ArticleInternational journal of molecular sciences2022
Bufalin Inhibits Tumorigenesis, Stemness, and Epithelial-Mesenchymal Transition in Colorectal Cancer through a C-Kit/Slug Signaling Axis.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Efficacy and safety of cinobufacini capsules combined with oxaliplatin-based chemotherapy for advanced colorectal cancer: a human systematic review and meta-analysis.Frontiers in pharmacology · 2026Pooled it
- Cardiac Glycoside 3β-Bufalin Suppresses Cancer Cell Proliferation by Coupling with NaInternational journal of molecular sciences · 2026Article
- Role of epithelial-mesenchymal transition (EMT) in malignancies: current status and future prospects.Signal transduction and targeted therapy · 2026Review
- Testican-1 activates Wnt/β-Catenin signaling to drive colorectal cancer progression.Oncogenesis · 2026Article
- A narrative review of cinobufacini for endometrial cancer: mechanisms and therapeutic implications.Translational cancer research · 2026Review
- Patient-Derived Organoids as a Platform to Decipher and Overcome Radioresistance: From the Tumor Microenvironment to Radiosensitizer Discovery.Current oncology (Toronto, Ont.) · 2025Review
- Epithelial-mesenchymal transition in colorectal cancer metastasis and progression: molecular mechanisms and therapeutic strategies.Cell death discovery · 2025Review
- Cardiac Glycosides: From Natural Defense Molecules to Emerging Therapeutic Agents.Biomolecules · 2025Review
- Progress of traditional Chinese medicine in the prevention and treatment of colorectal cancer.World journal of gastrointestinal oncology · 2025Review
- Bufadienolides from Chansu Injection Synergistically Enhances the Antitumor Effect of Erlotinib by Inhibiting the KRAS Pathway in Pancreatic Cancer.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Influence of Different Ratios of DSPE-PEG2k on Ester Prodrug Self-Assembly Nanoparticles for Cell Migration and Proliferation Suppression.International journal of nanomedicine · 2024Article
- [Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2023Article
- Bufalin reverses cancer-associated fibroblast-mediated colorectal cancer metastasis by inhibiting the STAT3 signaling pathway.Apoptosis : an international journal on programmed cell death · 2023Article
- Bufalin-Mediated Regulation of Cell Signaling Pathways in Different Cancers: Spotlight on JAK/STAT, Wnt/β-Catenin, mTOR, TRAIL/TRAIL-R, and Non-Coding RNAs.Molecules (Basel, Switzerland) · 2023Review
- c-Kit Receptors as a Therapeutic Target in Cancer: Current Insights.OncoTargets and therapy · 2023Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Colorectal cancer (CRC) is a major source of morbidity and mortality, characterized by intratumoral heterogeneity and the presence of cancer stem cells (CSCs). Bufalin has potent activity against many tumors, but studies of its effect on CRC stemness are limited. We explored bufalin's function and mechanism using CRC patient-derived organoids (PDOs) and cell lines. In CRC cells, bufalin prevented nuclear translocation of β-catenin and down-regulated CSC markers (CD44, CD133, LGR5), pluripotency factors, and epithelial-mesenchymal transition (EMT) markers (N-Cadherin, Slug, ZEB1). Functionally, bufalin inhibited CRC spheroid formation, aldehyde dehydrogenase activity, migration, and invasion. Network analysis identified a C-Kit/Slug signaling axis accounting for bufalin's anti-stemness activity. Bufalin treatment significantly downregulated C-Kit, as predicted. Furthermore, overexpression of C-Kit induced Slug expression, spheroid formation, and bufalin resistance. Similarly, overexpression of Slug resulted in increased expression of C-Kit and identical functional effects, demonstrating a pro-stemness feedback loop. For further study, we established PDOs from diagnostic colonoscopy. Bufalin differentially inhibited PDO growth and proliferation, induced apoptosis, restored E-cadherin, and downregulated CSC markers CD133 and C-Myc, dependent on C-Kit/Slug. These findings suggest that the C-Kit/Slug axis plays a pivotal role in regulating CRC stemness, and reveal that targeting this axis can inhibit CRC growth and progression.
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Registered trials
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.