TY - JOUR

T1 - Vitamin C - A new player in regulation of the cancer epigenome

AU - Gillberg, Linn

AU - Ørskov, Andreas D.

AU - Liu, Minmin

AU - Harsløf, Laurine B.S.

AU - Jones, Peter A.

AU - Grønbæk, Kirsten

PY - 2018/8

Y1 - 2018/8

N2 - Over the past few years it has become clear that vitamin C, as a provider of reduced iron, is an essential factor for the function of epigenetic regulators that initiate the demethylation of DNA and histones. Vitamin C deficiency is rare in the general population, but is frequently observed in patients with cancer. Genes encoding epigenetic regulators are often mutated in cancer, underscoring their central roles in carcinogenesis. In hematological cancers, such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), drugs that reverse epigenetic aberrations are now the standard of care. Recent in vitro studies suggest that vitamin C at physiological concentrations, combined with hypomethylating agents may act synergistically to cause DNA demethylation through active and passive mechanisms, respectively. Additionally, several recent studies have renewed interest in the use of pharmacological doses of vitamin C injected intravenously to selectively kill tumor cells. This review will focus on the potential of vitamin C to optimize the outcome of epigenetic therapy in cancer patients and alternatively to act as a therapeutic at high doses.

AB - Over the past few years it has become clear that vitamin C, as a provider of reduced iron, is an essential factor for the function of epigenetic regulators that initiate the demethylation of DNA and histones. Vitamin C deficiency is rare in the general population, but is frequently observed in patients with cancer. Genes encoding epigenetic regulators are often mutated in cancer, underscoring their central roles in carcinogenesis. In hematological cancers, such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), drugs that reverse epigenetic aberrations are now the standard of care. Recent in vitro studies suggest that vitamin C at physiological concentrations, combined with hypomethylating agents may act synergistically to cause DNA demethylation through active and passive mechanisms, respectively. Additionally, several recent studies have renewed interest in the use of pharmacological doses of vitamin C injected intravenously to selectively kill tumor cells. This review will focus on the potential of vitamin C to optimize the outcome of epigenetic therapy in cancer patients and alternatively to act as a therapeutic at high doses.

KW - Ascorbic acid

KW - Cancer treatment

KW - Epigenetics

KW - Hematological malignancies

KW - Vitamin C

UR - http://www.scopus.com/inward/record.url?scp=85035215953&partnerID=8YFLogxK

U2 - 10.1016/j.semcancer.2017.11.001

DO - 10.1016/j.semcancer.2017.11.001

M3 - Review

C2 - 29102482

AN - SCOPUS:85035215953

VL - 51

SP - 59

EP - 67

JO - Seminars in Cancer Biology

JF - Seminars in Cancer Biology

SN - 1044-579X

ER -