ArticleCancer research2017
RelB Expression Determines the Differential Effects of Ascorbic Acid in Normal and Cancer Cells.
Article in Cancer research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
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Who cites it
25 citing papers in PubMed, 50 citations in OpenAlex.
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- Roles of SIRT3 in aging and aging-related diseases.International journal of biological sciences · 2025Review
- NFKBIE is a predictive factor of survival and is correlated with immune infiltration and antigen processing and presentation in hepatocellular carcinoma.Oncology letters · 2024Article
- Development of a Single-Neurosphere Culture to Assess Radiation Toxicity and Pre-Clinical Cancer Combination Therapy Safety.Cancers · 2023Article
- Hydrogen Peroxide Promotes the Production of Radiation-Derived EVs Containing Mitochondrial Proteins.Antioxidants (Basel, Switzerland) · 2022Article
- The RelB-BLNK Axis Determines Cellular Response to a Novel Redox-Active Agent Betamethasone during Radiation Therapy in Prostate Cancer.International journal of molecular sciences · 2022Article
- Human iPSC model reveals a central role for NOX4 and oxidative stress in Duchenne cardiomyopathy.Stem cell reports · 2022Article
- The Alternative RelB NF-kB Subunit Exerts a Critical Survival Function upon Metabolic Stress in Diffuse Large B-Cell Lymphoma-Derived Cells.Biomedicines · 2022Article
- 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
- Catalase Modulates the Radio-Sensitization of Pancreatic Cancer Cells by Pharmacological Ascorbate.Antioxidants (Basel, Switzerland) · 2021Article
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- Oxidative Stress in the Tumor Microenvironment and Its Relevance to Cancer Immunotherapy.Cancers · 2021Review
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- Metabolic Rewiring in Radiation Oncology Toward Improving the Therapeutic Ratio.Frontiers in oncology · 2021Review
- The XCellular oncology (Dordrecht, Netherlands) · 2020Article
- Redox modifications of cysteine-containing proteins, cell cycle arrest and translation inhibition: Involvement in vitamin C-induced breast cancer cell death.Redox biology · 2019Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Cancer cells typically experience higher oxidative stress than normal cells, such that elevating pro-oxidant levels can trigger cancer cell death. Although pre-exposure to mild oxidative agents will sensitize cancer cells to radiation, this pre-exposure may also activate the adaptive stress defense system in normal cells. Ascorbic acid is a prototype redox modulator that when infused intravenously appears to kill cancers without injury to normal tissues; however, the mechanisms involved remain elusive. In this study, we show how ascorbic acid kills cancer cells and sensitizes prostate cancer to radiation therapy while also conferring protection upon normal prostate epithelial cells against radiation-induced injury. We found that the NF-κB transcription factor RelB is a pivotal determinant in the differential radiosensitization effects of ascorbic acid in prostate cancer cells and normal prostate epithelial cells. Mechanistically, high reactive oxygen species concentrations suppress RelB in cancer cells. RelB suppression decreases expression of the sirtuin SIRT3 and the powerful antioxidant MnSOD, which in turn increases oxidative and metabolic stresses in prostate cancer cells. In contrast, ascorbic acid enhances RelB expression in normal cells, improving antioxidant and metabolic defenses against radiation injury. In addition to showing how RelB mediates the differential effects of ascorbic acid on cancer and normal tissue radiosensitivities, our work also provides a proof of concept for the existence of redox modulators that can improve the efficacy of radiotherapy while protecting against normal tissue injury in cancer settings.
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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.