ArticleOncotarget2017
BH3 mimetic Obatoclax (GX15-070) mediates mitochondrial stress predominantly via MCL-1 inhibition and induces autophagy-dependent necroptosis in human oral cancer cells.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
- Prodigiosin in glioblastoma: mechanistic pharmacology and rationale for its development as a radiosensitiser.Frontiers in pharmacology · 2026Review
- 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
- Inhibition of anti-apoptotic Bcl-2 family members promotes synergistic cell death with ER stress inducers by disrupting autophagy in glioblastoma.Cell death discovery · 2025Article
- [Cisplatin promotes TNF-α autocrine to trigger RIP1/RIP3/MLKL-dependent necroptosis of human head and neck squamous cell carcinoma cells].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Article
- Review
- Prognostic Value of Necroptosis-Related Genes Signature in Oral Squamous Cell Carcinoma.Cancers · 2023Article
- Involvement of necroptosis in the selective toxicity of the natural compound (±) gossypol on squamous skin cancer cells in vitro.Archives of toxicology · 2023Article
- Identification of bicyclic compounds that act as dual inhibitors of Bcl-2 and Mcl-1.Molecular diversity · 2023Article
- Article
- Nanomedicine for cancer targeted therapy with autophagy regulation.Frontiers in immunology · 2023Review
- Autophagy and Apoptosis: Current Challenges of Treatment and Drug Resistance in Multiple Myeloma.International journal of molecular sciences · 2022Review
- Necroptosis: A Pathogenic Negotiator in Human Diseases.International journal of molecular sciences · 2022Review
- Molecular Mechanisms of Autophagy in Cancer Development, Progression, and Therapy.Biomedicines · 2022Review
- Cell Death and the p53 Enigma During Mammalian Embryonic Development.Stem cells (Dayton, Ohio) · 2022Review
- Myeloid cell leukemia-1: a formidable barrier to anticancer therapeutics and the quest of targeting it.Exploration of targeted anti-tumor therapy · 2022Review
- BH3-mimetics: recent developments in cancer therapy.Journal of experimental & clinical cancer research : CR · 2021Review
- Review
- Elevated USP9X drives early-to-late-stage oral tumorigenesis via stabilisation of anti-apoptotic MCL-1 protein and impacts outcome in oral cancers.British journal of cancer · 2021Article
- The interplay of autophagy and non-apoptotic cell death pathways.International review of cell and molecular biology · 2020Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have previously reported overexpression of antiapoptotic MCL-1 protein in human oral cancers and its association with therapy resistance and poor prognosis, implying it to be a potential therapeutic target. Hence, we investigated the efficacy and mechanism of action of Obatoclax, a BH3 mimetic pan BCL-2 inhibitor in human oral cancer cell lines. All cell lines exhibited high sensitivity to Obatoclax with complete clonogenic inhibition at 200-400 nM concentration which correlated with their MCL-1 expression. Mechanistic insights revealed that Obatoclax induced a caspase-independent cell death primarily by induction of a defective autophagy. Suppression of autophagy by ATG5 downregulation significantly blocked Obatoclax-induced cell death. Further, Obatoclax induced interaction of p62 with key components of the necrosome RIP1K and RIP3K. Necrostatin-1 mediated inhibition of RIP1K significantly protected the cells from Obatoclax induced cell death. Moreover, Obatoclax caused extensive mitochondrial stress leading to their dysfunction. Interestingly, MCL-1 downregulation alone caused mitochondrial stress, highlighting its importance for mitochondrial homeostasis. We also demonstrated
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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.