ArticleThe Journal of biological chemistry2013
Reversing the Warburg effect as a treatment for glioblastoma.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 76 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 citations in OpenAlex.
- Repurposing neurological drugs for brain cancer therapeutics: A systematic approach to identify charged molecules for affinity-based local drug delivery systems.International journal of pharmaceutics · 2025Pooled it
- Integrated profiling identifies NCOA3 as a prognostic factor in patients with glioma.Functional & integrative genomics · 2026Article
- Fatty Acid Metabolism Rewires Glioblastoma Progression and Treg-Mediated Immune Resistance.Cancers · 2026Review
- Gut Dysbiosis Serine-Glycine Metabolism and Glioblastoma: Exploring Therapeutic Opportunities.Cancers · 2026Review
- Photodynamic Therapy Combined with Anticancer Drug Therapy in the Treatment of Malignant Neoplasms.Cells · 2026Review
- Defining treatment-resistant brain cancer: Genetic screening to identify oncogene-driven immunomodulation and therapy resistance.Cancer gene therapy · 2026Review
- Metabolic reprogramming and immunosenescence: a new sight for glioma therapy.Frontiers in cell and developmental biology · 2026Review
- C1q drives neural stem cell quiescence by regulating cell cycle and metabolism through BAI1.Nature communications · 2025Article
- Epitranscriptomic analysis reveals clinical and molecular signatures in glioblastoma.Acta neuropathologica communications · 2025Article
- Glioblastoma multiforme: insights into pathogenesis, key signaling pathways, and therapeutic strategies.Molecular cancer · 2025Review
- Spectroscopic Study of Methylene Blue Interaction with Coenzymes and its Effect on Tumor Metabolism.Sovremennye tekhnologii v meditsine · 2025Article
- E2F1-driven CENPM expression promotes glycolytic reprogramming and tumorigenicity in glioblastoma.Cell biology and toxicology · 2024Article
- Amino Acid Deprivation in Glioblastoma: The Role in Survival and the Tumour Microenvironment-A Narrative Review.Biomedicines · 2024Review
- The compartment-specific manipulation of the NADScientific reports · 2024Article
- Deciphering Glioblastoma: Fundamental and Novel Insights into the Biology and Therapeutic Strategies of Gliomas.Current issues in molecular biology · 2024Review
- Glutamate Provides Cytoprotective Effect for Astrocytes Against Ischemic Insult and Promotes Astrogliosis.Aging and disease · 2024Article
- pH-Weighted amine chemical exchange saturation transfer echo planar imaging visualizes infiltrating glioblastoma cells.Neuro-oncology · 2024Article
- Association between glioma and neurodegenerative diseases risk: a two-sample bi-directional Mendelian randomization analysis.Frontiers in neurology · 2024Article
- Role of Glycolytic and Glutamine Metabolism Reprogramming on the Proliferation, Invasion, and Apoptosis Resistance through Modulation of Signaling Pathways in Glioblastoma.International journal of molecular sciences · 2023Review
- Warburg effect-related risk scoring model to assess clinical significance and immunity characteristics of glioblastoma.Cancer medicine · 2023Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
Glioblastoma multiforme (GBM), like most cancers, possesses a unique bioenergetic state of aerobic glycolysis known as the Warburg effect. Here, we documented that methylene blue (MB) reverses the Warburg effect evidenced by the increasing of oxygen consumption and reduction of lactate production in GBM cell lines. MB decreases GBM cell proliferation and halts the cell cycle in S phase. Through activation of AMP-activated protein kinase, MB inactivates downstream acetyl-CoA carboxylase and decreases cyclin expression. Structure-activity relationship analysis demonstrated that toluidine blue O, an MB derivative with similar bioenergetic actions, exerts similar action in GBM cell proliferation. In contrast, two other MB derivatives, 2-chlorophenothiazine and promethazine, exert no effect on cellular bioenergetics and do not inhibit GBM cell proliferation. MB inhibits cell proliferation in both temozolomide-sensitive and -insensitive GBM cell lines. In a human GBM xenograft model, a single daily dosage of MB does not activate AMP-activated protein kinase signaling, and no tumor regression was observed. In summary, the current study provides the first in vitro proof of concept that reversal of Warburg effect might be a novel therapy for GBM.
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What OpenQuestion holds
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.