ArticlePloS one2014
Synergistic anti-cancer effect of phenformin and oxamate.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
80 citing papers in PubMed, 149 citations in OpenAlex.
- Phenformin-Induced Apoptosis: A Potential Mechanism for Cervical Cancer Cell Inhibition.International journal of molecular sciences · 2026Article
- Suppression of Tumor Aggression Through Metabolic Reprogramming via Oxamate Targeting LDHA.International journal of molecular sciences · 2026Review
- Mitochondrial dysfunction as a metabolic checkpoint of immunotherapy response in colorectal cancer.Frontiers in immunology · 2026Review
- Article
- Oxidative stress in cancer: from tumor and microenvironment remodeling to therapeutic frontiers.Molecular cancer · 2025Review
- Oxamate suppresses whole-body energy metabolism at rest and during exercise in mice by inhibiting fat oxidation and altering lactate dynamics.Physical activity and nutrition · 2025Article
- Metformin-Induced Apoptosis Is Mediated Through Mitochondrial VDAC1.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Progress in antitumor mechanisms and applications of phenformin (Review).Oncology reports · 2024Review
- Accurate evaluation of drug effect on the LDH activity of live cells: dual measurement of live cell number by fluorescent staining of nucleus and LDH activity by formazan.Analytical sciences : the international journal of the Japan Society for Analytical Chemistry · 2024Article
- Enhancing Urological Cancer Treatment: Leveraging Vasodilator Synergistic Potential with 5-FU for Improved Therapeutic Outcomes.Journal of clinical medicine · 2024Article
- Targeting cancer and immune cell metabolism with the complex I inhibitors metformin and IACS-010759.Molecular oncology · 2024Review
- Discovery of Small Molecule Glycolytic Stimulants for Enhanced ApoE Lipidation in Alzheimer's Disease Cell Model.Pharmaceuticals (Basel, Switzerland) · 2024Article
- The troglitazone derivative EP13 disrupts energy metabolism through respiratory chain complex I inhibition in breast cancer cells and potentiates the antiproliferative effect of glycolysis inhibitors.Cancer cell international · 2024Article
- DeepAEG: a model for predicting cancer drug response based on data enhancement and edge-collaborative update strategies.BMC bioinformatics · 2024Article
- Targeting the lactic acid metabolic pathway for antitumor therapy.Molecular therapy oncolytics · 2023Review
- Oxamate enhances the efficacy of CAR-T therapy against glioblastoma via suppressing ectonucleotidases and CCR8 lactylation.Journal of experimental & clinical cancer research : CR · 2023Article
- Cholesterol reprograms glucose and lipid metabolism to promote proliferation in colon cancer cells.Cancer & metabolism · 2023Article
- Bioenergetic alteration in gastrointestinal cancers: The good, the bad and the ugly.World journal of gastroenterology · 2023Review
- A study of the interaction space of two lactate dehydrogenase isoforms (LDHA and LDHB) and some of their inhibitors using proteochemometrics modeling.BMC chemistry · 2023Article
- A pilot study: Metabolic profiling of plasma and saliva samples from newly diagnosed glioblastoma patients.Cancer medicine · 2023Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Phenformin (phenethylbiguanide; an anti-diabetic agent) plus oxamate [lactate dehydrogenase (LDH) inhibitor] was tested as a potential anti-cancer therapeutic combination. In in vitro studies, phenformin was more potent than metformin, another biguanide, recently recognized to have anti-cancer effects, in promoting cancer cell death in the range of 25 times to 15 million times in various cancer cell lines. The anti-cancer effect of phenformin was related to complex I inhibition in the mitochondria and subsequent overproduction of reactive oxygen species (ROS). Addition of oxamate inhibited LDH activity and lactate production by cells, which is a major side effect of biguanides, and induced more rapid cancer cell death by decreasing ATP production and accelerating ROS production. Phenformin plus oxamate was more effective than phenformin combined with LDH knockdown. In a syngeneic mouse model, phenformin with oxamate increased tumor apoptosis, reduced tumor size and (18)F-fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography compared to control. We conclude that phenformin is more cytotoxic towards cancer cells than metformin. Furthermore, phenformin and oxamate have synergistic anti-cancer effects through simultaneous inhibition of complex I in the mitochondria and LDH in the cytosol, respectively.
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Registered trials
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.