ArticleiScience2021
Mitochondrial complex I inhibitors suppress tumor growth through concomitant acidification of the intra- and extracellular environment.
Article in iScience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- β3-adrenergic blockade targets fatty acid oxidation to induce ferroptotic vulnerability in pediatric T-ALL.Biology direct · 2026Article
- SUSD2 Promotes Metastasis and Primary Tumor Growth in Pancreatic Cancer Cells via Integrin-FAK Signaling Activation.Cancer science · 2026Article
- Reprogramming oncogenic mitochondria in pancreatic adenocarcinoma through BRD4 inhibition leads to programmed cell death.The Journal of pharmacology and experimental therapeutics · 2025Article
- CDH11 Contributes to Bladder Cancer Progression via Regulation of Mitochondrial Energy Metabolism.Cancer medicine · 2025Article
- Induced mitochondrial deficit by NDUFS3 transient silencing reduces RAB7 expression and causes lysosomal dysfunction in pancreatic cancer cells.Cell communication and signaling : CCS · 2025Article
- Energy metabolism in health and diseases.Signal transduction and targeted therapy · 2025Review
- Selective deficiency of mitochondrial respiratory complex I subunits Ndufs4/6 causes tumor immunogenicity.Nature cancer · 2025Article
- Mitochondrial micro RNAs: Crucial players in carcinogenesis.Oncology research · 2025Review
- Prokaryotic organelle mitochondria drive tumorigenesis: "the original sin".Frontiers in oncology · 2025Review
- Proton-Translocating NADH-Ubiquinone Oxidoreductase: Interaction with Artificial Electron Acceptors, Inhibitors, and Potential Medicines.International journal of molecular sciences · 2024Review
- The Interplay between Autophagy and Mitochondria in Cancer.International journal of molecular sciences · 2024Review
- Active DNA Demethylase, TET1, Increases Oxidative Phosphorylation and Sensitizes Ovarian Cancer Stem Cells to Mitochondrial Complex I Inhibitor.Antioxidants (Basel, Switzerland) · 2024Article
- Complex I activity in hypoxia: implications for oncometabolism.Biochemical Society transactions · 2024Review
- Mitochondrial DNA mutations drive aerobic glycolysis to enhance checkpoint blockade response in melanoma.Nature cancer · 2024Article
- Two new adenopeptins B and C inhibit sphere formation of pancreatic cancer cells.The Journal of antibiotics · 2024Article
- Redox-crippled MitoQ potently inhibits breast cancer and glioma cell proliferation: A negative control for verifying the antioxidant mechanism of MitoQ in cancer and other oxidative pathologies.Free radical biology & medicine · 2023Article
- Viability of HepG2 and MCF-7 cells is not correlated with mitochondrial bioenergetics.Scientific reports · 2023Article
- Metformin and cancer hallmarks: shedding new lights on therapeutic repurposing.Journal of translational medicine · 2023Review
- Genetic mutations affecting mitochondrial function in cancer drug resistance.Genes & genomics · 2023Review
- SRGAP2 controls colorectal cancer chemosensitivity via regulation of mitochondrial complex I activity.Human cell · 2022Article
Corrections and comments
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Authors and funding
25 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The disruption of the tumor microenvironment (TME) is a promising anti-cancer strategy, but its effective targeting for solid tumors remains unknown. Here, we investigated the anti-cancer activity of the mitochondrial complex I inhibitor intervenolin (ITV), which modulates the TME independent of energy depletion. By modulating lactate metabolism, ITV induced the concomitant acidification of the intra- and extracellular environment, which synergistically suppressed S6K1 activity in cancer cells through protein phosphatase-2A-mediated dephosphorylation via G-protein-coupled receptor(s). Other complex I inhibitors including metformin and rotenone were also found to exert the same effect through an energy depletion-independent manner as ITV. In mouse and patient-derived xenograft models, ITV was found to suppress tumor growth and its mode of action was further confirmed. The TME is usually acidic owing to glycolytic cancer cell metabolism, and this condition is more susceptible to complex I inhibitors. Thus, we have demonstrated a potential treatment strategy for solid tumors.
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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.