ArticleScientific reports2020
Methotrexate elicits pro-respiratory and anti-growth effects by promoting AMPK signaling.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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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
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- Therapeutic Potential of Stem Cells in the Treatment and Management of Immunomodulatory Disorders.Current pharmaceutical design · 2026Pooled it
- Maternal One-Carbon Supplement Reduced the Risk of Non-Alcoholic Fatty Liver Disease in Male Offspring.Nutrients · 2022Article
- Glutathione levels are associated with methotrexate resistance in acute lymphoblastic leukemia cell lines.Frontiers in oncology · 2022Article
- Mesenchymal Stem Cell-Based Therapy for Rheumatoid Arthritis.International journal of molecular sciences · 2021Review
- Metformin sensitises hepatocarcinoma cells to methotrexate by targeting dihydrofolate reductase.Cell death & disease · 2021Article
- Review
- Juvenile Dermatomyositis: New Clues to Diagnosis and Therapy.Current treatment options in rheumatology · 2021Article
- Mitochondria as Key Players in the Pathogenesis and Treatment of Rheumatoid Arthritis.Frontiers in immunology · 2021Review
- Transcriptomics Analysis and Re-sequencing Reveal the Mechanism Underlying the Thermotolerance of an Artificial Selection Population of the Pacific Oyster.Frontiers in physiology · 2021Article
- Diverse Inhibitors of De Novo Purine Synthesis Promote AICAR-Induced AMPK Activation and Glucose Uptake in L6 Myotubes.BioFactors (Oxford, England)Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
One-carbon metabolism fuels the high demand of cancer cells for nucleotides and other building blocks needed for increased proliferation. Although inhibitors of this pathway are widely used to treat many cancers, their global impact on anabolic and catabolic processes remains unclear. Using a combination of real-time bioenergetics assays and metabolomics approaches, we investigated the global effects of methotrexate on cellular metabolism. We show that methotrexate treatment increases the intracellular concentration of the metabolite AICAR, resulting in AMPK activation. Methotrexate-induced AMPK activation leads to decreased one-carbon metabolism gene expression and cellular proliferation as well as increased global bioenergetic capacity. The anti-proliferative and pro-respiratory effects of methotrexate are AMPK-dependent, as cells with reduced AMPK activity are less affected by methotrexate treatment. Conversely, the combination of methotrexate with the AMPK activator, phenformin, potentiates its anti-proliferative activity in cancer cells. These data highlight a reciprocal effect of methotrexate on anabolic and catabolic processes and implicate AMPK activation as a metabolic determinant of methotrexate response.
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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.