ArticleFree radical biology & medicine2014
Mn porphyrin in combination with ascorbate acts as a pro-oxidant and mediates caspase-independent cancer cell death.
Article in Free radical biology & medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed.
- An injectable thermosensitive PLGA-PEG-PLGA hydrogel integrated with coordination-driven self-assembled MTX-Mn nanoparticles for enhanced melanoma therapyRSC advances · 2026Article
- Radiomitigators: Breakthroughs in Post-Radiation Recovery.Antioxidants (Basel, Switzerland) · 2026Review
- An Antioxidant Cocktail ofAntioxidants (Basel, Switzerland) · 2026Article
- Article
- Mn(III) Porphyrin MnTE-2-PyPACS infectious diseases · 2025Article
- Superoxide Dismutase Mimetic Avasopasem Manganese Enhances Radiation Therapy Effectiveness in Soft Tissue Sarcomas and Accelerates Wound Healing.Antioxidants (Basel, Switzerland) · 2024Article
- The NF-κB Transcriptional Network Is a High-Dose Vitamin C-Targetable Vulnerability in Breast Cancer.Biomedicines · 2023Review
- The bovine dialyzable leukocyte extract, immunepotent CRP, synergically enhances cyclophosphamide-induced breast cancer cell death, through a caspase-independent mechanism.EXCLI journal · 2023Article
- Assessing the In Vitro Activity of Selected Porphyrins in Human Colorectal Cancer Cells.Molecules (Basel, Switzerland) · 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
- Optimization, Characterization and Pharmacokinetic Study of Meso-Tetraphenylporphyrin Metal Complex-Loaded PLGA Nanoparticles.International journal of molecular sciences · 2021Article
- MnTnHex-2-PyPAntioxidants (Basel, Switzerland) · 2021Article
- The Role of RBC Oxidative Stress in Sickle Cell Disease: From the Molecular Basis to Pathologic Implications.Antioxidants (Basel, Switzerland) · 2021Review
- Two Distinct Faces of Vitamin C: AA vs. DHA.Antioxidants (Basel, Switzerland) · 2021Review
- HOxidative medicine and cellular longevity · 2021Review
- Mn porphyrins as a novel treatment targeting sickle cell NOXs to reverse and prevent acute vaso-occlusion in vivo.Blood advances · 2020Article
- Manganese porphyrin, MnTE-2-PyP, treatment protects the prostate from radiation-induced fibrosis (RIF) by activating the NRF2 signaling pathway and enhancing SOD2 and sirtuin activity.Free radical biology & medicine · 2020Article
- Effects of Manganese Porphyrins on Cellular Sulfur Metabolism.Molecules (Basel, Switzerland) · 2020Article
- Hydrogen peroxide as a hydride donor and reductant under biologically relevant conditions.Chemical science · 2019Article
- Utilizing Superoxide Dismutase Mimetics to Enhance Radiation Therapy Response While Protecting Normal Tissues.Seminars in radiation oncology · 2019Review
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4 authors.
Funding
Abstract
Resistance to therapy-mediated apoptosis in inflammatory breast cancer, an aggressive and distinct subtype of breast cancer, was recently attributed to increased superoxide dismutase (SOD) expression, glutathione (GSH) content, and decreased accumulation of reactive species. In this study, we demonstrate the unique ability of two Mn(III) N-substituted pyridylporphyrin (MnP)-based SOD mimics (MnTE-2-PyP(5+) and MnTnBuOE-2-PyP(5+)) to catalyze oxidation of ascorbate, leading to the production of excessive levels of peroxide, and in turn cell death. The accumulation of peroxide, as a consequence of MnP+ascorbate treatment, was fully reversed by the administration of exogenous catalase, showing that hydrogen peroxide is essential for cell death. Cell death as a consequence of the action of MnP+ascorbate corresponded to decreases in GSH levels, prosurvival signaling (p-NF-κB, p-ERK1/2), and in expression of X-linked inhibitor of apoptosis protein, the most potent caspase inhibitor. Although markers of classical apoptosis were observed, including PARP cleavage and annexin V staining, administration of a pan-caspase inhibitor, Q-VD-OPh, did not reverse the observed cytotoxicity. MnP+ascorbate-treated cells showed nuclear translocation of apoptosis-inducing factor, suggesting the possibility of a mechanism of caspase-independent cell death. Pharmacological ascorbate has already shown promise in recently completed phase I clinical trials, in which its oxidation and subsequent peroxide formation was catalyzed by endogenous metalloproteins. The catalysis of ascorbate oxidation by an optimized metal-based catalyst (such as MnP) carries a large therapeutic potential as an anticancer agent by itself or in combination with other modalities such as radio- and chemotherapy.
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