The role of vitamin C in epigenetic cancer therapy
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The role of vitamin C in epigenetic cancer therapy. / Mikkelsen, Stine Ulrik; Gillberg, Linn; Lykkesfeldt, Jens; Grønbæk, Kirsten.
In: Free Radical Biology and Medicine, Vol. 170, 2021, p. 179-193.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The role of vitamin C in epigenetic cancer therapy
AU - Mikkelsen, Stine Ulrik
AU - Gillberg, Linn
AU - Lykkesfeldt, Jens
AU - Grønbæk, Kirsten
N1 - Publisher Copyright: © 2021 Elsevier Inc.
PY - 2021
Y1 - 2021
N2 - The role of vitamin C in the treatment of cancer has been subject to controversy for decades. Within the past 10 years, mechanistic insight into the importance of vitamin C in epigenetic regulation has provided a new rationale for its potential anti-cancer effects. At physiological concentrations, vitamin C is a potent antioxidant and thereby co-factor for a range of enzymes including the Fe(II)- and α-ketoglutarate-dependent dioxygenases that represent some of the most important epigenetic regulators; the ten-eleven translocation (TET) methylcytosine dioxygenases and the Jumonji-C domain-containing histone demethylases. Epigenetic deregulation is a hallmark of many cancers and reduced activity of these enzymes or somatic loss-of-function mutations in the genes encoding them, are observed in many cancer types. The present review outlines the growing literature on the role of vitamin C in epigenetic therapy of cancer. In the vast majority of in vitro, animal and clinical studies included in this review, vitamin C showed ability across cancer types to increase the hydroxylation of 5-methylcytosine to 5-hydroxymethylcytosine catalyzed by the TET enzymes - the first step in DNA demethylation. Most consistently, vitamin C in combination with the class of epigenetic drugs, DNA methyltransferase inhibitors, has demonstrated efficacy in the treatment of hematological malignancies in both preclinical and the limited number of available clinical studies. Yet, the pertinent question of what is the optimal dose of vitamin C in cancer studies remains to be answered. High-quality randomized placebo-controlled trials are needed to determine whether supplementation with vitamin C may benefit subgroups of patients with (pre-)cancer.
AB - The role of vitamin C in the treatment of cancer has been subject to controversy for decades. Within the past 10 years, mechanistic insight into the importance of vitamin C in epigenetic regulation has provided a new rationale for its potential anti-cancer effects. At physiological concentrations, vitamin C is a potent antioxidant and thereby co-factor for a range of enzymes including the Fe(II)- and α-ketoglutarate-dependent dioxygenases that represent some of the most important epigenetic regulators; the ten-eleven translocation (TET) methylcytosine dioxygenases and the Jumonji-C domain-containing histone demethylases. Epigenetic deregulation is a hallmark of many cancers and reduced activity of these enzymes or somatic loss-of-function mutations in the genes encoding them, are observed in many cancer types. The present review outlines the growing literature on the role of vitamin C in epigenetic therapy of cancer. In the vast majority of in vitro, animal and clinical studies included in this review, vitamin C showed ability across cancer types to increase the hydroxylation of 5-methylcytosine to 5-hydroxymethylcytosine catalyzed by the TET enzymes - the first step in DNA demethylation. Most consistently, vitamin C in combination with the class of epigenetic drugs, DNA methyltransferase inhibitors, has demonstrated efficacy in the treatment of hematological malignancies in both preclinical and the limited number of available clinical studies. Yet, the pertinent question of what is the optimal dose of vitamin C in cancer studies remains to be answered. High-quality randomized placebo-controlled trials are needed to determine whether supplementation with vitamin C may benefit subgroups of patients with (pre-)cancer.
UR - http://www.scopus.com/inward/record.url?scp=85104453411&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2021.03.017
DO - 10.1016/j.freeradbiomed.2021.03.017
M3 - Journal article
C2 - 33789122
AN - SCOPUS:85104453411
VL - 170
SP - 179
EP - 193
JO - Free Radical Biology & Medicine
JF - Free Radical Biology & Medicine
SN - 0891-5849
ER -
ID: 273070384