ArticleInternational journal of cell biology2013
Mitochondrial complex I inhibitors and forced oxidative phosphorylation synergize in inducing cancer cell death.
Article in International journal of cell biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 57 citations in OpenAlex.
- Oxidative Phosphorylation System in Gastric Carcinomas and Gastritis.Oxidative medicine and cellular longevity · 2017Trial
- PSG6: A mitochondrially-targeted gentisic acid derivative exerts antiplatelet action via mitochondrial complex I inhibition.Redox biology · 2026Article
- Modeling Krebs cycle from liver, heart and hepatoma mitochondria, supported Complex I as target for specific inhibition of cancer cell proliferation.Frontiers in oncology · 2025Article
- Article
- Mitochondrial dysfunction at the crossroad of cardiovascular diseases and cancer.Journal of translational medicine · 2023Review
- Counteracting Colon Cancer by Inhibiting Mitochondrial Respiration and Glycolysis with a Selective PKCδ Activator.International journal of molecular sciences · 2023Article
- Alpinumisoflavone Impairs Mitochondrial Respiration via Oxidative Stress and MAPK/PI3K Regulation in Hepatocellular Carcinoma Cells.Antioxidants (Basel, Switzerland) · 2022Article
- An appraisal of the current status of inhibition of glucose transporters as an emerging antineoplastic approach: Promising potential of new pan-GLUT inhibitors.Frontiers in pharmacology · 2022Review
- Elevation of Chemosensitivity of Lung Adenocarcinoma A549 Spheroid Cells by Claudin-2 Knockdown through Activation of Glucose Transport and Inhibition of Nrf2 Signal.International journal of molecular sciences · 2021Article
- Screening for Combination Cancer Therapies With Dynamic Fuzzy Modeling and Multi-Objective Optimization.Frontiers in genetics · 2021Article
- Crizotinib changes the metabolic pattern and inhibits ATP production in A549 non-small cell lung cancer cells.Oncology letters · 2021Article
- Targeting the Mitochondrial Metabolic Network: A Promising Strategy in Cancer Treatment.International journal of molecular sciences · 2020Review
- Review
- Manipulation of Mitochondrial Plasticity Changes the Metabolic Competition Between "Foe" and "Friend" During Tumor Malignant Transformation.Frontiers in oncology · 2020Review
- Metformin sensitizes therapeutic agents and improves outcome in pre-clinical and clinical diffuse large B-cell lymphoma.Cancer & metabolism · 2020Article
- Inhibition of mitochondrial respiration prevents BRAF-mutant melanoma brain metastasis.Acta neuropathologica communications · 2019Article
- Collagen density modulates triple-negative breast cancer cell metabolism through adhesion-mediated contractility.Scientific reports · 2018Article
- HORMAD1 Is a Negative Prognostic Indicator in Lung Adenocarcinoma and Specifies Resistance to Oxidative and Genotoxic Stress.Cancer research · 2018Article
- TheGenes · 2018Review
- AG311, a small molecule inhibitor of complex I and hypoxia-induced HIF-1α stabilization.Cancer letters · 2017Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer cells generally rely mostly on glycolysis rather than oxidative phosphorylation (OXPHOS) for ATP production. In fact, they are particularly sensitive to glycolysis inhibition and glucose depletion. On the other hand mitochondrial dysfunctions, involved in the onset of the Warburg effect, are sometimes also associated with the resistance to apoptosis that characterizes cancer cells. Therefore, combined treatments targeting both glycolysis and mitochondria function, exploiting peculiar tumor features, might be lethal for cancer cells. In this study, we show that glucose deprivation and mitochondrial Complex I inhibitors synergize in inducing cancer cell death. In particular, our results reveal that low doses of Complex I inhibitors, ineffective on immortalized cells and in high glucose growth, become specifically cytotoxic on cancer cells deprived of glucose. Importantly, the cytotoxic effect of the inhibitors on cancer cells is strongly enhanced by forskolin, a PKA pathway activator, that we have previously shown to stimulate OXPHOS. Taken together, we demonstrate that induction in cancer cells of a switch from a glycolytic to a more respirative metabolism, obtained by glucose depletion or mitochondrial activity stimulation, strongly increases their sensitivity to low doses of mitochondrial Complex I inhibitors. Our findings might be a valuable approach to eradicate cancer cells.
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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.