ArticlePloS one2016
Combined Treatment of MCF-7 Cells with AICAR and Methotrexate, Arrests Cell Cycle and Reverses Warburg Metabolism through AMP-Activated Protein Kinase (AMPK) and FOXO1.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Pooled it
- Targeting AMPK for Cancer Therapy: Metabolic Reprogramming as a Therapeutic Strategy.Oncology research · 2025Review
- Cuproptosis: a promising new target for breast cancer therapy.Cancer cell international · 2024Review
- Metabolic Fingerprinting of Blood and Urine of Dairy Cows Affected by Bovine Leukemia Virus: A Mass Spectrometry Approach.Metabolites · 2024Article
- AMPK-a key factor in crosstalk between tumor cell energy metabolism and immune microenvironment?Cell death discovery · 2024Review
- FoxO1 promotes ovarian cancer by increasing transcription and METTL14-mediated mCancer science · 2024Article
- Targeting the Warburg effect: A revisited perspective from molecular mechanisms to traditional and innovative therapeutic strategies in cancer.Acta pharmaceutica Sinica. B · 2024Review
- Novel Anti-Cancer Products Targeting AMPK: Natural Herbal Medicine against Breast Cancer.Molecules (Basel, Switzerland) · 2023Review
- The role of AMPK in cancer metabolism and its impact on the immunomodulation of the tumor microenvironment.Frontiers in immunology · 2023Review
- ATP Mimetic Attack on the Nucleotide-Binding Domain to Overcome ABC Transporter Mediated Chemoresistance.ACS medicinal chemistry letters · 2022Article
- Tissue Transglutaminase Knock-Out Preadipocytes and Beige Cells of Epididymal Fat Origin Possess Decreased Mitochondrial Functions Required for Thermogenesis.International journal of molecular sciences · 2022Article
- Article
- The involvement of oncobiosis and bacterial metabolite signaling in metastasis formation in breast cancer.Cancer metastasis reviews · 2021Review
- 6-Shogaol Antagonizes the Adipocyte-Conditioned Medium-Initiated 5-Fluorouracil Resistance in Human Colorectal Cancer Cells through Controlling the SREBP-1 Level.Life (Basel, Switzerland) · 2021Article
- Ruthenium Half-Sandwich Type Complexes with Bidentate Monosaccharide Ligands Show Antineoplastic Activity in Ovarian Cancer Cell Models through Reactive Oxygen Species Production.International journal of molecular sciences · 2021Article
- circEVI5 acts as a miR-4793-3p sponge to suppress the proliferation of gastric cancer.Cell death & disease · 2021Article
- Cell fusion enhances energy metabolism of mesenchymal tumor hybrid cells to sustain their proliferation and invasion.BMC cancer · 2021Article
- Article
- Review
- Circular RNAs Regulate Glucose Metabolism in Cancer Cells.OncoTargets and therapy · 2021Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer cells are characterized by metabolic alterations, namely, depressed mitochondrial oxidation, enhanced glycolysis and pentose phosphate shunt flux to support rapid cell growth, which is called the Warburg effect. In our study we assessed the metabolic consequences of a joint treatment of MCF-7 breast cancer cells with AICAR, an inducer of AMP-activated kinase (AMPK) jointly with methotrexate (MTX), a folate-analog antimetabolite that blunts de novo nucleotide synthesis. MCF7 cells, a model of breast cancer cells, were resistant to the individual application of AICAR or MTX, however combined treatment of AICAR and MTX reduced cell proliferation. Prolonged joint application of AICAR and MTX induced AMPK and consequently enhanced mitochondrial oxidation and reduced the rate of glycolysis. These metabolic changes suggest an anti-Warburg rearrangement of metabolism that led to the block of the G1/S and the G2/M transition slowing down cell cycle. The slowdown of cell proliferation was abolished when mitotropic transcription factors, PGC-1α, PGC-1β or FOXO1 were silenced. In human breast cancers higher expression of AMPKα and FOXO1 extended survival. AICAR and MTX exerts similar additive antiproliferative effect on other breast cancer cell lines, such as SKBR and 4T1 cells, too. Our data not only underline the importance of Warburg metabolism in breast cancer cells but nominate the AICAR+MTX combination as a potential cytostatic regime blunting Warburg metabolism. Furthermore, we suggest the targeting of AMPK and FOXO1 to combat breast cancer.
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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 Socratic graph.