ArticleCancer research2013
Manganoporphyrins increase ascorbate-induced cytotoxicity by enhancing H2O2 generation.
Article in Cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
47 citing papers in PubMed, 78 citations in OpenAlex.
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- 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
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- Vitamin C Supplementation in the Treatment of Autoimmune and Onco-Hematological Diseases: From Prophylaxis to Adjuvant Therapy.International journal of molecular sciences · 2024Review
- Pharmacologic Ascorbate Radiosensitizes Pancreatic Cancer but Radioprotects Normal Tissue: The Role of Oxidative Stress-Induced Lipid Peroxidation.Antioxidants (Basel, Switzerland) · 2024Article
- Hydrogen Peroxide Mediates Pharmacological Ascorbate Induced Radio-Sensitization of Pancreatic Cancer Cells by Enhancing G2-accumulation and Reducing Cyclin B1 Protein Levels.Radiation research · 2023Article
- High-Dose Vitamin C for Cancer Therapy.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Alternative medicine: therapeutic effects on gastric original signet ring carcinoma via ascorbate and combination with sodium alpha lipoate.BMC complementary medicine and therapies · 2022Article
- Ascorbate-dependent and ascorbate-independent Mn porphyrin cytotoxicity: anticancer activity of Mn porphyrin-based SOD mimics through ascorbate-dependent and -independent routes.Redox report : communications in free radical research · 2021Article
- Targeting oxidative stress in disease: promise and limitations of antioxidant therapy.Nature reviews. Drug discovery · 2021Review
- Impact of EcSOD Perturbations in Cancer Progression.Antioxidants (Basel, Switzerland) · 2021Review
- Catalase Modulates the Radio-Sensitization of Pancreatic Cancer Cells by Pharmacological Ascorbate.Antioxidants (Basel, Switzerland) · 2021Article
- The latency of peroxisomal catalase in terms of effectiveness factor for pancreatic and glioblastoma cancer cell lines in the presence of high concentrations of HFree radical biology & medicine · 2020Article
- Dual Oxidase-Induced Sustained Generation of Hydrogen Peroxide Contributes to Pharmacologic Ascorbate-Induced Cytotoxicity.Cancer research · 2020Article
- Pharmacologic Ascorbate Primes Pancreatic Cancer Cells for Death by Rewiring Cellular Energetics and Inducing DNA Damage.Molecular cancer research : MCR · 2019Article
- Targeting cancer vulnerabilities with high-dose vitamin C.Nature reviews. Cancer · 2019Review
- Pro- and Antioxidant Effects of Vitamin C in Cancer in correspondence to Its Dietary and Pharmacological Concentrations.Oxidative medicine and cellular longevity · 2019Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Renewed interest in using pharmacological ascorbate (AscH-) to treat cancer has prompted interest in leveraging its cytotoxic mechanism of action. A central feature of AscH- action in cancer cells is its ability to act as an electron donor to O2 for generating H2O2. We hypothesized that catalytic manganoporphyrins (MnP) would increase AscH- oxidation rates, thereby increasing H2O2 fluxes and cytotoxicity. Three different MnPs were tested (MnTBAP, MnT2EPyP, and MnT4MPyP), exhibiting a range of physicochemical and thermodynamic properties. Of the MnPs tested, MnT4MPyP exerted the greatest effect on increasing the rate of AscH- oxidation as determined by the concentration of ascorbate radical [Asc•-] and the rate of oxygen consumption. At concentrations that had minimal effects alone, combining MnPs and AscH- synergized to decrease clonogenic survival in human pancreatic cancer cells. This cytotoxic effect was reversed by catalase, but not superoxide dismutase, consistent with a mechanism mediated by H2O2. MnPs increased steady-state concentrations of Asc•- upon ex vivo addition to whole blood obtained either from mice infused with AscH- or patients treated with pharmacologic AscH-. Finally, tumor growth in vivo was inhibited more effectively by combining MnT4MPyP with AscH-. We concluded that MnPs increase the rate of oxidation of AscH- to leverage H2O2 flux and ascorbate-induced cytotoxicity.
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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.