Vitamin C increases viral mimicry induced by 5-aza-2′-deoxycytidine
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Significance: Our work shows a remarkable synergy between physiological levels of vitamin C and 5-aza-CdR. The combination enhances the viral mimicry response to DNA methyltransferase inhibitors, including the upregulation of endogenous retroviruses in the dsRNA form and the induction of viral defense pathways. Because patients with hematological and other cancers are often markedly vitamin C deficient, the addition of vitamin C to treatment protocols may be a straightforward way to increase the clinical efficacy of such drugs in patients with myelodysplastic syndrome and leukemia.
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Vitamin C boosted decitabine's action by increasing demethylation of human endogenous retroviruses and interferon-stimulated gene expression, causing cancer cells to die.
“For example, on the basis of ascorbate’s known DNA demethylation effects via TET activation, a recent study found that vitamin C enhanced the effect of the DNMT inhibitor 5-aza-CdR (decitabine) by promoting the demethylation of human endogenous retroviruses and amplifying the expression of interferon-stimulated genes, leading to cancer cell death106,107.”
From Targeting cancer vulnerabilities with high-dose vitamin C (2019) · cites this paper as [106]
A recent report in a small cohort of patients (n=24) with haematological malignancies showed that >90% had decreased plasma vitamin C concentrations and 58% were classified as vitamin C deficient.
“Interestingly, a recent report in a small cohort of patients (n=24) with haematological malignancies showed that >90% had decreased plasma vitamin C concentrations and 58% were classified as vitamin C deficient.56”
From Vitamin C-induced epigenomic remodelling in IDH1 mutant acute myeloid leukaemia (2018) · cites this paper as [56]
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- Authors
- Liu, M., Ohtani, H., Zhou, W., Ørskov, A. D., Charlet, J., Zhang, Y. W., Shen, H., Baylin, S. B., Liang, G., Grønbæk, K., & Jones, P. A.
- Affiliations
- Van Andel Institute (US)
- Rigshospitalet (DK)
- University of Southern California (US)
- Johns Hopkins University (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-08-29
- Volume
- 113
- Issue
- 37
- Pages
- 10238-10244
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5027469
- OpenAlex
- W2507387671
- Cited by
- 225
- References
- 49
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 16 · 2023: 28 · 2022: 32 · 2021: 41 · 2020: 19 · 2019: 23 · 2018: 24 · 2017: 21 · 2016: 2
- FWCI
- 12.12
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- Funders
- HHS | NIH | National Cancer Institute (R01CA082422)
- American Association for Cancer Research (Stand Up To Cancer Epigenetics Dream Team)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- scurvy, decitabine, hypomethylating agents, hematologic malignancies, endogenous retroviruses, viral mimicry, TET2, 5-hydroxymethylcytosine, 5-methylcytosine, interferon response, apoptosis, epigenetic therapy, vitamin C supplementation
- MeSH terms
- Decitabine, Ascorbic Acid, Ascorbic Acid Deficiency, Azacitidine, DNA-Binding Proteins, Drug Synergism, Enzyme Inhibitors, Female, Humans, Interferons, Male, Methyltransferases, Proto-Oncogene Proteins, RNA, Double-Stranded, Apoptosis, DNA Methylation, Hematologic Neoplasms, Endogenous Retroviruses, Cell Proliferation, Dioxygenases
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