ArticleBritish journal of cancer2021
Acetyl-bufalin shows potent efficacy against non-small-cell lung cancer by targeting the CDK9/STAT3 signalling pathway.
Article in British journal of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 62 citations in OpenAlex.
- TRMT6-Mediated mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Bufalin targets E2F2 to transcriptionally inhibit LINC01410 and suppress Wnt/β-catenin signaling in esophageal squamous cell carcinoma.NPJ precision oncology · 2026Article
- Ganoderic Acids Alleviate Neuroinflammation by Targeting Myeloid Differentiation Factor 2 for Ischemic Stroke Therapy.Exploration (Beijing, China) · 2026Article
- Green tea catechins and prostate cancer: mechanisms, clinical evidence, and safety: a narrative review.BMC cancer · 2026Review
- Integrating Biosensors in Phytochemical Research: Challenges and Breakthroughs.Recent patents on biotechnology · 2026Review
- Bufalin: a potential drug for regulating EGFR-TKIs resistance in lung cancer via the EGFR-PI3K/Akt-mTOR signaling.Translational cancer research · 2025Article
- Targeting steroid receptor coactivators for the treatment of benign female reproductive disorders.Endocrine connections · 2025Review
- Bruceine D inhibits hepatocellular carcinoma by regulating the STAT3 signaling pathway through HSP70.European journal of medical research · 2025Article
- Article
- Self-assembly of multi-arm star PEG containing TXA9 into nanoparticle for the efficient chemotherapy of NSCLC.Drug delivery and translational research · 2025Article
- Cinobufotalin Ameliorates the Development of Pulmonary Fibrosis by Suppressing the TGF-β/Smad Pathway via Regulating PI15.Journal of cellular and molecular medicine · 2025Article
- Cardiac Glycosides: From Natural Defense Molecules to Emerging Therapeutic Agents.Biomolecules · 2025Review
- Integrated bioinformatics and functional studies identify CDK9 as a potential prognostic biomarker and therapeutic target in AML.Discover oncology · 2025Article
- α-Mangostin Exhibits Antitumor Activity Against NCI-H1975 Cells via the EGFR/STAT3 Pathway: An Experimental and Molecular Simulation Study.Molecules (Basel, Switzerland) · 2025Article
- CREPT promotes LUAD progression by enhancing the CDK9 and RNAPII assembly to promote ERK-driven gene transcription.Theranostics · 2025Article
- Bufadienolides from Chansu Injection Synergistically Enhances the Antitumor Effect of Erlotinib by Inhibiting the KRAS Pathway in Pancreatic Cancer.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Ameliorative effects of Turbinaria ornata extract on hepatocellular carcinoma induced by diethylnitrosamine in-vivo.Journal of molecular histology · 2024Article
- The diagnostic value investigation of programmed cell death genes in heart failure.BMC cardiovascular disorders · 2024Article
- Unraveling the Molecular Mechanisms of SIRT7 in Angiogenesis: Insights from Substrate Clues.International journal of molecular sciences · 2024Review
- Combinational Antitumor Strategies Based on the Active Ingredients of Toad Skin and Toad Venom.Drug design, development and therapy · 2024Review
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCyclin-dependent kinase 9 (CDK9) is a promising prognostic marker and therapeutic target in cancers. Bufalin is an effective anti-tumour agent; however, the clinical application of bufalin is limited due to its high toxicity. Acetyl-bufalin, the bufalin prodrug, was designed and synthesised with higher efficiency and lower toxicity.
methodsThree non-small-cell lung cancer (NSCLC) cell lines, a xenograft model and a patient-derived xenograft (PDX) model were used to examine the effects of acetyl-bufalin. CDK9/STAT3 involvement was investigated by knockdown with siRNA, proteome microarray assay, western blot analysis and co-immunoprecipitation experiments. Acute toxicity test and pharmacokinetics (PK) study were conducted to assess the safety and PK. The human NSCLC tissues were analysed to verify high CDK9 expression.
resultsWe showed that CDK9 induced NSCLC cell proliferation and that this effect was associated with STAT3 activation, specifically an increase in STAT3 phosphorylation and transcription factor activity. Acetyl-bufalin is an effective and safety inhibitor of the CDK9/STAT3 pathway, leading to the impediment of various oncogenic processes in NSCLC. Molecular docking and high-throughput proteomics platform analysis uncovered acetyl-bufalin directly binds to CDK9. Consequently, acetyl-bufalin impaired the complex formation of CDK9 and STAT3, decreased the expressions of P-STAT3, and transcribed target genes such as cyclin B1, CDC2, MCL-1, Survivin, VEGF, BCL2, and it upregulated the expression levels of BAX and caspase-3 activity. Acetyl-bufalin inhibited tumour growth in NSCLC xenograft and PDX models.
conclusionsAcetyl-bufalin is a novel blocker of the CDK9/STAT3 pathway thus may have potential in therapy of NSCLC and other cancers.
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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.