ArticleCell proliferation2020
Gamabufotalin induces a negative feedback loop connecting ATP1A3 expression and the AQP4 pathway to promote temozolomide sensitivity in glioblastoma cells by targeting the amino acid Thr794.
Article in Cell proliferation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Gamabufotalin suppresses pancreatic cancer through redox-homeostasis disruption by G6PD downregulation.Journal of translational medicine · 2026Article
- Cardiac Glycosides: From Natural Defense Molecules to Emerging Therapeutic Agents.Biomolecules · 2025Review
- CS-6-induced p62 accumulation exacerbates DNA damage in colorectal cancer.Frontiers in pharmacology · 2025Article
- Review
- Update on the intriguing roles of AQP4 expression and redistribution in the progression and treatment of glioma.Annals of medicine · 2024Review
- Deciphering MOSPD1's impact on breast cancer progression and therapeutic response.Biology direct · 2024Article
- Multiomics2Targets identifies targets from cancer cohorts profiled with transcriptomics, proteomics, and phosphoproteomics.Cell reports methods · 2024Article
- Preclinical and clinical advances to overcome hypoxia in glioblastoma multiforme.Cell death & disease · 2024Review
- Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives.Journal of hematology & oncology · 2024Review
- Contribution of m5C RNA Modification-Related Genes to Prognosis and Immunotherapy Prediction in Patients with Ovarian Cancer.Mediators of inflammation · 2023Article
- The role of aquaporin 4 in brain tumors: implications for pathophysiology, diagnosis and therapy.Molecular biology reports · 2022Review
- Enhanced Cytotoxic Effects of Arenite in Combination with Active Bufadienolide Compounds against Human Glioblastoma Cell Line U-87.Molecules (Basel, Switzerland) · 2022Article
- Potassium channel-related genes are a novel prognostic signature for the tumor microenvironment of renal clear cell carcinoma.Frontiers in oncology · 2022Article
- Identification of the prognostic and immunological roles of aquaporin 4: A potential target for survival and immunotherapy in glioma patients.Frontiers in cellular neuroscience · 2022Article
- A Bioinformatics Analysis of the Potential Roles of Aquaporin 4 in Human Brain Tumors: An Immune-Related Process.Frontiers in pharmacology · 2021Article
- Gamabufotalin induces a negative feedback loop connecting ATP1A3 expression and the AQP4 pathway to promote temozolomide sensitivity in glioblastoma cells by targeting the amino acid Thr794.Cell proliferation · 2020Article
- Gamabufotalin Suppresses Colorectal Cancer Growth via Oxidative Stress-Induced Apoptosis and DNA Synthesis Inhibition.Iranian journal of pharmaceutical research : IJPRArticle
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
objectivesTemozolomide (TMZ) is one of the most commonly used clinical drugs for glioblastoma (GBM) treatment, but its drug sensitivity needs to be improved. Gamabufotalin (CS-6), the primary component of the traditional Chinese medicine "ChanSu," was shown to have strong anti-cancer activity. However, more efforts should be directed towards reducing its toxicity or effective treatment doses.
methodsTarget fishing experiment, Western blotting, PCR, confocal immunofluorescence and molecular cloning techniques were performed to search for possible downstream signalling pathways. In addition, GBM xenografts were used to further determine the potential molecular mechanisms of the synergistic effects of CS-6 and TMZ in vivo.
resultsMechanistic research revealed a negative feedback loop between ATP1A3 and AQP4 through which CS-6 inhibited GBM growth and mediated the synergistic treatment effect of CS-6 and TMZ. In addition, by mutating potential amino acid residues of ATP1A3, which were predicted by modelling and docking to interact with CS-6, we demonstrated that abrogating hydrogen bonding of the amino acid Thr794 interferes with the activation of ATP1A3 by CS-6 and that the Thr794Ala mutation directly affects the synergistic treatment efficacy of CS-6 and TMZ.
conclusionsAs the main potential target of CS-6, ATP1A3 activation critically depends on the hydrogen bonding of Thr794 with CS-6. The combination of CS-6 and TMZ could significantly reduce the therapeutic doses and promote the anti-cancer efficacy of CS-6/TMZ monotherapy.
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