ArticleCell death & disease2019
The fungal metabolite chaetocin is a sensitizer for pro-apoptotic therapies in glioblastoma.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 36 citations in OpenAlex.
- Helping Apo2L/TRAIL in the Battle: Synergistic Therapeutic Approaches for Cancer Therapies.International journal of molecular sciences · 2026Review
- Genetically engineered human cell-based microrobots for selective cancer cell death.Science advances · 2026Article
- SUV family histone methyltransferases correlate with nuclear lamina remodeling and clinical outcome in cancer: integrative pan-cancer TCGA analysis and experimental evidence.Scientific reports · 2026Article
- Chaetocin enhances tumor necrosis factor‑related apoptosis‑inducing ligand‑mediated apoptosis by enhancing DR5 stabilization and reactive oxygen species generation in human glioblastoma cells.International journal of oncology · 2025Article
- Targeted Regulation of HSP70 by the ARP2/3 Complex in Mammary Epithelial Cells and Its Impact on Host Cell Apoptosis.Biomolecules · 2025Article
- Chaetocin, a Natural Inhibitor of Transketolase, Suppresses the Non-Oxidative Pentose Phosphate Pathway and Inhibits the Growth of Drug-Resistant Non-Small Cell Lung Cancer.Antioxidants (Basel, Switzerland) · 2025Article
- SUV39H1 maintains cancer stem cell chromatin state and properties in glioblastoma.JCI insight · 2025Article
- Nuclear translocation of ISG15 regulated by PPP2R2B inhibits cisplatin resistance of bladder cancer.Cellular and molecular life sciences : CMLS · 2024Article
- Chemical Genetics inACS chemical biology · 2024Article
- Chaetocin-mediated SUV39H1 inhibition targets stemness and oncogenic networks of diffuse midline gliomas and synergizes with ONC201.Neuro-oncology · 2024Article
- Natural compound chaetocin induced DNA damage and apoptosis through reactive oxygen species-dependent pathways in A549 lung cancer cells and in vitro evaluations.IET nanobiotechnology · 2023Article
- Article
- Chaetocin exhibits anticancer effects in esophageal squamous cell carcinoma via activation of Hippo pathway.Aging · 2023Article
- Perturbation Analysis of a PrognosticCells · 2023Article
- ROS regulation in gliomas: implications for treatment strategies.Frontiers in immunology · 2023Review
- A novel BH3 mimetic Bcl-2 inhibitor promotes autophagic cell death and reduces in vivo Glioblastoma tumor growth.Cell death discovery · 2022Article
- Activated TRPA1 plays a therapeutic role in TMZ resistance in glioblastoma by altering mitochondrial dynamics.BMC molecular and cell biology · 2022Article
- Potential targets and treatments affect oxidative stress in gliomas: An overview of molecular mechanisms.Frontiers in pharmacology · 2022Review
- Article
- A System Bioinformatics Approach Predicts the Molecular Mechanism Underlying the Course of Action of Radix Salviae Reverses GBM Effects.Evidence-based complementary and alternative medicine : eCAM · 2021Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
Abstract
Glioblastoma Multiforme (GBM) is the most common and aggressive primary brain tumor. Despite recent developments in surgery, chemo- and radio-therapy, a currently poor prognosis of GBM patients highlights an urgent need for novel treatment strategies. TRAIL (TNF Related Apoptosis Inducing Ligand) is a potent anti-cancer agent that can induce apoptosis selectively in cancer cells. GBM cells frequently develop resistance to TRAIL which renders clinical application of TRAIL therapeutics inefficient. In this study, we undertook a chemical screening approach using a library of epigenetic modifier drugs to identify compounds that could augment TRAIL response. We identified the fungal metabolite chaetocin, an inhibitor of histone methyl transferase SUV39H1, as a novel TRAIL sensitizer. Combining low subtoxic doses of chaetocin and TRAIL resulted in very potent and rapid apoptosis of GBM cells. Chaetocin also effectively sensitized GBM cells to further pro-apoptotic agents, such as FasL and BH3 mimetics. Chaetocin mediated apoptosis sensitization was achieved through ROS generation and consequent DNA damage induction that involved P53 activity. Chaetocin induced transcriptomic changes showed induction of antioxidant defense mechanisms and DNA damage response pathways. Heme Oxygenase 1 (HMOX1) was among the top upregulated genes, whose induction was ROS-dependent and HMOX1 depletion enhanced chaetocin mediated TRAIL sensitization. Finally, chaetocin and TRAIL combination treatment revealed efficacy in vivo. Taken together, our results provide a novel role for chaetocin as an apoptosis priming agent and its combination with pro-apoptotic therapies might offer new therapeutic approaches for GBMs.
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