used for identification of galiellalactone target proteins. By adding streptavidin-Sepharose beads to GL-biot-treated DU145 cell lysates, STAT3 was isolated and identified as a target protein. Confocal microscopy revealed GL-biot in both the cytoplasm and the nucleus of DU145 cells treated with GL-biot, appearing to co-localize with STAT3 in the nucleus. Galiellalactone inhibited STAT3 binding to DNA in DU145 cell lysates without affecting phosphorylation status of STAT3. Mass spectrometry analysis of recombinant STAT3 protein pretreated with galiellalactone revealed three modified cysteines (Cys-367, Cys-468, and Cys-542). Here we demonstrate with chemical and molecular pharmacological methods that galiellalactone is a cysteine reactive inhibitor that covalently binds to one or more cysteines in STAT3 and that this leads to inhibition of STAT3 binding to DNA and thus blocks STAT3 signaling without affecting phosphorylation. This further validates galiellalactone as a promising direct STAT3 inhibitor for treatment of castration-resistant prostate cancer.
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