ArticleNeuro-oncology2018
Regulation of bioenergetics through dual inhibition of aldehyde dehydrogenase and mitochondrial complex I suppresses glioblastoma tumorspheres.
Article in Neuro-oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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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
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.
- Mechanisms of imipridones in targeting mitochondrial metabolism in cancer cells.Neuro-oncology · 2021Pooled it
- NF-κB-active tumors with matrix CAFs and suppressive immunity as key resistance mechanisms to chemoradiation in rectal cancer.Experimental & molecular medicine · 2026Article
- Primary glioma cell culture: from monolayer to organoids.Protoplasma · 2026Review
- Pharmacological transglutaminase 2 inhibition enhances temozolomide response in patient-derived glioblastoma tumorspheres.Journal of neuro-oncology · 2026Article
- ATP release mediated by TRPM3 enhances invasion in glioblastoma.Animal cells and systems · 2026Article
- Differential Expression of One-Carbon Pathway Enzyme ALDH1L1 Is Linked to Tumorigenicity of Low-Grade Bladder Cancer Cells Through Metabolic Reprogramming.Cancer medicine · 2025Article
- Probing the metabolic regulator and candidate tumor suppressor ALDH1L1 as a target for non-small cell lung cancer gene therapy.Molecular therapy. Oncology · 2025Article
- Focused ultrasound-mediated temozolomide delivery into intact blood-brain barrier tissue improves survival in patient-derived xenograft model of glioblastoma.Fluids and barriers of the CNS · 2025Article
- Tumor microenvironment-preserving gliosarcoma organoids as an in vitro preclinical platform: a comparative analysis with glioblastoma models.Journal of translational medicine · 2025Article
- Comparison of the biological characteristics of glioblastoma tumorspheres obtained from fresh and cryopreserved glioblastoma tissues.Journal of neuro-oncology · 2025Article
- Tumor suppressive effect of low-frequency repetitive transcranial magnetic stimulation on glioblastoma progression.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- N-phenylmaleimide induces bioenergetic switch and suppresses tumor growth in glioblastoma tumorspheres by inhibiting SLC25A11.Cancer cell international · 2025Article
- Synergistic combination of perphenazine and temozolomide suppresses patient-derived glioblastoma tumorspheres.Neuro-oncology · 2025Article
- Progress in antitumor mechanisms and applications of phenformin (Review).Oncology reports · 2024Review
- Targeting Retinaldehyde Dehydrogenases to Enhance Temozolomide Therapy in Glioblastoma.International journal of molecular sciences · 2024Article
- Visualizing cancer-originating acetate uptake through monocarboxylate transporter 1 in reactive astrocytes in the glioblastoma tumor microenvironment.Neuro-oncology · 2024Article
- Comparison of Glioblastoma Cell Culture Platforms Based on Transcriptional Similarity with Paired Tissue.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Classification of IDH wild-type glioblastoma tumorspheres into low- and high-invasion groups based on their transcriptional program.British journal of cancer · 2023Article
- Human Aldehyde Dehydrogenases: A Superfamily of Similar Yet Different Proteins Highly Related to Cancer.Cancers · 2023Review
- C5α secreted by tumor mesenchymal stem-like cells mediates resistance to 5-aminolevulinic acid-based photodynamic therapy against glioblastoma tumorspheres.Journal of cancer research and clinical oncology · 2023Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Targeted approaches for treating glioblastoma (GBM) attempted to date have consistently failed, highlighting the imperative for treatment strategies that operate on different mechanistic principles. Bioenergetics deprivation has emerged as an effective therapeutic approach for various tumors. We have previously found that cancer cells preferentially utilize cytosolic NADH supplied by aldehyde dehydrogenase (ALDH) for ATP production through oxidative phosphorylation (OxPhos). This study is aimed at examining therapeutic responses and underlying mechanisms of dual inhibition of ALDH and OxPhos against GBM. Methods: For inhibition of ALDH and OxPhos, the corresponding inhibitors, gossypol and phenformin were used. Biological functions, including ATP levels, stemness, invasiveness, and viability, were evaluated in GBM tumorspheres (TSs). Gene expression profiles were analyzed using microarray data. In vivo anticancer efficacy was examined in a mouse orthotopic xenograft model. Results: Combined treatment of GBM TSs with gossypol and phenformin significantly reduced ATP levels, stemness, invasiveness, and cell viability. Consistently, this therapy substantially decreased expression of genes associated with stemness, mesenchymal transition, and invasion in GBM TSs. Supplementation of ATP using malate abrogated these effects, whereas knockdown of ALDH1L1 mimicked them, suggesting that disruption of ALDH-mediated ATP production is a key mechanism of this therapeutic combination. In vivo efficacy confirmed remarkable therapeutic responses to combined treatment with gossypol and phenformin. Conclusion: Our findings suggest that dual inhibition of tumor bioenergetics is a novel and effective strategy for the treatment of GBM.
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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 OpenQuestion graph.