ArticleScientific reports2021
Metformin-induced ROS upregulation as amplified by apigenin causes profound anticancer activity while sparing normal cells.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Necroptosis in pancreatic cancer: Molecular mechanisms and therapeutic implications.Apoptosis : an international journal on programmed cell death · 2026Pooled it
- Metformin induces ferroptosis associated with lipidomic remodeling in AML.Blood advances · 2026Article
- Metformin Suppresses Glioblastoma Tumor Growth and Progression Through the AMPK/FoxO3a/Survivin Axis.Cells · 2026Article
- AMPK phosphorylates WIP1 to promote DNA repair and radioresistance in cancer cells.Cell death & disease · 2025Article
- Reversal of metformin's anti-proliferative effect in fission yeastnpj metabolic health and disease · 2025Article
- Effect of metformin on cell proliferation and apoptosis in steatosis HepG2 cell model.Northern clinics of Istanbul · 2025Article
- Non-coding RNAs as potential targets in metformin therapy for cancer.Cancer cell international · 2024Review
- Metformin-induced oxidative stress inhibits LNCaP prostate cancer cell survival.Molecular biology reports · 2024Article
- Apigenin: Molecular Mechanisms and Therapeutic Potential against Cancer Spreading.International journal of molecular sciences · 2024Review
- Demonstrating drug treatment efficacies by monitoring superoxide dynamics in human lung cancer cells with time-lapse fluorescence microscopy.Journal of biophotonics · 2024Article
- LncRNAs as nodes for the cross-talk between autophagy and Wnt signaling in pancreatic cancer drug resistance.International journal of biological sciences · 2024Review
- Combination of metformin/efavirenz/fluoxetine exhibits profound anticancer activity via a cancer cell-specific ROS amplification.Cancer biology & therapy · 2023Article
- Inflammatory macrophages reprogram to immunosuppression by reducing mitochondrial translation.Nature communications · 2023Article
- The Role of Oxidative Stress in Trisomy 21 Phenotype.Cellular and molecular neurobiology · 2023Review
- Synergism Antiproliferative Effects of Apigenin and Naringenin in NSCLC Cells.Molecules (Basel, Switzerland) · 2023Article
- Article
- Metformin protects trabecular meshwork against oxidative injury via activating integrin/ROCK signals.eLife · 2023Article
- Metformin is a metabolic modulator and radiosensitiser in rectal cancer.Frontiers in oncology · 2023Article
- Role of Induced Programmed Cell Death in the Chemopreventive Potential of Apigenin.International journal of molecular sciences · 2022Review
- Metformin Intervention-A Panacea for Cancer Treatment?Cancers · 2022Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metformin increased cellular ROS levels in AsPC-1 pancreatic cancer cells, with minimal effect in HDF, human primary dermal fibroblasts. Metformin reduced cellular ATP levels in HDF, but not in AsPC-1 cells. Metformin increased AMPK, p-AMPK (Thr172), FOXO3a, p-FOXO3a (Ser413), and MnSOD levels in HDF, but not in AsPC-1 cells. p-AMPK and p-FOXO3a also translocated from the cytosol to the nucleus by metformin in HDF, but not in AsPC-1 cells. Transfection of si-FOXO3a in HDF increased ROS levels, while wt-FOXO3a-transfected AsPC-1 cells decreased ROS levels. Metformin combined with apigenin increased ROS levels dramatically and decreased cell viability in various cancer cells including AsPC-1 cells, with each drug used singly having a minimal effect. Metformin/apigenin combination synergistically decreased mitochondrial membrane potential in AsPC-1 cells but to a lesser extent in HDF cells. Metformin/apigenin combination in AsPC-1 cells increased DNA damage-, apoptosis-, autophagy- and necroptosis-related factors, but not in HDF cells. Oral administration with metformin/apigenin caused dramatic blocks tumor size in AsPC-1-xenografted nude mice. Our results suggest that metformin in cancer cells differentially regulates cellular ROS levels via AMPK-FOXO3a-MnSOD pathway and combination of metformin/apigenin exerts anticancer activity through DNA damage-induced apoptosis, autophagy and necroptosis by cancer cell-specific ROS amplification.
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