ArticleFree radical biology & medicine2015
Manganoporphyrins and ascorbate enhance gemcitabine cytotoxicity in pancreatic cancer.
Article in Free radical biology & medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Effect of vitamins C and E on cancer survival; a systematic review.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2022Pooled it
- Trace Elements in the Pancreas: From Physiological Homeostasis to the Pathogenesis of Diabetes, Pancreatitis, and Cancer-A Review.Life (Basel, Switzerland) · 2026Review
- Review
- Trace elements in pancreatic cancer.Cancer medicine · 2024Review
- Pharmacologic Ascorbate Radiosensitizes Pancreatic Cancer but Radioprotects Normal Tissue: The Role of Oxidative Stress-Induced Lipid Peroxidation.Antioxidants (Basel, Switzerland) · 2024Article
- Auranofin and Pharmacologic Ascorbate as Radiomodulators in the Treatment of Pancreatic Cancer.Antioxidants (Basel, Switzerland) · 2022Review
- A Redox-active Mn Porphyrin, MnTnBuOE-2-PyPOxidative medicine and cellular longevity · 2022Article
- Ascorbic acid induced TET2 enzyme activation enhances cancer immunotherapy efficacy in renal cell carcinoma.International journal of biological sciences · 2022Article
- Vitamin C Sensitizes Pancreatic Cancer Cells to Erastin-Induced Ferroptosis by Activating the AMPK/Nrf2/HMOX1 Pathway.Oxidative medicine and cellular longevity · 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
- Pharmacological ascorbate inhibits pancreatic cancer metastases via a peroxide-mediated mechanism.Scientific reports · 2020Article
- Pharmacologic Ascorbate Primes Pancreatic Cancer Cells for Death by Rewiring Cellular Energetics and Inducing DNA Damage.Molecular cancer research : MCR · 2019Article
- Enhanced Pharmacological Ascorbate Oxidation Radiosensitizes Pancreatic Cancer.Radiation research · 2019Article
- Calculated cell-specific intracellular hydrogen peroxide concentration: Relevance in cancer cell susceptibility during ascorbate therapy.Free radical biology & medicine · 2018Article
- Pharmacological Ascorbate as an Adjuvant for Enhancing Radiation-Chemotherapy Responses in Gastric Adenocarcinoma.Radiation research · 2018Article
- The Addition of Manganese Porphyrins during Radiation Inhibits Prostate Cancer Growth and Simultaneously Protects Normal Prostate Tissue from Radiation Damage.Antioxidants (Basel, Switzerland) · 2018Article
- Superoxide Dismutase Mimetic GC4419 Enhances the Oxidation of Pharmacological Ascorbate and Its Anticancer Effects in an H₂O₂-Dependent Manner.Antioxidants (Basel, Switzerland) · 2018Article
- Potential Mechanisms of Action for Vitamin C in Cancer: Reviewing the Evidence.Frontiers in physiology · 2018Review
- Pharmacologic ascorbate induces neuroblastoma cell death by hydrogen peroxide mediated DNA damage and reduction in cancer cell glycolysis.Free radical biology & medicine · 2017Article
- Superoxide Dismutases in Pancreatic Cancer.Antioxidants (Basel, Switzerland) · 2017Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Pharmacological ascorbate (AscH(-)) selectively induces cytotoxicity in pancreatic cancer cells vs normal cells via the generation of extracellular hydrogen peroxide (H2O2), producing double-stranded DNA breaks and ultimately cell death. Catalytic manganoporphyrins (MnPs) can enhance ascorbate-induced cytotoxicity by increasing the rate of AscH(-) oxidation and therefore the rate of generation of H2O2. We hypothesized that combining MnPs and AscH(-) with the chemotherapeutic agent gemcitabine would further enhance pancreatic cancer cell cytotoxicity without increasing toxicity in normal pancreatic cells or other organs. Redox-active MnPs were combined with AscH(-) and administered with or without gemcitabine to human pancreatic cancer cell lines, as well as immortalized normal pancreatic ductal epithelial cells. The MnPs MnT2EPyP (Mn(III)meso-tetrakis(N-ethylpyridinium-2-yl) porphyrin pentachloride) and MnT4MPyP (Mn(III)tetrakis(N-methylpyridinium-4-yl) porphyrin pentachloride) were investigated. Clonogenic survival was significantly decreased in all pancreatic cancer cell lines studied when treated with MnP + AscH(-) + gemcitabine, whereas nontumorigenic cells were resistant. The concentration of ascorbate radical (Asc(•-), an indicator of oxidative flux) was significantly increased in treatment groups containing MnP and AscH(-). Furthermore, MnP + AscH(-) increased double-stranded DNA breaks in gemcitabine-treated cells. These results were abrogated by extracellular catalase, further supporting the role of the flux of H2O2. In vivo growth was inhibited and survival increased in mice treated with MnT2EPyP, AscH(-), and gemcitabine without a concomitant increase in systemic oxidative stress. These data suggest a promising role for the use of MnPs in combination with pharmacologic AscH(-) and chemotherapeutics in pancreatic cancer.
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