Vitamin C in stem cell reprogramming and cancer
Open accessAbstract
Vitamin C is an essential dietary requirement for humans. In addition to its known role as an antioxidant, vitamin C is a cofactor for Fe 2+- and α-ketoglutarate-dependent dioxygenases (Fe 2+/α-KGDDs) which comprise a large number of diverse enzymes, including collagen prolyl hydroxylases and epigenetic regulators of histone and DNA methylation. Vitamin C can modulate embryonic stem cell (ESC) function, enhance reprogramming of fibroblasts to induced pluripotent stem cells (iPSCs), and hinder the aberrant self-renewal of hematopoietic stem cells (HSCs) through its ability to enhance the activity of either Jumonji C (JmjC) domain-containing histone demethylases or ten-eleven translocation (TET) DNA hydroxylases. Given that epigenetic dysregulation is a known driver of malignancy, vitamin C may play a novel role as an epigenetic anticancer agent.
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For vitamin C to have a therapeutic impact on cancer, it should be given intravenously to achieve plasma levels in mM.
“For vitamin C to have a therapeutic impact on cancer, it should be given intravenously to achieve plasma levels in mM.”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [103]
The “High-dose vitamin C as an anticancer agent” section says IV administration can produce plasma levels up to 30 mM and reports anticancer efficacy with high-dose IV treatment, whereas oral dosing cannot reach those levels. But the claim makes IV delivery sound necessary for any therapeutic impact: the “Vitamin C as an adjuvant for cancer therapy” section also says restoring physiological levels can slow malignant cell growth. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe intracellular concentration of vitamin C should be relatively high for optimal function of 2OGO enzymes since Km for vitamin C ranges from 140 to 300 μM.
“Moreover, the intracellular concentration of vitamin C should be apparently relatively high for the optimal function of these enzymes since Km for vitamin C ranges from 140 to 300 µM [103].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [103]
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Antioxidants as an Epidermal Stem Cell Activator
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Vitamin C protects early mouse embryos against juglone toxicity
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- Authors
- Cimmino, L., Neel, B. G., & Aifantis, I.
- Affiliations
- NYU Langone’s Laura and Isaac Perlmutter Cancer Center (US)
- Corresponding author
- Cimmino, Luisa
- Aifantis, Iannis
- Venue
- Trends in Cell Biology
- Publisher
- Elsevier BV
- Published
- 2018-09
- Volume
- 28
- Issue
- 9
- Pages
- 698-708
- ISSN
- 0962-8924 (ISSN-L)
- PMC
- PMC6102081
- OpenAlex
- W2801924666
- Cited by
- 197
- References
- 87
- Citations by year
- 2026: 13 · 2025: 13 · 2024: 23 · 2023: 28 · 2022: 29 · 2021: 31 · 2020: 34 · 2019: 20 · 2018: 5
- FWCI
- 2.91
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Trends in Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA194923, R01CA049152, R01CA149655, R01CA133379, R01CA216421, R01CA169784, R01CA173636, P30CA016087)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- vitamin C, stem cell reprogramming, induced pluripotent stem cells, embryonic stem cells, hematopoietic stem cells, histone demethylase, Jumonji C domain, epigenetic regulation, DNA methylation, histone methylation, cancer epigenetics, fibroblast reprogramming
- MeSH terms
- Animals, Antioxidants, Ascorbic Acid, Humans, Neoplasms, Stem Cells, Epigenesis, Genetic, Cellular Reprogramming
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