Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
April-2026 Volume 55 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
April-2026 Volume 55 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML

  • Supplementary Files
    • Supplementary_Data.pdf
Article Open Access

Role of iron and TfR1 in the application of high‑dose ascorbate against pancreatic cancer

  • Authors:
    • Alban Piotrowsky
    • Christian Leischner
    • Hendrik Schmieder
    • Katja Detert
    • Kathrin Schneider
    • Johanna Schulte
    • Sabrina Hammerschmidt
    • Luigi Marongiu
    • Olga Renner
    • Markus Burkard
    • Sascha Venturelli
  • View Affiliations / Copyright

    Affiliations: Department of Nutritional Biochemistry, Institute of Nutritional Sciences, University of Hohenheim, D‑70599 Stuttgart, Germany, Bavarian Center for Cancer Research (BZKF), D‑86156 Augsburg, Germany, Hochschule Niederrhein, University of Applied Sciences, Faculty of Food and Nutrition Sciences, D‑41065 Moenchengladbach, Germany
    Copyright: © Piotrowsky et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 78
    |
    Published online on: February 24, 2026
       https://doi.org/10.3892/or.2026.9083
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:


Abstract

Pancreatic cancer remains one of the deadliest tumor diseases with an urgent need for new therapy options. At the same time, the use of high‑dose vitamin C in cancer treatment has been investigated for decades. Despite promising in vitro and in vivo data and initial clinical studies, there is a need for optimization with regard to an ideal treatment regimen and suitable patient population for the use of high‑dose vitamin C. The aim of the present study was to evaluate for the first time the combination of high‑dose vitamin C with the administration of iron in three human pancreatic cancer cell lines and to determine the exact cell death mechanism. While the investigated cell lines showed a high susceptibility to ascorbate treatment, the combination treatment with FeCl3 generally led to a reduction in the ascorbate effect and in the formation of reactive oxygen species. The ascorbate‑induced cell death showed no signs of apoptosis but clear ferroptotic properties. Furthermore, treatment of the tumor cells with FeCl3 was accompanied by reduced expression of TfR1, preventing an increase in the intracellular labile iron pool. The present study provided valuable information on the mechanism of action of high‑dose vitamin C in pancreatic cancer, whereby a combination treatment with ferric iron in the context of tumor therapy is not recommended based on these data.
View Figures

Figure 1

Influence of high-dose ascorbate
alone or in combination with ferric iron on the viability of human
pancreatic cancer cell lines. The cell lines BxPC-3, MIA PaCa-2 and
PANC-1 were either treated for 24 h with the indicated ascorbate
concentrations alone (A), in the form of coincubation
simultaneously with ascorbate and 100 µM FC (B), or incubated with
100 µM FC for 24 h as a preincubation before ascorbate treatment
(C). Triton™ X-100 at 0.1% (v/v) served as positive control. Cell
viability was measured after treatment by MUH assay. The results
are presented as a percentage of fluorescence intensity relative to
the untreated control. Three independent experiments were performed
in duplicates. Error bars represent the mean ± SD, statistical
analysis with one-way ANOVA and subsequent Dunnett's multiple
comparisons test, confidence interval 95%. *P≤0.05, **P≤0.01, and
***P≤0.001. Asc, ascorbate; FC, ferric chloride; MUH,
4-methylumbelliferyl heptanoate.

Figure 2

Investigation of the effect of
high-dose ascorbate treatment on different apoptosis markers in
human pancreatic cancer cell lines. A possible induction of
apoptosis in the human pancreatic cancer cell lines BxPC-3, MIA
PaCa-2, and PANC-1 was investigated by testing caspase-3 cleavage
by flow cytometry (A) and western blotting (B). Cells were treated
for 6 h with the indicated ascorbate concentrations. 20 µM STS
served as positive control. Three independent experiments were
performed. Morphological nuclear changes were detected by
fluorescence microscopy. The white scale bars represent 25 µm. (C).
Cells were treated with the indicated ascorbate concentrations for
6 h and then fixed. 10 µM STS served as positive control. The
nuclei were stained with DAPI (blue), the cytoskeleton with
phalloidin (red). A representative experiment is shown. Cell cycle
analysis was performed by flow cytometry (D). Cells were treated
with the indicated ascorbate concentrations for 24 h, fixed,
stained with PI, and subsequently detected. Treatment with 1 µM STS
for 20 h served as positive control. Three independent experiments
were performed. Error bars represent the mean ± SD, statistical
analysis with one-way ANOVA and subsequent Dunnett's multiple
comparisons test, confidence interval 95%. *P≤0.05 and ***P≤0.001.
Asc, ascorbate; DAPI, diamidino-2-phenylindole; PI, propidium
iodide; STS, staurosporine.

Figure 3

Investigation of the effect of
high-dose ascorbate treatment on different ferroptosis markers in
human pancreatic cancer cell lines. The human pancreatic cancer
cell lines BxPC-3, MIA PaCa-2, and PANC-1 were treated with or
without the ferroptosis inhibitor DFO for 24 h, after which cell
viability was measured using the MUH assay (A). Triton™ X-100 at
0.1% (v/v) served as positive control. The results are presented as
a percentage of the fluorescence intensity of the untreated
control. Three independent experiments were performed in
duplicates. As further signs of ferroptosis, protein expression of
TfR1, GPX4, and LC3B-II was detected by western blotting (B) and
quantified densitometrically (C). Cells were treated with the
indicated ascorbate concentrations for 6 h, after which a western
blot was performed. 5 µM RSL3 or 60 µM CQ together with 500 nM RAPA
were used as positive controls. Signal intensity was analyzed
densitometrically and normalized to GAPDH. One representative
experiment out of two is shown. Error bars represent the mean ± SD,
statistical analysis with one-way ANOVA and subsequent Dunnett's
multiple comparisons test, confidence interval 95%. **P≤0.01 and
***P≤0.001. Asc, ascorbate; CQ, chloroquine; DFO, deferoxamine
mesylate; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; GPX4,
glutathione peroxidase 4; MUH, 4-methylumbelliferyl heptanoate;
RAPA, rapamycin; RSL3, RAS-selective lethal 3; TfR1, transferrin
receptor 1.

Figure 4

The influence of iron and TfR1 on the
ascorbate effect in human pancreatic cancer cell lines. To
investigate the effect of iron on ascorbate action, the three human
pancreatic cancer cell lines BxPC-3, MIA PaCa-2, and PANC-1 were
either incubated simultaneously for 6 h with ascorbate at different
concentrations and 100 µM ferric chloride (FC) (A) or treated with
ascorbate after 24 h preincubation with ferric chloride (B). The
intracellular ROS levels were determined after treatment by flow
cytometry using the DCFH-DA assay. The percentage of DCF-positive
cells is shown as a measure of intracellular ROS accumulation.
Statistically significant differences between the combination
treatment with iron and ascorbate treatment alone are marked by
asterisks. Three independent experiments were performed. The
intracellular LIP after 24-h incubation with ferric chloride was
determined by flow cytometry using the calcein AM assay (C). The
relative labile iron pool is shown in relation to the untreated
control. Three independent experiments were performed. The basal
protein expression of TfR1 in the pancreatic cancer cell lines and
the non-malignant pancreatic ductal epithelial cell line HPDE6c7
was determined by western blotting, as well as the influence of
ferric chloride on TfR1 expression in the three pancreatic cancer
cell lines (D). The western blot results were also analyzed
densitometrically. A representative experiment is shown for basal
expression. For TfR1 expression after iron treatment, two
independent experiments were performed, a representative western
blot is shown. The influence of the 24-h ferric chloride treatment
as well as ascorbate treatment was additionally determined at the
mRNA level by qPCR (E). Error bars represent the mean ± SD,
statistical analysis with one-way ANOVA and subsequent Dunnett's
multiple comparisons test, confidence interval 95%. *P≤0.05,
**P≤0.01, and ***P≤0.001. Asc, ascorbate; DCFH-DA,
dichlorodihydrofluorescein diacetate; DCF, dichlorofluorescein; FC,
ferric chloride; LIP, labile iron pool; ROS, reactive oxygen
species; TfR1, transferrin receptor 1.

Figure 5

Hypothesized mechanism of
ascorbate-induced cell death in pancreatic cancer cells. Asc is
being oxidized outside the cell to DHA by ferric iron. This results
in the accumulation of ferrous iron, which reacts with molecular
oxygen and then with the superoxide radical anion to form hydrogen
peroxide. Hydrogen peroxide enters the cancer cell via AQPs. Ferric
iron itself enters the cell via TfR1, a process that is inhibited
by intracellular iron accumulation and increased LIP. Once inside
the cancer cell, hydrogen peroxide reacts with ferrous iron to form
the hydroxyl radical, causing oxidative stress through ROS
accumulation. This inhibits the antioxidant activity of GPX4,
promotes autophagy, and finally induces ferroptotic cell death.
Ferroptosis is inhibited by DFO. Asc, ascorbate; AQP, aquaporin;
DFO, deferoxamine mesylate; DHA dehydroascorbic acid; GPX4,
glutathione peroxidase 4; LIP, labile iron pool; PUFA,
polyunsaturated fatty acids; ROS, reactive oxygen species; TfR1,
transferrin receptor 1.
View References

1 

Siegel RL, Giaquinto AN and Jemal A: Cancer statistics, 2024. CA Cancer J Clin. 74:12–49. 2024.PubMed/NCBI

2 

Rahib L, Wehner MR, Matrisian LM and Nead KT: Estimated projection of US cancer incidence and death to 2040. JAMA Netw Open. 4:e2147082021. View Article : Google Scholar : PubMed/NCBI

3 

American Cancer Society, . Cancer facts & figures. 2024.Available from:. https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/2024-cancer-facts-figures.html

4 

National Cancer Institute, . Cancer Stat Facts: Common Cancer Sites. 2025.Available from:. https://seer.cancer.gov/statfacts/html/common.html

5 

Cameron E and Pauling L: Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer. Proc Natl Acad Sci USA. 73:3685–3689. 1976. View Article : Google Scholar : PubMed/NCBI

6 

Cameron E and Pauling L: Supplemental ascorbate in the supportive treatment of cancer: Reevaluation of prolongation of survival times in terminal human cancer. Proc Natl Acad Sci USA. 75:4538–4542. 1978. View Article : Google Scholar : PubMed/NCBI

7 

Ou J, Zhu X, Lu Y, Zhao C, Zhang H, Wang X, Gui X, Wang J, Zhang X, Zhang T and Pang CLK: The safety and pharmacokinetics of high dose intravenous ascorbic acid synergy with modulated electrohyperthermia in Chinese patients with stage III–IV non-small cell lung cancer. Eur J Pharm Sci. 109:412–418. 2017. View Article : Google Scholar

8 

Padayatty SJ, Sun H, Wang Y, Riordan HD, Hewitt SM, Katz A, Wesley RA and Levine M: Vitamin C pharmacokinetics: Implications for oral and intravenous use. Ann Intern Med. 140:533–537. 2004. View Article : Google Scholar : PubMed/NCBI

9 

Böttger F, Vallés-Martí A, Cahn L and Jimenez CR: High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer. J Exp Clin Cancer Res. 40:3432021. View Article : Google Scholar

10 

Kim JH, Hwang S, Lee JH, Im SS and Son J: Vitamin C suppresses pancreatic carcinogenesis through the inhibition of both glucose metabolism and wnt signaling. Int J Mol Sci. 23:122492022. View Article : Google Scholar

11 

O'Leary BR, Alexander MS, Du J, Moose DL, Henry MD and Cullen JJ: Pharmacological ascorbate inhibits pancreatic cancer metastases via a peroxide-mediated mechanism. Sci Rep. 10:176492020. View Article : Google Scholar

12 

Bodeker KL, Smith BJ, Berg DJ, Chandrasekharan C, Sharif S, Fei N, Vollstedt S, Brown H, Chandler M, Lorack A, et al: A randomized trial of pharmacological ascorbate, gemcitabine, and nab-paclitaxel for metastatic pancreatic cancer. Redox Biol. 77:1033752024. View Article : Google Scholar

13 

Alexander MS, Wilkes JG, Schroeder SR, Buettner GR, Wagner BA, Du J, Gibson-Corley K, O'Leary BR, Spitz DR, Buatti JM, et al: Pharmacologic ascorbate reduces radiation-induced normal tissue toxicity and enhances tumor radiosensitization in pancreatic cancer. Cancer Res. 78:6838–6851. 2018. View Article : Google Scholar : PubMed/NCBI

14 

Chen P, Reed G, Jiang J, Wang Y, Sunega J, Dong R, Ma Y, Esparham A, Ferrell R, Levine M, et al: Pharmacokinetic evaluation of intravenous Vitamin C: A classic pharmacokinetic study. Clin Pharmacokinet. 61:1237–1249. 2022. View Article : Google Scholar

15 

Polireddy K, Dong R, Reed G, Yu J, Chen P, Williamson S, Violet PC, Pessetto Z, Godwin AK, Fan F, et al: High dose parenteral ascorbate inhibited pancreatic cancer growth and metastasis: Mechanisms and a phase I/IIa study. Sci Rep. 7:171882017. View Article : Google Scholar : PubMed/NCBI

16 

Welsh JL, Wagner BA, van't Erve TJ, Zehr PS, Berg DJ, Halfdanarson TR, Yee NS, Bodeker KL, Du J, Roberts LJ II, et al: Pharmacological ascorbate with gemcitabine for the control of metastatic and node-positive pancreatic cancer (PACMAN): Results from a phase I clinical trial. Cancer Chemother Pharmacol. 71:765–775. 2013. View Article : Google Scholar

17 

Fan D, Liu X, Shen Z, Wu P, Zhong L and Lin F: Cell signaling pathways based on vitamin C and their application in cancer therapy. Biomed Pharmacother. 162:1146952023. View Article : Google Scholar : PubMed/NCBI

18 

Piotrowsky A, Burkard M, Schmieder H, Venturelli S, Renner O and Marongiu L: The therapeutic potential of vitamins A, C, and D in pancreatic cancer. Heliyon. 11:e415982025. View Article : Google Scholar : PubMed/NCBI

19 

Du J, Cullen JJ and Buettner GR: Ascorbic acid: Chemistry, biology and the treatment of cancer. Biochim Biophys Acta. 1826:443–457. 2012.

20 

González-Montero J, Chichiarelli S, Eufemi M, Altieri F, Saso L and Rodrigo R: Ascorbate as a bioactive compound in cancer therapy: The old classic strikes back. Molecules. 27:38182022. View Article : Google Scholar

21 

Schoenfeld JD, Alexander MS, Waldron TJ, Sibenaller ZA, Spitz DR, Buettner GR, Allen BG and Cullen JJ: Pharmacological ascorbate as a means of sensitizing cancer cells to Radio-chemotherapy while protecting normal tissue. Semin Radiat Oncol. 29:25–32. 2019. View Article : Google Scholar

22 

Leischner C, Marongiu L, Piotrowsky A, Niessner H, Venturelli S, Burkard M and Renner O: Relevant membrane transport proteins as possible gatekeepers for effective pharmacological ascorbate treatment in cancer. Antioxidants (Basel). 12:9162023. View Article : Google Scholar : PubMed/NCBI

23 

Piotrowsky A, Burkard M, Hammerschmidt K, Ruple HK, Nonnenmacher P, Schumacher M, Leischner C, Berchtold S, Marongiu L, Kufer TA, et al: Analysis of High-dose ascorbate-induced cytotoxicity in human glioblastoma cells and the role of dehydroascorbic acid and iron. Antioxidants (Basel). 13:10952024. View Article : Google Scholar : PubMed/NCBI

24 

Zhou L, Zhang L, Wang S, Zhao B, Lv H and Shang P: Labile iron affects pharmacological ascorbate-induced toxicity in osteosarcoma cell lines. Free Radic Res. 54:385–396. 2020. View Article : Google Scholar : PubMed/NCBI

25 

Schoenfeld JD, Sibenaller ZA, Mapuskar KA, Wagner BA, Cramer-Morales KL, Furqan M, Sandhu S, Carlisle TL, Smith MC, Abu Hejleh T, et al: O2·- and H2O2-mediated disruption of fe metabolism causes the differential susceptibility of NSCLC and GBM cancer cells to pharmacological ascorbate. Cancer Cell. 31:487–500.e8. 2017. View Article : Google Scholar

26 

Du J, Wagner BA, Buettner GR and Cullen JJ: Role of labile iron in the toxicity of pharmacological ascorbate. Free Radic Biol Med. 84:289–295. 2015. View Article : Google Scholar : PubMed/NCBI

27 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

28 

Burkard M, Niessner H, Leischner C, Piotrowsky A, Renner O, Marongiu L, Lauer UM, Busch C, Sinnberg T and Venturelli S: High-dose ascorbate in combination with Anti-PD1 checkpoint inhibition as treatment option for malignant melanoma. Cells. 12:2542023. View Article : Google Scholar : PubMed/NCBI

29 

Szarka A, Kapuy O, Lőrincz T and Bánhegyi G: Vitamin C and cell death. Antioxid Redox Signal. 34:831–844. 2021. View Article : Google Scholar

30 

Chen X, Comish PB, Tang D and Kang R: Characteristics and biomarkers of ferroptosis. Front Cell Dev Biol. 9:6371622021. View Article : Google Scholar

31 

Brandt KE, Falls KC, Schoenfeld JD, Rodman SN, Gu Z, Zhan F, Cullen JJ, Wagner BA, Buettner GR, Allen BG, et al: Augmentation of intracellular iron using iron sucrose enhances the toxicity of pharmacological ascorbate in colon cancer cells. Redox Biol. 14:82–87. 2018. View Article : Google Scholar

32 

Deme S, Ramezani I, Coulter J, Paller C and Bressler J: Effects of hypoxia and iron on ascorbic acid-mediated cytotoxicity in prostate cancer cell lines. Toxicol Appl Pharmacol. 497:1172592025. View Article : Google Scholar

33 

Wang F, He MM, Xiao J, Zhang YQ, Yuan XL, Fang WJ, Zhang Y, Wang W, Hu XH, Ma ZG, et al: A randomized, open-label, multicenter, phase 3 study of high-dose Vitamin C Plus FOLFOX ± bevacizumab versus FOLFOX ± bevacizumab in unresectable untreated metastatic colorectal cancer (VITALITY study). Clin Cancer Res. 28:4232–4239. 2022. View Article : Google Scholar : PubMed/NCBI

34 

Mohammad RM, Muqbil I, Lowe L, Yedjou C, Hsu HY, Lin LT, Siegelin MD, Fimognari C, Kumar NB, Dou QP, et al: Broad targeting of resistance to apoptosis in cancer. Semin Cancer Biol. 35 (Suppl(0)):S78–S103. 2015. View Article : Google Scholar

35 

Renner O, Burkard M, Michels H, Vollbracht C, Sinnberg T and Venturelli S: Parenteral high-dose ascorbate-A possible approach for the treatment of glioblastoma (Review). Int J Oncol. 58:352021. View Article : Google Scholar

36 

Wu K, Liu L, Wu Z, Huang Q, Zhou L, Xie R and Wang M: Ascorbic acid induces ferroptosis via STAT3/GPX4 signaling in oropharyngeal cancer. Free Radic Res. 58:117–129. 2024. View Article : Google Scholar : PubMed/NCBI

37 

Wang X, Xu S, Zhang L, Cheng X, Yu H, Bao J and Lu R: Vitamin C induces ferroptosis in anaplastic thyroid cancer cells by ferritinophagy activation. Biochem Biophys Res Commun. 551:46–53. 2021. View Article : Google Scholar : PubMed/NCBI

38 

Liu Y, Huang P, Li Z, Xu C, Wang H, Jia B, Gong A and Xu M: Vitamin C sensitizes pancreatic cancer cells to erastin-induced ferroptosis by activating the AMPK/Nrf2/HMOX1 pathway. Oxid Med Cell Longev. 2022:53612412022. View Article : Google Scholar : PubMed/NCBI

39 

Zhang C, Liu X, Jin S, Chen Y and Guo R: Ferroptosis in cancer therapy: A novel approach to reversing drug resistance. Mol Cancer. 21:472022. View Article : Google Scholar : PubMed/NCBI

40 

Schaefer B, Meindl E, Wagner S, Tilg H and Zoller H: Intravenous iron supplementation therapy. Mol Aspects Med. 75:1008622020. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Piotrowsky A, Leischner C, Schmieder H, Detert K, Schneider K, Schulte J, Hammerschmidt S, Marongiu L, Renner O, Burkard M, Burkard M, et al: Role of iron and TfR1 in the application of high‑dose ascorbate against pancreatic cancer. Oncol Rep 55: 78, 2026.
APA
Piotrowsky, A., Leischner, C., Schmieder, H., Detert, K., Schneider, K., Schulte, J. ... Venturelli, S. (2026). Role of iron and TfR1 in the application of high‑dose ascorbate against pancreatic cancer. Oncology Reports, 55, 78. https://doi.org/10.3892/or.2026.9083
MLA
Piotrowsky, A., Leischner, C., Schmieder, H., Detert, K., Schneider, K., Schulte, J., Hammerschmidt, S., Marongiu, L., Renner, O., Burkard, M., Venturelli, S."Role of iron and TfR1 in the application of high‑dose ascorbate against pancreatic cancer". Oncology Reports 55.4 (2026): 78.
Chicago
Piotrowsky, A., Leischner, C., Schmieder, H., Detert, K., Schneider, K., Schulte, J., Hammerschmidt, S., Marongiu, L., Renner, O., Burkard, M., Venturelli, S."Role of iron and TfR1 in the application of high‑dose ascorbate against pancreatic cancer". Oncology Reports 55, no. 4 (2026): 78. https://doi.org/10.3892/or.2026.9083
Copy and paste a formatted citation
x
Spandidos Publications style
Piotrowsky A, Leischner C, Schmieder H, Detert K, Schneider K, Schulte J, Hammerschmidt S, Marongiu L, Renner O, Burkard M, Burkard M, et al: Role of iron and TfR1 in the application of high‑dose ascorbate against pancreatic cancer. Oncol Rep 55: 78, 2026.
APA
Piotrowsky, A., Leischner, C., Schmieder, H., Detert, K., Schneider, K., Schulte, J. ... Venturelli, S. (2026). Role of iron and TfR1 in the application of high‑dose ascorbate against pancreatic cancer. Oncology Reports, 55, 78. https://doi.org/10.3892/or.2026.9083
MLA
Piotrowsky, A., Leischner, C., Schmieder, H., Detert, K., Schneider, K., Schulte, J., Hammerschmidt, S., Marongiu, L., Renner, O., Burkard, M., Venturelli, S."Role of iron and TfR1 in the application of high‑dose ascorbate against pancreatic cancer". Oncology Reports 55.4 (2026): 78.
Chicago
Piotrowsky, A., Leischner, C., Schmieder, H., Detert, K., Schneider, K., Schulte, J., Hammerschmidt, S., Marongiu, L., Renner, O., Burkard, M., Venturelli, S."Role of iron and TfR1 in the application of high‑dose ascorbate against pancreatic cancer". Oncology Reports 55, no. 4 (2026): 78. https://doi.org/10.3892/or.2026.9083
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team