ArticleOxidative medicine and cellular longevity2019
Metformin Suppresses Self-Renewal Ability and Tumorigenicity of Osteosarcoma Stem Cells via Reactive Oxygen Species-Mediated Apoptosis and Autophagy.
Article in Oxidative medicine and cellular longevity, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 50 citations in OpenAlex.
- p53 and p21 Status Influences Cellular Response to Metformin inCurrent issues in molecular biology · 2026Article
- Metformin Redirects Autophagy from Bulk Turnover to Mitochondrial Clearance.bioRxiv : the preprint server for biology · 2026Article
- Hepatocellular carcinoma stem cells: the current state of small molecule-based inhibitors.Cell death & disease · 2025Review
- Antifungal effects of Metformin against Candida albicans by autophagy regulation.Journal of microbiology (Seoul, Korea) · 2025Article
- Repurposing of Metabolic Drugs Metformin and Simvastatin as an Emerging Class of Cancer Therapeutics.Pharmaceutical research · 2025Review
- Autophagy and cancer therapy.Cancer letters · 2024Review
- Non-coding RNAs as potential targets in metformin therapy for cancer.Cancer cell international · 2024Review
- Mitochondria: a new intervention target for tumor invasion and metastasis.Molecular medicine (Cambridge, Mass.) · 2024Review
- Drug repurposing: A novel strategy to target cancer stem cells and therapeutic resistance.Genes & diseases · 2024Review
- p66Shc deficiency in CLL cells enhances PD-L1 expression and suppresses immune synapse formation.Frontiers in cell and developmental biology · 2024Article
- [Research Progress on the Combination Therapy of EGFR-TKIs and Metformin in Acquired Resistance to EGFR-TKIs in Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2023Article
- Autophagy Modulation as a Potential Therapeutic Strategy in Osteosarcoma: Current Insights and Future Perspectives.International journal of molecular sciences · 2023Review
- Crosstalk between autophagy and CSCs: molecular mechanisms and translational implications.Cell death & disease · 2023Review
- Metformin and cancer hallmarks: shedding new lights on therapeutic repurposing.Journal of translational medicine · 2023Review
- Redox Signaling Modulates Activity of Immune Checkpoint Inhibitors in Cancer Patients.Biomedicines · 2023Review
- Active targeting schemes for nano-drug delivery systems in osteosarcoma therapeutics.Journal of nanobiotechnology · 2023Review
- Metformin impairs trophoblast metabolism and differentiation in a dose-dependent manner.Frontiers in cell and developmental biology · 2023Article
- Genetic Alterations and Deregulation of Hippo Pathway as a Pathogenetic Mechanism in Bone and Soft Tissue Sarcoma.Cancers · 2022Review
- Chemoresistance-Related Stem Cell Signaling in Osteosarcoma and Its Plausible Contribution to Poor Therapeutic Response: A Discussion That Still Matters.International journal of molecular sciences · 2022Review
- Eugenol Attenuates Transmissible Gastroenteritis Virus-Induced Oxidative Stress and Apoptosis Via ROS-NRF2-ARE Signaling.Antioxidants (Basel, Switzerland) · 2022Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteosarcoma is the most frequently diagnosed primary malignant bone sarcoma in children and adolescents. Recent studies have shown that cancer stem cells (CSCs), a cluster of tumor cells with the ability to self-renew, play an essential role in tumor recurrence and metastasis. Thus, it is necessary to develop therapeutic strategies specifically targeting CSCs. Metformin, the first-line drug for type 2 diabetes, exhibits antineoplastic activities in various kinds of tumors. New evidence has suggested that metformin may target CSCs and prevent their recurrence. However, the underlying specific mechanisms remain unclear. In this study, we found that metformin significantly suppressed the self-renewal ability of osteosarcoma stem cells (OSCs) and induced G0/G1 phase arrest by blocking the activity of cyclin-dependent kinases. Furthermore, metformin induced apoptosis through a mitochondria-dependent pathway, leading to the collapse of the mitochondrial transmembrane potential and the production of reactive oxygen species (ROS). Importantly, metformin acted directly on the mitochondria, which resulted in decreased ATP synthesis. This change allowed access to the downstream AMPK kinase, and the activation of AMPK led to the reversal of the mTOR pathway, triggering autophagy. Particularly, metformin-mediated autophagy disturbed the homeostasis of stemness and pluripotency in the OSCs. Additionally, our mouse xenograft model confirmed the potential therapeutic use of metformin in targeting OSCs. In conclusion, our findings suggest that metformin suppresses the self-renewal ability and tumorigenicity of OSCs via ROS-mediated apoptosis and autophagy.
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