ArticleScientific reports2014
Extracellular iron diminishes anticancer effects of vitamin C: an in vitro study.
Article in Scientific reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 66 citations in OpenAlex.
- OCancer cell · 2017Trial
- Review
- Article
- Iron-oxide nanoparticles selectively enhance the toxicity of pharmacological ascorbate through hydrogen peroxide-dependent DNA damage in non-small cell lung cancer (NSCLC).Free radical biology & medicine · 2025Article
- Mapping the genetic landscape of iron metabolism uncovers the SETD2 methyltransferase as a modulator of iron flux.Science advances · 2025Article
- Article
- Analysis of High-Dose Ascorbate-Induced Cytotoxicity in Human Glioblastoma Cells and the Role of Dehydroascorbic Acid and Iron.Antioxidants (Basel, Switzerland) · 2024Article
- Redox-active vitamin C suppresses human osteosarcoma growth by triggering intracellular ROS-iron-calcium signaling crosstalk and mitochondrial dysfunction.Redox biology · 2024Article
- Iron promotes glycolysis to drive colon tumorigenesis.Biochimica et biophysica acta. Molecular basis of disease · 2023Article
- Review
- Relevant Membrane Transport Proteins as Possible Gatekeepers for Effective Pharmacological Ascorbate Treatment in Cancer.Antioxidants (Basel, Switzerland) · 2023Review
- Exogenous iron impairs the anti-cancer effect of ascorbic acid both in vitro and in vivo.Journal of advanced research · 2023Article
- Selenium Modulates Cancer Cell Response to Pharmacologic Ascorbate.Cancer research · 2022Article
- High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer.Journal of experimental & clinical cancer research : CR · 2021Review
- Machine Learning of Bacterial Transcriptomes Reveals Responses Underlying Differential Antibiotic Susceptibility.mSphere · 2021Article
- New Insights into Red Blood Cell Microcytosis upon mTOR Inhibitor Administration.International journal of molecular sciences · 2021Article
- Starch-Based Carbon Dots for Nitrite and Sulfite Detection.Frontiers in chemistry · 2021Article
- The Double-Faced Role of Nitric Oxide and Reactive Oxygen Species in Solid Tumors.Antioxidants (Basel, Switzerland) · 2020Review
- Pro- and Antioxidant Effects of Vitamin C in Cancer in correspondence to Its Dietary and Pharmacological Concentrations.Oxidative medicine and cellular longevity · 2019Review
- Noninvasive evaluation ofScientific reports · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In vitro studies have shown that hydrogen peroxide (H2O2) produced by high-concentration ascorbate and cell culture medium iron efficiently kills cancer cells. This provided the rationale for clinical trials of high-dose intravenous ascorbate-based treatment for cancer. A drawback in all the in vitro studies was their failure to take into account the in vivo concentration of iron to supplement cell culture media which are characterized by low iron content. Here we showed, using two prostate cancer cell lines (LNCaP and PC-3) and primary astrocytes, that the anticancer/cytotoxic effects of ascorbate are completely abolished by iron at physiological concentrations in cell culture medium and human plasma. A detailed examination of mechanisms showed that iron at physiological concentrations promotes both production and decomposition of H2O2. The latter is mediated by Fenton reaction and prevents H2O2 accumulation. The hydroxyl radical, which is produced in the Fenton reaction, is buffered by extracellular proteins, and could not affect intracellular targets like H2O2. These findings show that anticancer effects of ascorbate have been significantly overestimated in previous in vitro studies, and that common cell culture media might be unsuitable for redox research.
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