The DOI matches its Crossref record; 74 of the 74 references it cites were found in a registry or an index.
O2⋅− and H2O2-Mediated Disruption of Fe Metabolism Causes the Differential Susceptibility of NSCLC and GBM Cancer Cells to Pharmacological Ascorbate
Open accessAbstract
Pharmacological ascorbate has been proposed as a potential anti-cancer agent when combined with radiation and chemotherapy. The anti-cancer effects of ascorbate are hypothesized to involve the autoxidation of ascorbate leading to increased steady-state levels of H 2 O 2; however, the mechanism(s) for cancer cell-selective toxicity remain unknown. The current study shows that alterations in cancer cell mitochondrial oxidative metabolism resulting in increased levels of O 2⋅- and H 2 O 2 are capable of disrupting intracellular iron metabolism, thereby selectively sensitizing non-small-cell lung cancer (NSCLC) and glioblastoma (GBM) cells to ascorbate through pro-oxidant chemistry involving redox-active labile iron and H 2 O 2. In addition, preclinical studies and clinical trials demonstrate the feasibility, selective toxicity, tolerability, and potential efficacy of pharmacological ascorbate in GBM and NSCLC therapy.
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“an increased level of mitochondrial ROS in lung and glioblastoma cancer cells led to increased levels of intracellular labile iron through the upregulation of the Tf receptor (TfR), thus increasing the sensitivity of these cancer cells to ascorbate43.”
From Targeting cancer vulnerabilities with high-dose vitamin C (2019) · cites this paper as [43]
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“Numerous preclinical and clinical studies indicate that parenteral injection of pharmacological ascorbate does not interfere with chemotherapy or radiotherapy and may even act synergistically43,104,105.”
From Targeting cancer vulnerabilities with high-dose vitamin C (2019) · cites this paper as [43]
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“Numerous preclinical and clinical studies indicate that parenteral injection of pharmacological ascorbate does not interfere with chemotherapy or radiotherapy and may even act synergistically43,104,105.”
From Targeting cancer vulnerabilities with high-dose vitamin C (2019) · cites this paper as [43]
In the citing paper
“This study shows that pharmacological ascorbate selectively sensitizes non-small-cell lung cancer (NSCLC) and glioblastoma (GBM) cells by generating redox-active labile iron and H2O2 using in vitro cell lines and mouse models.”
From Targeting cancer vulnerabilities with high-dose vitamin C (2019) · cites this paper as [43]
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“In addition, it shows the potential efficacy of ascorbate therapy combined with other chemotherapies in patients with GBM and NSCLC.”
From Targeting cancer vulnerabilities with high-dose vitamin C (2019) · cites this paper as [43]
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Cites
PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENT
Lowry, O. H., Rosebrough, N., Farr, A. L., & Randall, R. (1951) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)52451-6 · Cited by 316,394
New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)
Eisenhauer, E. A., Therasse, P., Bogaerts, J., Schwartz, L. H., Sargent, D., Ford, R., Dancey, J., Arbuck, S., Gwyther, S., Mooney, M., et al. (2009) · European Journal of Cancer · doi:10.1016/j.ejca.2008.10.026 · Cited by 29,534
Radiotherapy Plus Concomitant and Adjuvant Temozolomide for Glioblastoma
Stupp, R., Mason, W. P., van den Bent, M. J., Weller, M., Fisher, B., Taphoorn, M. J. B., Belanger, K., Brandes, A. A., Marosi, C., Bogdahn, U., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa043330 · Cited by 21,807
MGMT Gene Silencing and Benefit from Temozolomide in Glioblastoma
Hegi, M. E., Diserens, A.-C., Gorlia, T., Hamou, M.-F., de Tribolet, N., Weller, M., Kros, J. M., Hainfellner, J. A., Mason, W., Mariani, L., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa043331 · Cited by 7,405
Paclitaxel–Carboplatin Alone or with Bevacizumab for Non–Small-Cell Lung Cancer
Sandler, A., Gray, R., Perry, M. C., Brahmer, J., Schiller, J. H., Dowlati, A., Lilenbaum, R., & Johnson, D. H. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa061884 · Cited by 5,761
[1] Role of free radicals and catalytic metal ions in human disease: An overview
Halliwell, B., & Gutteridge, J. M. C. (1990) · Methods in Enzymology · doi:10.1016/0076-6879(90)86093-b · Cited by 4,994
Comparison of Four Chemotherapy Regimens for Advanced Non–Small-Cell Lung Cancer
Schiller, J. H., Harrington, D., Belani, C. P., Langer, C., Sandler, A., Krook, J., Zhu, J., & Johnson, D. H. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa011954 · Cited by 4,955
DISC ELECTROPHORESIS‐I BACKGROUND AND THEORY*
Ornstein, L. (1964) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1964.tb14207.x · Cited by 4,575
COMPARISON OF FOUR CHEMOTHERAPY REGIMENS FOR ADVANCED NON-SMALL-CELL LUNG CANCER
Chiller, J. O. H. S., Arrington, D. A. H., Elani, C. H. P. B., Anger, C., Andler, A. L. S., Rook, J. A. K., Hu, J., & Ohnson, D. A. H. J. (2002) · Cited by 3,730
Production of large amounts of hydrogen peroxide by human tumor cells.
Szatrowski, T. P., & Nathan, C. (1991) · PubMed · Cited by 2,504
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- Spitz, 2001, Measurement of MnSOD and CuZnSOD activity in mammalian tissue homogenates, Curr. Protoc. Toxicol., Chapter 7
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Jomova, K., Alomar, S. Y., Alwasel, S. H., Nepovimova, E., Kuca, K., & Valko, M. (2024) · Archives of Toxicology · doi:10.1007/s00204-024-03696-4 · Cited by 1,445
The Complex Interplay between Antioxidants and ROS in Cancer
Harris, I. S., & DeNicola, G. M. (2020) · Trends in Cell Biology · doi:10.1016/j.tcb.2020.03.002 · Cited by 659
Dixon, S. J., & Stockwell, B. R. (2018) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-030518-055844 · Cited by 607
Iron homeostasis and iron-regulated ROS in cell death, senescence and human diseases
Nakamura, T., Naguro, I., & Ichijo, H. (2019) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2019.06.010 · Cited by 529
Two Faces of Vitamin C—Antioxidative and Pro-Oxidative Agent
Kaźmierczak-Barańska, J., Boguszewska, K., Adamus-Grabicka, A., & Karwowski, B. T. (2020) · Nutrients · doi:10.3390/nu12051501 · Cited by 455
Metadata
- Authors
- Schoenfeld, J. D., Sibenaller, Z. A., Mapuskar, K. A., Wagner, B. A., Cramer-Morales, K. L., Furqan, M., Sandhu, S., Carlisle, T. L., Smith, M. C., Abu Hejleh, T., Berg, D. J., Zhang, J., Keech, J., Parekh, K. R., Bhatia, S., Monga, V., Bodeker, K. L., Ahmann, L., Vollstedt, S., Brown, H., Shanahan Kauffman, E. P., Schall, M. E., Hohl, R. J., Clamon, G. H., Greenlee, J. D., Howard, M. A., Schultz, M. K., Smith, B. J., Riley, D. P., Domann, F. E., Cullen, J. J., Buettner, G. R., Buatti, J. M., Spitz, D. R., & Allen, B. G.
- Affiliations
- University of Iowa (US)
- Galera Therapeutics, Inc. (United States) (US)
- Corresponding author
- Spitz, Douglas R.
- Allen, Bryan G.
- ORCID
- Schoenfeld, Joshua D.
- Sibenaller, Zita A.
- Mapuskar, Kranti A.
- Wagner, Brett A.
- Furqan, Muhammad
- Sandhu, Sonia
- Smith, Mark C.
- Berg, Daniel J.
- Zhang, Jun
- Keech, John
- Parekh, Kalpaj R.
- Monga, Varun
- Bodeker, Kellie L.
- Vollstedt, Sandy
- Brown, Heather
- Greenlee, Jeremy D.
- Howard, Matthew A.
- Schultz, Michael K.
- Riley, Dennis P.
- Domann, Frederick E.
- Cullen, Joseph J.
- Buettner, Garry R.
- Buatti, John M.
- Spitz, Douglas R.
- Allen, Bryan G.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2017-04
- Volume
- 31
- Issue
- 4
- Pages
- 487-500.e8
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC5497844
- OpenAlex
- W2597494578
- Cited by
- 443
- References
- 74
- Citations by year
- 2026: 27 · 2025: 34 · 2024: 44 · 2023: 52 · 2022: 59 · 2021: 56 · 2020: 61 · 2019: 45 · 2018: 45 · 2017: 20
- FWCI
- 38.88
- Type
- journal article
- Language
- en
- Update notices
- erratum (2017-08-14)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Society for Radiation Oncology (JF2014-1)
- Carver Research Program of Excellence in Redox Biology
- US NIH (R01-CA182804, R01-CA184051, R01-CA169046, U01-CA166800)
- IBM
- CCSG (P30-CA086862)
- University of Iowa Medical Scientist Training Program (T32-GM007337, T32-CA078586)
- Galera Therapeutics
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
- Keywords
- pharmacological ascorbate, reactive oxygen species, superoxide, hydrogen peroxide, mitochondrial oxidative metabolism, non-small cell lung cancer, glioblastoma
- MeSH terms
- Animals, Antineoplastic Combined Chemotherapy Protocols, Ascorbic Acid, Brain Neoplasms, Carcinoma, Non-Small-Cell Lung, Female, Glioblastoma, Humans, Hydrogen Peroxide, Iron, Lung Neoplasms, Male, Mice, Nude, Oxygen, Radiation-Sensitizing Agents, Xenograft Model Antitumor Assays, Cell Line, Tumor, Chemoradiotherapy
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