ArticleInternational journal of oncology2018
Cytocidal effects of arenobufagin and hellebrigenin, two active bufadienolide compounds, against human glioblastoma cell line U-87.
Article in International journal of oncology, 2018. 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, 36 citations in OpenAlex.
- Advances in targeting p38 MAPK for cancer therapy: insights from molecular pharmacology and medicinal chemistry.Molecular diversity · 2026Review
- Nutraceutical Characterization, 3D Airway Tissue Metabolic Viability, and Cytotoxic Activity ofMedicina (Kaunas, Lithuania) · 2026Article
- Comparative In Vitro Response of HaCaT and A375 Melanoma Cells to Zinc Oxide Nanoparticles Synthesized Using Puerarin.Journal of xenobiotics · 2026Article
- Novel Phenethylamine-Based Aroyl Thiourea Derivatives: Design, Synthesis, and Multibiological Evaluation.ACS omega · 2026Article
- Exploring Thymol's Cytocompatibility and Potential Selective Cytotoxicity in Human Primary Gingival Fibroblasts and Pharyngeal Carcinoma Cells: An In Vitro and In Ovo Investigation.Dentistry journal · 2026Article
- Silibinin Triggers Mitochondrial Apoptosis and Declines Clonogenic Potential in Detroit 562 Human Pharyngeal Carcinoma Cells.Medicina (Kaunas, Lithuania) · 2025Article
- Cellular and molecular mechanisms of arenobufagin in cancer therapy: a systematic review.Discover oncology · 2025Review
- The Efficacy of Hellebrigenin Against Nasopharyngeal Carcinoma Cells: The Molecular and Bioinformatic Analysis.Journal of cellular and molecular medicine · 2025Article
- Preclinical pharmaco-toxicological screening of biomimetic melanin-like nanoparticles as a potential therapeutic strategy for cutaneous melanoma.Frontiers in pharmacology · 2025Article
- Review
- Bufadienolides from Chansu Injection Synergistically Enhances the Antitumor Effect of Erlotinib by Inhibiting the KRAS Pathway in Pancreatic Cancer.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Pharmacological insights and role of bufalin (bufadienolides) in inflammation modulation: a narrative review.Inflammopharmacology · 2024Review
- Chemical Composition, Pharmacological Effects and Clinical Applications of Cinobufacini.Chinese journal of integrative medicine · 2024Review
- Metabolomics of cerebrospinal fluid reveals candidate diagnostic biomarkers to distinguish between spinal muscular atrophy type II and type III.CNS neuroscience & therapeutics · 2024Article
- Hellebrigenin induces oral cancer cell apoptosis by modulating MAPK signalling and XIAP expression.Journal of cellular and molecular medicine · 2024Article
- Article
- Enhanced Cytotoxic Effects of Arenite in Combination with Active Bufadienolide Compounds against Human Glioblastoma Cell Line U-87.Molecules (Basel, Switzerland) · 2022Article
- The functional role of p38 MAPK pathway in malignant brain tumors.Frontiers in pharmacology · 2022Review
- Novel Strategies for Solubility and Bioavailability Enhancement of Bufadienolides.Molecules (Basel, Switzerland) · 2021Review
- Bersaldegenin-1,3,5-orthoacetate induces caspase-independent cell death, DNA damage and cell cycle arrest in human cervical cancer HeLa cells.Pharmaceutical biology · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glioblastoma is the most common and lethal intracranial tumor type, characterized by high angiogenic and infiltrative capacities. To provide a novel insight into therapeutic strategies against glioblastoma, the cytotoxicity of arenobufagin and hellebrigenin was investigated in the human glioblastoma cell line, U-87. Similar dose-dependent cytotoxicity was observed in the cells, whereas no detectable toxicity was confirmed in mouse primary astrocytes. Treatment with each drug downregulated the expression levels of Cdc25C, Cyclin B1 and survivin, which occurred in parallel with G2/M phase arrest. Necrotic-like cell death was only observed in the cells treated with a relatively high concentration (>100 ng/ml). These results indicate that the two drugs exhibited distinct cytotoxicity against cancerous glial cells with high potency and selectivity, suggesting that growth inhibition associated with G2/M phase arrest and/or necrosis were attributed to their toxicities. Activation of the p38 mitogen activated protein kinase (MAPK) signaling pathway was also observed in treated cells. Notably, a specific inhibitor of p38 MAPK, SB203580, itself caused a significant decrease in cell viability, and further enhanced the cytotoxicity of the two drugs, suggesting an important pro-survival role for p38 MAPK. Given that p38 MAPK serves an essential role in promoting glioblastoma cell survival, developing a novel combination regimen of arenobufagin/hellebrigenin plus a p38 MAPK inhibitor may improve the efficacy of the two drugs, and may provide more therapeutic benefits to patients with glioblastoma. The qualitative assessment demonstrated the existence of arenobufagin in the cerebrospinal fluid of arenobufagin-treated rats, supporting its clinical application.
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Registered trials
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