ArticleOncotarget2017
The tubulin inhibitor MG-2477 induces autophagy-regulated cell death, ROS accumulation and activation of FOXO3 in neuroblastoma.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- Multiple Regulatory Mechanisms of Post-Translational Modifications and Therapeutic Potential of Mitotic Catastrophe.International journal of molecular sciences · 2026Review
- Inflammatory transcriptomic signatures in a human cellular NMOSD model reveal upregulation of NF-κB and IL6 pathways.Scientific reports · 2025Article
- An overview of neuroblastoma cell lineage phenotypes andExperimental biology and medicine (Maywood, N.J.) · 2020Review
- Article
- Article
- Autophagy, apoptosis, and mitochondria: molecular integration and physiological relevance in skeletal muscle.American journal of physiology. Cell physiology · 2019Article
- In Vitro Anti-proliferative Activity and Mechanism of Action ofInternational journal of molecular sciences · 2019Article
- miR‑122 promotes proliferation and invasion of clear cell renal cell carcinoma by suppressing Forkhead box O3.International journal of oncology · 2019Article
- Modulation of Respiration and Mitochondrial Dynamics by SMAC-Mimetics for Combination Therapy in Chemoresistant Cancer.Theranostics · 2019Article
- FOXO3-mediated chemo-protection in high-stage neuroblastoma depends on wild-type TP53 and SESN3.Oncogene · 2017Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
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Abstract
Neuroblastoma is the most frequent extra-cranial solid tumor in children with still high mortality in stage M. Here we studied the tubulin-inhibitor MG-2477 as a possible therapeutic agent for neuroblastoma therapy and uncovered that MG-2477 induces death in neuroblastoma cells independent of PKB-activation status and stage. MG-2477 triggers within 30 minutes extensive autophagosome-formation that finally leads to cell death associated with mitotic catastrophe. Autophagy is critical for MG-2477-induced death and is regulated by the BH3-only protein PMAIP1/NOXA which sequesters the anti-apoptotic BCL2-protein BCLXL and thereby displaces and activates the autophagy-regulator BECN1/beclin1. Knockdown of NOXA or overexpression of its pro-survival binding partners MCL1 and BCLXL counteracts MG-2477-induced cell death. MG-2477 also rapidly induces the repression of the anti-apoptotic protein Survivin, which promotes autophagy and cell death. We further observed the accumulation of reactive oxygen species (ROS) that triggers autophagy induction suggesting a change of the PI3 kinase-III/BECN1 complex and activates the transcription factor FOXO3, which contributes to final cell death induction. The combined data suggest that MG-2477 induces a sequential process of ROS-accumulation, autophagy and FOXO3-activation that leads to cell death in neuroblastoma cells.
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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.