ArticleOncotarget2019
Synergistic inhibition of tumor cell proliferation by metformin and mito-metformin in the presence of iron chelators.
Article in Oncotarget, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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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
17 citing papers in PubMed, 24 citations in OpenAlex.
- Radiotherapy followed by metformin neoadjuvant therapy drives superior pancreatic cancer ferroptosis and augments anti-tumor immunity.Fundamental research · 2026Article
- Sex-specific mitochondrial dysregulation and metformin response in Wilson disease.Scientific reports · 2026Article
- Mitochondria-targeted metformin analogs activate the ER stress-unfolded protein response pathway to drive apoptosis in pancreatic cancer.Cell death & disease · 2026Article
- Metformin: From Diabetes to Cancer-Unveiling Molecular Mechanisms and Therapeutic Strategies.Biology · 2024Review
- Dexrazoxane inhibits the growth of esophageal squamous cell carcinoma by attenuating SDCBP/MDA-9/syntenin-mediated EGFR-PI3K-Akt pathway activation.Scientific reports · 2024Article
- Genetic mutations affecting mitochondrial function in cancer drug resistance.Genes & genomics · 2023Review
- Mitochondrial Metabolism in Pancreatic Ductal Adenocarcinoma: From Mechanism-Based Perspectives to Therapy.Cancers · 2023Review
- The mechanisms of action of mitochondrial targeting agents in cancer: inhibiting oxidative phosphorylation and inducing apoptosis.Frontiers in pharmacology · 2023Review
- Article
- EPR Investigations to Study the Impact of Mito-Metformin on the Mitochondrial Function of Prostate Cancer Cells.Molecules (Basel, Switzerland) · 2022Article
- Biological Properties of Transition Metal Complexes with Metformin and Its Analogues.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Exploiting the tumor immune microenvironment and immunometabolism using mitochondria-targeted drugs: Challenges and opportunities in racial disparity and cancer outcome research.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Review
- Reactive oxygen species, proinflammatory and immunosuppressive mediators induced in COVID-19: overlapping biology with cancer.RSC chemical biology · 2021Review
- Selective Delivery of Dicarboxylates to Mitochondria by Conjugation to a Lipophilic Cation via a Cleavable Linker.Molecular pharmaceutics · 2020Article
- Mitochondrial Metabolism in PDAC: From Better Knowledge to New Targeting Strategies.Biomedicines · 2020Review
- Complex Mitochondrial Dysfunction Induced by TPPCells · 2020Article
- Metformin Synergistically Enhanced the Antitumor Activity of Celecoxib in Human Non-Small Cell Lung Cancer Cells.Frontiers in pharmacology · 2020Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We demonstrate that combined treatment with metformin (Met) or its mitochondria-targeted analog, mito-metformin (Mito-Met), and various iron chelators synergistically inhibits proliferation of pancreatic and triple-negative breast cancer cells. Previously, we reported that Met (at millimolar levels) and Mito-Met (at micromolar levels) inhibited pancreatic cancer cell proliferation. Inhibition of mitochondrial complex I and mitochondrial oxidative phosphorylation (OXPHOS) through stimulation of mitochondrial redox signaling was proposed as a key mechanism for decreased cancer cell proliferation. Because of its poor bioavailability, the use of Met as a "stand-alone" antitumor drug has been questioned. Iron chelators such as deferasirox (DFX) and dexrazoxane (DXR) exhibit antiproliferative effects in cancer cells. The potency of Met and Mito-Met was synergistically enhanced in the presence of iron chelators, DFX, N,N'-bis(2-hydroxyphenyl)ethylendiamine-N,N'-diacetic acid (HBED), and deferoxamine (DFO). Met, DXR (also ICRF-187), and DFO are FDA-approved drugs for treating diabetes, decreasing the incidence and severity of cardiotoxicity following chemotherapy, and mitigating iron toxicity, respectively. Thus, the synergistic antiproliferative effects of Met and Met analogs and iron chelators may have significant clinical relevance in cancer treatment. These findings may have implications in other OXPHOS-mediated cancer therapies.
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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.