|
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
|