ArticleCancer management and research2020
Metformin Induces Autophagy via the AMPK-mTOR Signaling Pathway in Human Hepatocellular Carcinoma Cells.
Article in Cancer management and research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Antiproliferative Mechanisms of Metformin in Breast Cancer: A Systematic Review of the Literature.International journal of molecular sciences · 2024Pooled it
- Autophagy in MASLD: A Metabolic and Precision Medicine Perspective.Liver international : official journal of the International Association for the Study of the Liver · 2026Review
- Metformin Redirects Autophagy from Bulk Turnover to Mitochondrial Clearance.bioRxiv : the preprint server for biology · 2026Article
- Repeat-associated non-AUG translation as a common mechanism for the polyGln ataxias.Cell reports · 2026Article
- Repurposing metformin for cardioprotection: mechanisms and therapeutic potential across cardiovascular pathologies.Frontiers in pharmacology · 2026Review
- Research Progress on the Molecular Mechanism of Metformin Regulating AMPK Signaling Pathway in Inhibiting Liver Cancer.OncoTargets and therapy · 2026Review
- Unravelling the Pathogenesis of Heart Failure with Preserved Ejection Fraction: The Pivotal Role of Autophagy and Endoplasmic Reticulum Stress.European cardiology · 2026Review
- Autophagy in tuberculosis: advances, translational gaps, and the promise of host-directed therapies.Frontiers in cellular and infection microbiology · 2026Review
- Antifungal effects of Metformin against Candida albicans by autophagy regulation.Journal of microbiology (Seoul, Korea) · 2025Article
- Roles of Oxidative Stress and Autophagy in Alcohol-Mediated Brain Damage.Antioxidants (Basel, Switzerland) · 2025Review
- Revealing propionate metabolism-related genes in glioblastoma and investigating their underlying mechanisms.Frontiers in oncology · 2025Article
- Autophagy as a potential therapeutic target in regulating improper cellular proliferation.Frontiers in pharmacology · 2025Review
- Advances in the treatment of glioma-related signaling pathways and mechanisms by metformin.Frontiers in oncology · 2025Review
- Review
- SignalingProfiler 2.0 a network-based approach to bridge multi-omics data to phenotypic hallmarks.NPJ systems biology and applications · 2024Article
- Glycative stress as a cause of macular degeneration.Progress in retinal and eye research · 2024Review
- Phenformin activates ER stress to promote autophagic cell death via NIBAN1 and DDIT4 in oral squamous cell carcinoma independent of AMPK.International journal of oral science · 2024Article
- Review
- Mechanistic Insights about Sorafenib-, Valproic Acid- and Metformin-Induced Cell Death in Hepatocellular Carcinoma.International journal of molecular sciences · 2024Review
- Exploiting gender-based biomarkers and drug targets: advancing personalized therapeutic strategies in hepatocellular carcinoma.Frontiers in pharmacology · 2024Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMetformin may exert the anticancer effect on multiple types of cancers and some potential mechanisms have been suggested. Our study was designed to determine the effect of metformin on the cell autophagy and autophagic flux via the AMPK-mTOR signaling pathway in human hepatocellular carcinoma (HCC) cells.
methodsMHCC97H and HepG2 cell lines were cultured and treated without and with metformin at various concentrations (2, 5, 10 and 20 mM) for 48 h. Then, 10 mM was determined as the optimal concentration and the HCC cells were treated with metformin for 12, 24, 48, and 72 h. MTT assay was used to assess the cell viability and Western blotting was used to determine the expression of proteins (LC3-II, p62, phospho-AMPKα, phospho-mTOR, mTOR, phospho-p70 S6 Kinase, p70 S6 Kinase, PARP1, Caspase-9 and Caspase-3). Autophagy inhibitor 3-methyladenine, EGFP-LC3 and mCherry-GFP-LC3B plasmid transfection were used for further study.
resultsMetformin inhibited significantly the viability of MHCC97H and HepG2 cells in a dose- and time-dependent manner. For the apoptotic properties, activation of Caspase-9 and Caspase-3 and PARP cleavage were not observed after treatment with metformin. MHCC97H cells were transfected with a EGFP-LC3 plasmid and treatment with metformin could lead to the increased level of LC3-II and decreased level of p62. In metformin-induced autophagy, AMPK expression was activated, and the phosphorylation levels of mTOR and p70 S6 Kinase were inhibited. Metformin treatment and mCherry-GFP-LC3B plasmid transfection showed that metformin could induce the autophagic flux. 3-Methyladenine (3-MA) partly abolished this effect.
conclusionMetformin could induce the autophagy, autophagic flux, and activate the AMPK-mTOR signaling pathway in human HCC 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.