ArticleActa pharmacologica Sinica2019
Eukaryotic elongation factor-2 kinase regulates the cross-talk between autophagy and pyroptosis in doxorubicin-treated human melanoma cells in vitro.
Article in Acta pharmacologica Sinica, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 127 citations in OpenAlex.
- Synergistic effects of cold atmospheric plasma and doxorubicin on melanoma: A systematic review and meta-analysis.Scientific reports · 2025Pooled it
- Metabolism, autophagy, and cell death: The triangular axis in tumor survival and therapeutic resistance.Redox biology · 2026Review
- The pyroptosis and inflammatory response-related long noncoding RNA signature as a novel prognostic biomarker of head and neck squamous cell carcinoma.Discover oncology · 2026Article
- Oxeiptosis - potential in cancer treatment?Expert reviews in molecular medicine · 2026Review
- Autophagy regulation of pyroptosis and ferroptosis: a new strategy for colorectal cancer treatment.Apoptosis : an international journal on programmed cell death · 2026Review
- FGD3 mediates lytic cell death, enhancing efficacy and immunogenicity of chemotherapy agents in breast cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- Arsenic trioxide-based nanoparticles for enhanced chemotherapy by activating pyroptosis.Acta pharmaceutica Sinica. B · 2025Article
- Targeting metalloptosis in tumor therapy: from molecular mechanisms to application of metal nanoparticles.Molecular cancer · 2025Review
- Inhibition of PINK1 senses ROS signaling to facilitate neuroblastoma cell pyroptosis.Autophagy · 2025Article
- Pyroptosis and chemical classification of pyroptotic agents.Molecular diversity · 2025Review
- Targeting pyroptosis for cancer immunotherapy: mechanistic insights and clinical perspectives.Molecular cancer · 2025Review
- Manipulation of cancer cell pyroptosis for therapeutic approaches: challenges and opportunities.Biomarker research · 2025Review
- Nanomaterials evoke pyroptosis boosting cancer immunotherapy.Acta pharmaceutica Sinica. B · 2025Review
- Ferroptosis and pyroptosis are connected through autophagy: a new perspective of overcoming drug resistance.Molecular cancer · 2025Review
- Advances in non-apoptotic regulated cell death: implications for malignant tumor treatment.Frontiers in oncology · 2025Review
- Prognostic implications of autophagy and pyroptosis related genes in oral squamous cell carcinoma: research on bioinformatics and experiments.Frontiers in oncology · 2025Article
- Licochalcone A suppresses pancreatic ductal adenocarcinoma progression by targeting eEF2K-mediated pyroptosis.Frontiers in pharmacology · 2025Article
- The gasdermin family: emerging therapeutic targets in diseases.Signal transduction and targeted therapy · 2024Review
- Pyroptosis in cancer treatment and prevention: the role of natural products and their bioactive compounds.Medical oncology (Northwood, London, England) · 2024Review
- Chloroquine and Chemotherapeutic Compounds in Experimental Cancer Treatment.International journal of molecular sciences · 2024Review
16 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Eukaryotic elongation factor-2 kinase (eEF-2K), a negative regulator of protein synthesis, has been shown to play an important role in modulating autophagy and apoptosis in tumor cells under various stresses. In this study, we investigated the regulatory role of eEF-2K in pyroptosis (a new form of programmed necrosis) in doxorubicin-treated human melanoma cells. We found that doxorubicin (0.5-5 μmol/L) induced pyroptosis in melanoma cell lines SK-MEL-5, SK-MEL-28, and A-375 with high expression of DFNA5, but not in human breast cancer cell line MCF-7 with little expression of DFNA5. On the other hand, doxorubicin treatment activated autophagy in the melanoma cells; inhibition of autophagy by transfecting the cells with siRNA targeting Beclin1 or by pretreatment with chloroquine (20 μmol/L) significantly augmented pyroptosis, thus sensitizing the melanoma cells to doxorubicin. We further demonstrated that doxorubicin treatment activated eEF-2K in the melanoma cells, and silencing of eEF-2K blunted autophagic responses, but promoted doxorubicin-induced pyroptotic cell death. Taken together, the above results demonstrate that eEF-2K dictates the cross-talk between pyroptosis and autophagy in doxorubicin-treated human melanoma cells; suppression of eEF-2K results in inhibiting autophagy and augmenting pyroptosis, thus modulating the sensitivity of melanoma cells to doxorubicin, suggesting that targeting eEF-2K may reinforce the antitumor efficacy of doxorubicin, offering a new insight into tumor chemotherapy.
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