The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Vitamin C increases viral mimicry induced by 5-aza-2′-deoxycytidine
Open accessAbstract
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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“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]
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“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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Cites
1 retracted
Ghoshal, K., Datta, J., Majumder, S., Bai, S., Kutay, H., Motiwala, T., & Jacob, S. T. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.11.4727-4741.2005 · Cited by 444
RetractedConversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by MLL Partner TET1
Tahiliani, M., Koh, K. P., Shen, Y., Pastor, W. A., Bandukwala, H., Brudno, Y., Agarwal, S., Iyer, L. M., Liu, D. R., Aravind, L., et al. (2009) · Science · doi:10.1126/science.1170116 · Cited by 5,836
Chou, T.-C. (2006) · Pharmacological Reviews · doi:10.1124/pr.58.3.10 · Cited by 5,163
Genetic Basis for Clinical Response to CTLA-4 Blockade in Melanoma
Snyder, A., Makarov, V., Merghoub, T., Yuan, J., Zaretsky, J. M., Desrichard, A., Walsh, L. A., Postow, M. A., Wong, P., Ho, T. S., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1406498 · Cited by 4,286
Epigenetics in human disease and prospects for epigenetic therapy
Egger, G., Liang, G., Aparicio, A., & Jones, P. A. (2004) · Nature · doi:10.1038/nature02625 · Cited by 3,232
Self-citationA decade of exploring the cancer epigenome—biological and translational implications
Baylin, S. B., & Jones, P. A. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3130 · Cited by 2,871
Self-citationFenaux, P., Mufti, G. J., Hellstrom-Lindberg, E., Santini, V., Finelli, C., Giagounidis, A., Schoch, R., Gattermann, N., Sanz, G., List, A., et al. (2009) · The Lancet Oncology · doi:10.1016/s1470-2045(09)70003-8 · Cited by 2,663
Chiappinelli, K. B., Strissel, P. L., Desrichard, A., Li, H., Henke, C., Akman, B., Hein, A., Rote, N. S., Cope, L. M., Snyder, A., et al. (2015) · Cell · doi:10.1016/j.cell.2015.07.011 · Cited by 2,022
Self-citationDecitabine improves patient outcomes in myelodysplastic syndromes
Kantarjian, H. M., Issa, J. J., Rosenfeld, C. S., Bennett, J. M., Albitar, M. X., DiPersio, J. F., Klimek, V. M., Slack, J. L., de Castro, C., Ravandi, F., et al. (2006) · Cancer · doi:10.1002/cncr.21792 · Cited by 1,539
Roulois, D., Loo Yau, H., Singhania, R., Wang, Y., Danesh, A., Shen, S. Y., Han, H., Liang, G., Jones, P. A., Pugh, T. J., et al. (2015) · Cell · doi:10.1016/j.cell.2015.07.056 · Cited by 1,527
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Restoration of TET2 Function Blocks Aberrant Self-Renewal and Leukemia Progression
Cimmino, L., Dolgalev, I., Wang, Y., Yoshimi, A., Martin, G. H., Wang, J., Ng, V., Xia, B., Witkowski, M. T., Mitchell-Flack, M., et al. (2017) · Cell · doi:10.1016/j.cell.2017.07.032 · Cited by 707
Epigenetic therapy in immune-oncology
Jones, P. A., Ohtani, H., Chakravarthy, A., & Carvalho, D. D. D. (2019) · Nature reviews. Cancer · doi:10.1038/s41568-019-0109-9 · Cited by 559
Self-citationAscorbate regulates haematopoietic stem cell function and leukaemogenesis
Agathocleous, M., Meacham, C. E., Burgess, R. J., Piskounova, E., Zhao, Z., Crane, G. M., Cowin, B. L., Bruner, E., Murphy, M. M., Chen, W., et al. (2017) · Nature · doi:10.1038/nature23876 · Cited by 545
“Humans with haematological malignancies have significantly lower serum ascorbate levels as compared to healthy controls 40,41 .”
Targeting cancer vulnerabilities with high-dose vitamin C
Ngo, B., Van Riper, J. M., Cantley, L. C., & Yun, J. (2019) · Nature Reviews Cancer · doi:10.1038/s41568-019-0135-7 · Cited by 423
Epigenetics-targeted drugs: current paradigms and future challenges
Dai, W., Qiao, X., Fang, Y., Guo, R., Bai, P., Liu, S., Li, T., Jiang, Y., Wei, S., Na, Z., et al. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02039-0 · Cited by 405
Metadata
- 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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