ArticleOncotarget2016
Obatoclax kills anaplastic thyroid cancer cells by inducing lysosome neutralization and necrosis.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Cyclin C promotes pancreatic developmentand suppresses cancer initiation by maintenance of the autophagy-lysosome pathway.iScience · 2026Article
- Loss of ADAM15 prevents necroptosis induction by partial RIPK1 degradation due to enhanced TNF-R1 surface expression and basal caspase-8 activation.Cell communication and signaling : CCS · 2025Article
- Targeting Glycolysis with 2-Deoxy-D-Glucose and Lysosomal Integrity with L-Leucyl-L-Leucine Methyl Ester as Antimelanoma Strategy.Pharmaceutics · 2025Article
- A novel approach to regulate glucose uptake in an anaplastic thyroid cancer cell line.Endocrine connections · 2025Article
- Article
- Prognostic significance and immunological role of HPRT1 in human cancers.Biomolecules & biomedicine · 2024Article
- Nanomedicine for cancer targeted therapy with autophagy regulation.Frontiers in immunology · 2023Review
- Modulating lysosomal pH: a molecular and nanoscale materials design perspective.Journal of life sciences (Westlake Village, Calif.) · 2020Article
- Synergistic repression of thyroid hyperplasia by cyclin C and Pten.Journal of cell science · 2019Article
- [Bortezomib and obatoclax for dual blockade of protein degradation pathways show synergistic anti-tumor effect in human acute T lymphoblastic leukemia cells].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2019Article
- Obatoclax, a BH3 Mimetic, Enhances Cisplatin-Induced Apoptosis and Decreases the Clonogenicity of Muscle Invasive Bladder Cancer Cells via Mechanisms That Involve the Inhibition of Pro-Survival Molecules as Well as Cell Cycle Regulators.International journal of molecular sciences · 2019Article
- Obatoclax and Paclitaxel Synergistically Induce Apoptosis and Overcome Paclitaxel Resistance in Urothelial Cancer Cells.Cancers · 2018Article
- Therapeutic advances in anaplastic thyroid cancer: a current perspective.Molecular cancer · 2018Review
- Typical and Atypical Inducers of Lysosomal Cell Death: A Promising Anticancer Strategy.International journal of molecular sciences · 2018Review
- Article
- Obatoclax Inhibits Alphavirus Membrane Fusion by Neutralizing the Acidic Environment of Endocytic Compartments.Antimicrobial agents and chemotherapy · 2017Article
- Obatoclax and LY3009120 Efficiently Overcome Vemurafenib Resistance in Differentiated Thyroid Cancer.Theranostics · 2017Article
- Hypericin-mediated sonodynamic therapy induces autophagy and decreases lipids in THP-1 macrophage by promoting ROS-dependent nuclear translocation of TFEB.Cell death & disease · 2016Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Poorly differentiated and anaplastic thyroid carcinomas are very aggressive, almost invariably lethal neoplasms for which no effective treatment exists. These tumors are intrinsically resistant to cell death, even when their driver oncogenic signaling pathways are inhibited.We have undertaken a detailed analysis, in mouse and human thyroid cancer cells, of the mechanism through which Obatoclax, a pan-inhibitor of the anti-apoptotic proteins of the BCL2 family, effectively reduces tumor growth in vitro and in vivo.We demonstrate that Obatoclax does not induce apoptosis, but rather necrosis of thyroid cancer cells, and that non-transformed thyroid cells are significantly less affected by this compound. Surprisingly, we show that Obatoclax rapidly localizes to the lysosomes and induces loss of acidification, block of lysosomal fusion with autophagic vacuoles, and subsequent lysosomal permeabilization. Notably, prior lysosome neutralization using different V-ATPase inhibitors partially protects cancer cells from the toxic effects of Obatoclax. Although inhibition of autophagy does not affect Obatoclax-induced cell death, selective down-regulation of ATG7, but not of ATG5, partially impairs Obatoclax effects, suggesting the existence of autophagy-independent functions for ATG7. Strikingly, Obatoclax killing activity depends only on its accumulation in the lysosomes, and not on its interaction with BCL2 family members.Finally, we show that also other lysosome-targeting compounds, Mefloquine and LLOMe, readily induce necrosis in thyroid cancer cells, and that Mefloquine significantly impairs tumor growth in vivo, highlighting a clear vulnerability of these aggressive, apoptosis-resistant tumors that can be therapeutically exploited.
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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.