ArticleOncotarget2017
Metformin induces cell cycle arrest at the G1 phase through E2F8 suppression in lung 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, 2 of them syntheses that pooled it.
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Who cites it
24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 41 citations in OpenAlex.
- Carcinogenesis effects of E2F transcription factor 8 (E2F8) in hepatocellular carcinoma outcomes: an integrated bioinformatic report.Bioscience reports · 2020Pooled it
- Meta-Analysis of Microarray Expression Studies on Metformin in Cancer Cell Lines.International journal of molecular sciences · 2019Pooled it
- Metformin's multifaceted role in colorectal cancer: mechanisms of action and synergy with standard treatments.Discover oncology · 2025Review
- Repurposing of Metabolic Drugs Metformin and Simvastatin as an Emerging Class of Cancer Therapeutics.Pharmaceutical research · 2025Review
- Article
- Transcriptomic Profiling for Prognostic Biomarkers in Early-Stage Squamous Cell Lung Cancer (SqCLC).Cancers · 2024Article
- Combination of metformin and gallic acid induces autophagy and apoptosis in human breast cancer cells.Research in pharmaceutical sciences · 2023Article
- Fabricating niosomal-PEG nanoparticles co-loaded with metformin and silibinin for effective treatment of human lung cancer cells.Frontiers in oncology · 2023Article
- Effects of metformin on Sonic hedgehog subgroup medulloblastoma progression:Frontiers in pharmacology · 2022Article
- Review
- Metformin inhibits the proliferation of canine mammary gland tumor cells through the AMPK/AKT/mTOR signaling pathwayOncology letters · 2021Article
- Early 2 factor (E2F) transcription factors contribute to malignant progression and have clinical prognostic value in lower-grade glioma.Bioengineered · 2021Article
- SMAD1 as a biomarker and potential therapeutic target in drug-resistant multiple myeloma.Biomarker research · 2021Article
- Metformin impairs cisplatin resistance effects in A549 lung cancer cells through mTOR signaling and other metabolic pathways.International journal of oncology · 2021Article
- Novel insights into the interaction between long non-coding RNAs and microRNAs in glioma.Molecular and cellular biochemistry · 2021Review
- Incorporation of Sulfonamide Moiety into Biguanide Scaffold Results in Apoptosis Induction and Cell Cycle Arrest in MCF-7 Breast Cancer Cells.International journal of molecular sciences · 2021Article
- Metformin Reduces Histone H3K4me3 at the Promoter Regions of Positive Cell Cycle Regulatory Genes in Lung Cancer Cells.Cancers · 2021Article
- The Effects of NT-1044, a Novel AMPK Activator, on Endometrial Cancer Cell Proliferation, Apoptosis, Cell Stress andFrontiers in oncology · 2021Article
- Article
- Antidiabetic drug metformin affects the developmental competence of cleavage-stage embryos.Journal of assisted reproduction and genetics · 2020Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A target molecule responsible for cell cycle arrest by metformin was discovered using a gene chip array in lung cancer cells and the effect of metformin on E2F8 was assessed. The siRNA-mediated knockdown of E2F8 significantly suppressed G1-S progression while ectopic expression of E2F8 relieved metformin-induced G1 arrest. The mRNA levels of p21 were found to be inversely related to those of E2F8 in lung cancer cells while siRNA-mediated knockdown of p21 partly rescued siE2F8-induced arrest of the cell cycle. Metformin had no effect on degradation of E2F8 mRNA. Activation and inhibition of AMPK by AICAR and Dorsomorphin, respectively, did not affect E2F8 suppression by metformin. The clinical significance of E2F8 was analyzed in The Cancer Genome Atlas (TCGA) data. One hundred six (13%) of 848 TCGA lung cancers overexpressed E2F8 mRNA. The overexpression of E2F8 was associated with poor overall survival (adjusted hazard ratio = 1.58, 95% confidence interval = 1.13-2.22; P = 0.008). The present study suggests that metformin may induce cell cycle arrest at the G1 phase by suppressing E2F8 expression in lung cancer cells. In addition, E2F8 may be associated with poor overall survival in lung cancer patients irrespective of histology.
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Registered trials
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