ArticlePloS one2012
Alterations in cellular energy metabolism associated with the antiproliferative effects of the ATM inhibitor KU-55933 and with metformin.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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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
25 citing papers in PubMed, 37 citations in OpenAlex.
- Exploring SGLT2 Inhibitors' Activity in Breast Cancer: An Overview.Current topics in medicinal chemistry · 2025Review
- Effects of long-term metformin administration associated with high-intensity interval training on physical performance, glycogen concentration, GLUT-4 content, and NMR-based metabolomics in healthy rats.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2024Article
- Unveiling the anticancer effects of SGLT-2i: mechanisms and therapeutic potential.Frontiers in pharmacology · 2024Review
- DNA Ligase 4 Contributes to Cell Proliferation against DNA-PK Inhibition inInternational journal of molecular sciences · 2023Article
- Article
- Effect of Metformin on the Prognosis of Gastric Cancer Patients with Type 2 Diabetes Mellitus: A Meta-Analysis Based on Retrospective Cohort Studies.International journal of endocrinology · 2023Article
- Repurposing metformin for the treatment of gastrointestinal cancer.World journal of gastroenterology · 2021Review
- Phenformin and ataxia-telangiectasia mutated inhibitors synergistically co-suppress liver cancer cell growth by damaging mitochondria.FEBS open bio · 2021Article
- SIRT3, a metabolic target linked to ataxia-telangiectasia mutated (ATM) gene deficiency in diffuse large B-cell lymphoma.Scientific reports · 2020Article
- Article
- ATM is activated by ATP depletion and modulates mitochondrial function through NRF1.The Journal of cell biology · 2019Article
- ATM deficiency promotes progression of CRPC by enhancing Warburg effect.Endocrine-related cancer · 2019Article
- Metformin and blood cancers.Clinics (Sao Paulo, Brazil) · 2018Review
- Review
- Cell specific stress responses of cadmium-induced cytotoxicity.Animal cells and systems · 2017Article
- Article
- The RNA-binding protein HuR is essential for the B cell antibody response.Nature immunology · 2015Article
- Metformin Induces Apoptosis and Downregulates Pyruvate Kinase M2 in Breast Cancer Cells Only When Grown in Nutrient-Poor Conditions.PloS one · 2015Article
- Metformin and phenformin deplete tricarboxylic acid cycle and glycolytic intermediates during cell transformation and NTPs in cancer stem cells.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Growth inhibition of colon cancer cells by compounds affecting AMPK activity.World journal of gastrointestinal oncology · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
KU-55933 is a specific inhibitor of the kinase activity of the protein encoded by Ataxia telangiectasia mutated (ATM), an important tumor suppressor gene with key roles in DNA repair. Unexpectedly for an inhibitor of a tumor suppressor gene, KU-55933 reduces proliferation. In view of prior preliminary evidence suggesting defective mitochondrial function in cells of patients with Ataxia Telangiectasia (AT), we examined energy metabolism of cells treated with KU-55933. The compound increased AMPK activation, glucose uptake and lactate production while reducing mitochondrial membrane potential and coupled respiration. The stimulation of glycolysis by KU-55933 did not fully compensate for the reduction in mitochondrial functions, leading to decreased cellular ATP levels and energy stress. These actions are similar to those previously described for the biguanide metformin, a partial inhibitor of respiratory complex I. Both compounds decreased mitochondrial coupled respiration and reduced cellular concentrations of fumarate, malate, citrate, and alpha-ketogluterate. Succinate levels were increased by KU-55933 levels and decreased by metformin, indicating that the effects of ATM inhibition and metformin are not identical. These observations suggest a role for ATM in mitochondrial function and show that both KU-55933 and metformin perturb the TCA cycle as well as oxidative phosphorylation.
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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.