ArticleOncotarget2016
Metformin increases PDH and suppresses HIF-1α under hypoxic conditions and induces cell death in oral squamous cell carcinoma.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.
- Effects of metformin on head and neck cancer: an umbrella review.BMC cancer · 2026Pooled it
- Mitochondrial-targeted therapeutics in oral squamous cell carcinoma: molecular and therapeutic implications.Frontiers in medicine · 2026Review
- Biological Anti-Tumoral Mechanisms of Metformin in Head and Neck Squamous Cell Carcinomas: A Systematic Review.Journal of clinical medicine · 2025Review
- Effect of metformin on hypoxia-associated gene expression in oral cavity squamous cell carcinoma in non-diabetic patients - a prospective window of opportunity study.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2025Article
- Article
- Metformin Treatment Is Not Associated with Altered PD-L1 Expression in Diabetic Patients with Oral Squamous Cell Carcinoma.Journal of clinical medicine · 2024Article
- The mechanisms of action of metformin on head and neck cancer in the pre-clinical setting: a scoping review.Frontiers in oncology · 2024Article
- Overexpression of hypoxia-inducible factor-1α in hidradenitis suppurativa: the link between deviated immunity and metabolism.Archives of dermatological research · 2023Article
- Action Mechanism of Metformin and Its Application in Hematological Malignancy Treatments: A Review.Biomolecules · 2023Review
- Effect of low-level light therapy before radiotherapy in oral squamous cell carcinoma: An in vitro study.Lasers in medical science · 2022Article
- Photodynamic therapy mediated by nanoparticles Aluminum Chloro Phthalocyanine in oral squamous carcinoma cells.Lasers in medical science · 2022Article
- Targeting the Interplay between Cancer Metabolic Reprogramming and Cell Death Pathways as a Viable Therapeutic Path.Biomedicines · 2021Review
- Integrated or Independent Actions of Metformin in Target Tissues Underlying Its Current Use and New Possible Applications in the Endocrine and Metabolic Disorder Area.International journal of molecular sciences · 2021Review
- Article
- Acute oral treatment with resveratrol and Lactococcus Lactis Subsp. Lactis decrease body weight and improve liver proinflammatory markers in C57BL/6 mice.Molecular biology reports · 2021Article
- Intersecting Mechanisms of Hypoxia and Prostaglandin E2-Mediated Inflammation in the Comparative Biology of Oral Squamous Cell Carcinoma.Frontiers in oncology · 2021Review
- The key role of Warburg effect in SARS-CoV-2 replication and associated inflammatory response.Biochimie · 2021Review
- Factors leading to high morbidity and mortality of COVID-19 in patients with type 2 diabetes.Journal of diabetes · 2020Review
- Review
- A new aspect of an old friend: the beneficial effect of metformin on anti-tumor immunity.BMB reports · 2020Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMetformin is a biguanide, belonging to the oral hypoglycemic agents and is a widely used in the treatment of type 2 diabetes. Evidence indicate that Metformin inhibits cell proliferation in several human cancers and inhibits the Warburg phenomenon in tumor cells.
resultsLow PDH levels were observed in OSCC, and Metformin promotes an increase in PDH levels in hypoxic conditions. Metformin also reduced HIF-1α mRNA and protein levels. Metformin demonstrated antiproliferative effects, inhibited migration, increased the number of apoptotic cells and increased the transcription of caspase 3.
objectiveThe present study aims to explore the effects of Metformin in hypoxic conditions. Specifically, we focused on pyruvate dehydrogenase (PDH), (hypoxia-inducible factor 1α) HIF-1α levels and the oral squamous cell carcinoma (OSCC) cell phenotype. Additionally, we also investigated a theoretical consequence of Metformin treatment.
methodsPDH levels in patients with OSCC and oral dysplasia were evaluated. Metformin was administered in vitro to test the effect of Metformin under hypoxic conditions. The results were complemented by Bioinformatics analyses.
conclusionsIn conclusion, our current findings show that Metformin reduces HIF-1α gene expression and increases PDH expression. Metformin inhibits cell proliferation and migration in the OSCC cell line model. Additionally, Metformin enhances the number of apoptotic cells and caspase 3 levels. Interestingly enough, Metformin did not increase the mutant p53 levels under hypoxic conditions.
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