ArticleJournal of experimental & clinical cancer research : CR2024
Targeting cancer stem cell OXPHOS with tailored ruthenium complexes as a new anti-cancer strategy.
Article in Journal of experimental & clinical cancer research : CR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Liposome-mediated delivery of a ruthenium-based metallodrug to overcome cisplatin resistance in osteosarcoma.Drug delivery · 2026Article
- Chemical Stabilization and Transformation of Schiff Base Scaffold: A Path toward Superior Platinum-Based Anti-Cancer Stem Cell Drugs.Journal of medicinal chemistry · 2026Article
- Platelet-derived mitochondrial transfer in cancer metastasis: mechanisms, functional consequences, and translational opportunities.Clinical & experimental metastasis · 2026Review
- 17-DMAG-Loaded HER2-Targeted Extracellular Vesicles Induce PARP/Caspase3-Mediated Apoptosis in Gastric Carcinoma.International journal of molecular sciences · 2026Article
- Mitochondrial transfer between tumor and immune cells: a nexus of metabolic adaptation and immune dysfunction.Biomarker research · 2026Review
- NDUFS1-Mediated Mitochondrial Complex I Activity Maintains Pancreatic Cancer Stemness by Promoting PAX2 Hypomethylation.MedComm · 2026Article
- Absolute dynamic and relative static: the relationship of glycolysis and OXPHOS in cancer development.Cell death discovery · 2026Review
- Chlorogenic acid promotes mtDNA leakage to enhance cGAS-STING induced anti-tumor immunity via ATF5-mtHSP70-TFAM system.International journal of biological sciences · 2026Article
- Preclinical Trials of Cancer Stem Cells Targeted by Metal-Based Coordination Complexes: A Systematic Review.Pharmaceutics · 2025Review
- Role of mitochondria in physiological activities, diseases, and therapy.Molecular biomedicine · 2025Review
- The Warburg hypothesis and the emergence of the mitochondrial metabolic theory of cancer.Journal of bioenergetics and biomembranes · 2025Review
- Metabolic plasticity in pancreatic cancer: The mitochondrial connection.Molecular metabolism · 2025Review
- Reprogramming of glucose metabolism in pancreatic cancer: mechanisms, implications, and therapeutic perspectives.Frontiers in immunology · 2025Review
- Reprogramming tumor-associated macrophages with lipid nanosystems reduces PDAC tumor burden and liver metastasis.Journal of nanobiotechnology · 2024Article
- Selective metabolic regulations by p53 mutant variants in pancreatic cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- Altered metabolism in cancer: insights into energy pathways and therapeutic targets.Molecular cancer · 2024Review
- Emerging mechanisms and promising approaches in pancreatic cancer metabolism.Cell death & disease · 2024Review
- Article
- Ru(II)-based complexes containing 2-thiouracil derivatives suppress liver cancer stem cells by targeting NF-κB and Akt/mTOR signaling.Cell death discovery · 2024Article
- Platinum iodido drugs show potential anti-tumor activity, affecting cancer cell metabolism and inducing ROS and senescence in gastrointestinal cancer cells.Communications biology · 2024Article
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Authors and funding
29 authors at 10 institutions in 3 countries.
Funding
Abstract
backgroundPrevious studies by our group have shown that oxidative phosphorylation (OXPHOS) is the main pathway by which pancreatic cancer stem cells (CSCs) meet their energetic requirements; therefore, OXPHOS represents an Achille's heel of these highly tumorigenic cells. Unfortunately, therapies that target OXPHOS in CSCs are lacking.
methodsThe safety and anti-CSC activity of a ruthenium complex featuring bipyridine and terpyridine ligands and one coordination labile position (Ru1) were evaluated across primary pancreatic cancer cultures and in vivo, using 8 patient-derived xenografts (PDXs). RNAseq analysis followed by mitochondria-specific molecular assays were used to determine the mechanism of action.
resultsWe show that Ru1 is capable of inhibiting CSC OXPHOS function in vitro, and more importantly, it presents excellent anti-cancer activity, with low toxicity, across a large panel of human pancreatic PDXs, as well as in colorectal cancer and osteosarcoma PDXs. Mechanistic studies suggest that this activity stems from Ru1 binding to the D-loop region of the mitochondrial DNA of CSCs, inhibiting OXPHOS complex-associated transcription, leading to reduced mitochondrial oxygen consumption, membrane potential, and ATP production, all of which are necessary for CSCs, which heavily depend on mitochondrial respiration.
conclusionsOverall, the coordination complex Ru1 represents not only an exciting new anti-cancer agent, but also a molecular tool to dissect the role of OXPHOS in CSCs. Results indicating that the compound is safe, non-toxic and highly effective in vivo are extremely exciting, and have allowed us to uncover unprecedented mechanistic possibilities to fight different cancer types based on targeting CSC OXPHOS.
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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.