ArticleInternational journal of biological sciences2022
Toosendanin, a novel potent vacuolar-type H
Article in International journal of biological sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 38 citations in OpenAlex.
- Recent progress in small molecules targeting the acidic tumor microenvironment.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Compartmental pH regulation in cancer and antitumor immunity: therapeutic opportunities and challenges.Apoptosis : an international journal on programmed cell death · 2026Review
- A hub for an herb: is STAT3 blockade at the epicenter of toosendanin-induced NCOA4-dependent ferritinophagy and ferroptosis in cancer cells?Journal of gastrointestinal oncology · 2026Article
- Toosendanin Alleviates Cerebral Ischemia/Reperfusion Injury via Inhibiting Neural Ferroptosis Through Lipid Metabolic Reprogramming in MCAO Mice.CNS neuroscience & therapeutics · 2026Article
- DeepDrugDiscovery identifies blood-brain barrier permeable autophagy enhancers for Alzheimer's disease.Nature biomedical engineering · 2026Article
- Toosendanin enhances endothelial repair and prevents inflammation via E2F1 mediated LINC01089.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Remimazolam Attenuates Neurological Injury After TBI: A Potential Role of α7nAChR-Associated Mitophagy Enhancement and Pyroptosis Suppression in BV2 Cells.Drug design, development and therapy · 2026Article
- Targeting autophagy in dysfunctional tumor vasculature.iScience · 2025Review
- Acidic Tumor Microenvironments and Emerging Therapeutic Strategies for Cancer Therapy.Yonsei medical journal · 2025Review
- Practical implementation and impact of the 4R principles in ethnopharmacology: Pursuing a more humane approach to research.Frontiers in pharmacology · 2025Review
- Integrated thermal proteome and thermal proximity co-aggregation profiling identifies ATP6V1C1 as a novel anti-cancer drug target.International journal of biological sciences · 2025Article
- Discovery of vitexin as a novel VDR agonist that mitigates the transition from chronic intestinal inflammation to colorectal cancer.Molecular cancer · 2024Article
- Increased V-ATPase activity can lead to chemo-resistance in oral squamous cell carcinoma via autophagy induction: new insights.Medical oncology (Northwood, London, England) · 2024Review
- SEC23A confers ER stress resistance in gastric cancer by forming the ER stress-SEC23A-autophagy negative feedback loop.Journal of experimental & clinical cancer research : CR · 2023Article
- Calpains, the proteases of two faces controlling the epithelial homeostasis in mammary gland.Frontiers in cell and developmental biology · 2023Review
- Targeting HDAC6 to Overcome Autophagy-Promoted Anti-Cancer Drug Resistance.International journal of molecular sciences · 2022Review
- Insecticidal Triterpenes in Meliaceae: Plant Species, Molecules, and Activities: Part II (International journal of molecular sciences · 2022Review
- The therapeutic potential of natural products for treating pancreatic cancer.Frontiers in pharmacology · 2022Review
- TSN Disrupts Fanconi Anemia Pathway Activation Through JAK/STAT1-Mediated Transcriptional Repression of FA Core Subunits in Bladder Cancer.Dose-response : a publication of International Hormesis SocietyArticle
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Macroautophagy/autophagy is the process of self-digestion through the lysosomes; it disassembles unnecessary or dysfunctional long-lived proteins and damaged organelles for the recycling of biomacromolecules. Unfortunately, cancer cells can hijack this mechanism to survive under metabolic stress or develop drug resistance during chemotherapy. Increasing evidence indicates that the combination of autophagy inhibition and chemotherapy is a promising cancer treatment strategy. However, effective autophagy inhibitors with satisfied potency, bioavailability, and clearly-defined drug targets are still rare. Here, we report the identification of a potent autophagy inhibitor toosendanin which can effectively block autophagosome maturation, causing the accumulation of autophagy substrates in multiple cancer cells. Toosendanin did not inhibit the fusion process between autophagosome and lysosome but elevated lysosomal pH and impaired lysosomal enzymes activity. Using rat liver lysosome fraction and purified yeast V-ATPase, we found that toosendanin directly inhibited V-ATPase activity. By applying cellular thermal shift assay (CETSA), immunoprecipitation-coupled LC-MS/MS analysis, and biotin-toosendanin pull-down assay, we confirmed the direct binding between toosendanin and V-ATPase. Furthermore, toosendanin blocked chemotherapy-induced protective autophagy in cultured cancer cells and xenograft tumor tissues to significantly enhance anti-cancer activity. These results suggest that toosendanin has the potential to be developed into an anti-cancer drug by blocking chemotherapy-induced protective autophagy.
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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.