ArticleMolecules (Basel, Switzerland)2018
Parthenolide Inhibits STAT3 Signaling by Covalently Targeting Janus Kinases.
Article in Molecules (Basel, Switzerland), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 58 citations in OpenAlex.
- Identification of human MLKL Cys184 and HSPBP1 Cys201 as novel cellular targets for necroptosis.Cell death & disease · 2026Article
- Wood smoke particles elicit events associated with adverse effects in human lung epithelial cells.Frontiers in toxicology · 2026Article
- Purification, Fluorescent Labeling, and Detyrosination of Mammalian Cell Tubulin for Biochemical Assays.Cytoskeleton (Hoboken, N.J.) · 2025Article
- Regulation of the tumor microenvironment by Traditional Chinese Medicine: current progress and future perspectives in oncology.American journal of translational research · 2025Review
- Inhibition of STAT3-NF-κB pathway facilitates SSPH I-induced ferroptosis in HepG2 cells.Medical oncology (Northwood, London, England) · 2024Article
- Terpenoid-Mediated Targeting of STAT3 Signaling in Cancer: An Overview of Preclinical Studies.Biomolecules · 2024Review
- Investigation of targets and anticancer mechanisms of covalently acting natural products by functional proteomics.Acta pharmacologica Sinica · 2023Article
- Untargeted lipidomic analysis and network pharmacology for parthenolide treated papillary thyroid carcinoma cells.BMC complementary medicine and therapies · 2023Article
- Plants as a Source of Anticancer Agents: From Bench to Bedside.Molecules (Basel, Switzerland) · 2022Review
- Article
- Parthenolide and Its Soluble Analogues: Multitasking Compounds with Antitumor Properties.Biomedicines · 2022Review
- Anti-Inflammatory and Immunoregulatory Action of Sesquiterpene Lactones.Molecules (Basel, Switzerland) · 2022Review
- The Emerging Potential of Parthenolide Nanoformulations in Tumor Therapy.Drug design, development and therapy · 2022Review
- Sesquiterpene Lactones and Cancer: New Insight into Antitumor and Anti-inflammatory Effects of Parthenolide-Derived Dimethylaminomicheliolide and Micheliolide.Computational and mathematical methods in medicine · 2022Review
- JAK2/STAT3‑mediated dose‑dependent cytostatic and cytotoxic effects of sesquiterpene lactones fromOncology reports · 2022Article
- Disrupting interferon-alpha and NF-kappaB crosstalk suppresses IFITM1 expression attenuating triple-negative breast cancer progression.Cancer letters · 2021Article
- Inhibitory effects of cynaropicrin and related sesquiterpene lactones from leaves of artichoke (Cynara scolymus L.) on induction of iNOS in RAW264.7 cells and its high-affinity proteins.Journal of natural medicines · 2021Article
- Parthenolide Destabilizes Microtubules by Covalently Modifying Tubulin.Current biology : CB · 2021Article
- Natural and Nature-Derived Products Targeting Human Coronaviruses.Molecules (Basel, Switzerland) · 2021Review
- Parthenolide inhibits the growth of non-small cell lung cancer by targeting epidermal growth factor receptor.Cancer cell international · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant activations of the STAT3 (signal transducer and activator of transcription 3) signaling pathway are associated with cancer and inflammatory diseases. Three of the four Janus kinases, JAK1, JAK2, and Tyk2, are the major upstream kinases of STAT3 in responses to cytokine stimulations. Among them, JAK2 is the key kinase in the IL-6-induced STAT3 phosphorylation. Here we report the mechanisms of a natural compound parthenolide from the medicinal herb Feverfew in regulating the JAK/STAT3 signaling. We found that parthenolide was a potent inhibitor of JAKs. It covalently modified the Cys178, Cys243, Cys335, and Cys480 of JAK2 and suppressed its kinase activity. It also interacted with other JAKs in a similar fashion. The binding of parthenolide to JAKs was selective. It preferentially bound to the JAKs, but not to the abundant proteins, such as tubulin and actin. Parthenolide also induced reactive oxygen species (ROS), but the increased ROS did not seem to contribute to the inhibition of JAK/STAT3 signaling. Furthermore, parthenolide inhibited the IL-6-induced cancer cell migration and preferentially inhibited the growth of cancer cells that had constitutively activated STAT3. Our study suggests a novel strategy to inactivate JAKs and provides a promising anti-inflammation and anticancer drug candidate.
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