ArticleCell cycle (Georgetown, Tex.)2020
Metformin activates AMPK/SIRT1/NF-κB pathway and induces mitochondrial dysfunction to drive caspase3/GSDME-mediated cancer cell pyroptosis.
Article in Cell cycle (Georgetown, Tex.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 145 papers, 2 of them syntheses that pooled it.
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Who cites it
145 citing papers in PubMed, 2 syntheses or guidelines pooled it, 238 citations in OpenAlex.
- Interaction of HIF-1a with various cell death pathways in tumor immune microenvironment (TIME).Apoptosis : an international journal on programmed cell death · 2026Pooled it
- Diabetes Driven Oncogenesis and Anticancer Potential of Repurposed Antidiabetic Drug: A Systemic Review.Cell biochemistry and biophysics · 2024Pooled it
- Comparative Effects of Metformin, Boric Acid, and Lithium Chloride on Oxidative Stress-Mediated Cytotoxicity in HepG2 Hepatocarcinoma Cells.Biological trace element research · 2026Article
- Brain insulin resistance as a driver of proteinopathy in neurodegeneration: from cell-type-specific mechanisms to targeted therapeutics.Translational neurodegeneration · 2026Review
- Article
- The Role of Apoptosis and Ferroptosis in Primary Mitochondrial Diseases: Mechanisms and Pathogenesis.International journal of molecular sciences · 2026Review
- Carob pod aqueous extract potentiates cisplatin efficacy and reduces toxicity in experimental hepatocellular carcinoma via mitochondrial and inflammatory pathway modulation.Bioresources and bioprocessing · 2026Article
- The signaling and regulatory functions of dying cells and cell corpses.Communications biology · 2026Review
- RhFGF21 Mitigated D-gal-triggered Learning and Memory Dysfunction in Mice by Inhibiting Oxidative Stress, Inflammation and Senescence in Cortex and Hippocampus via Modulating FGFR1 and SIRT1.Molecular neurobiology · 2026Article
- BET inhibitors in cardiovascular diseases: from atherosclerosis to heart failure.Pharmacological reports : PR · 2026Review
- Dynamic magneto-mechanical force in lysosomes induces durable macrophage repolarization for antitumor immunity.Cell research · 2026Article
- The molecular mechanisms of pyroptosis and its implications in tumor immunotherapy.Molecular cancer · 2026Review
- Lactate Metabolism in the Intervertebral Disc: Mechanistic Insights and Pathological Implications.Biomolecules · 2026Review
- Activation of NF-κB signaling pathway in GSDME-low esophageal squamous cell carcinoma cells enhances radioresistance.Journal of translational medicine · 2026Article
- Upregulation of miR-223 by SIRT1 attenuates the inflammatory response in neonatal sepsis.BMC immunology · 2026Article
- Drug repurposing of sophoridine for sepsis-induced organ injury: from in-depth analysis of a single agent to a multi-target therapeutic paradigm.Frontiers in pharmacology · 2026Review
- Combination of metformin and parthenolide inhibits breast cancer in mice by apoptosis induction and angiogenesis inhibition.Frontiers in immunology · 2026Article
- Organelles and cancer cell pyroptosis: overview and perspectives.Cell death & disease · 2025Review
- Metformin mitigates cisplatin-induced premature ovarian insufficiency via Sirt1/Nrf2 activation.Medicine · 2025Article
- AMPK/SIRT1/PGC-1α Signaling Pathway: Molecular Mechanisms and Targeted Strategies From Energy Homeostasis Regulation to Disease Therapy.CNS neuroscience & therapeutics · 2025Review
85 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pyroptosis is a form of programmed cell death initiated by inflammasomes and is critical for immunity. SIRT1, a NAD+-dependent deacetylase, plays multiple roles in inflammatory response and immunity. Metformin can activate SIRT1 to participate in different biological processes and exert its anticancer effects. However, the mechanism by which metformin activates SIRT1 to drive cancer cell pyroptosis has not been reported. In this study, we treated cancer cells with metformin for diverse periods of time (0-24 h) and found that cell viability was decreased obviously. Interestingly, pyroptosis occurred when cancer cells were treated with metformin for the indicated time (4, 8 and 12 h), which was elucidated by the cell swelling and bubbles blowing in the membrane. Metformin also increased the release of lactate dehydrogenase (LDH, an indication of pyroptotic cell cytotoxicity) remarkably. The underlying mechanisms were that metformin enhanced AMPK/SIRT1 pathway and further increased NF-κB p65 expression to stimulate Bax activation and cytochrome c release, triggering caspase3 cleavage of GSDME, which is a characteristic pyroptotic marker. Depletion of SIRT1 inhibited metformin-induced these protein expression, revealing that metformin promotes AMPK/SIRT1/NF-κB signaling to drive cancer cell pyroptosis. Meantime, metformin induced mitochondrial dysfunction to trigger activation of caspase3 and generation of GSDME-N. Moreover, mitochondrial dysfunction activated AMPK/SIRT1 pathway to cause pyroptotic death upon metformin treatment. This research firstly reveals that metformin as a sensitizer amplifies AMPK/SIRT1/NF-κB signaling to induce caspase3/GSDME-mediated cancer cell pyroptosis. Induction of cellular pyroptosis by metformin is considered as a novel therapeutic option against various cancers.
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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.