Journal
CANCER CELL
Volume 34, Issue 5, Pages 700-706Publisher
CELL PRESS
DOI: 10.1016/j.ccell.2018.07.014
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Funding
- NIDDK, NIH [Z01-DK053212-12, Z01-DK053218-12, Z01-DK054506-21]
- American Society of Hematology Research Training Award for Fellows
- University of Iowa/Mayo Clinic Lymphoma [SPORE CA97274]
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Vitamin C (ascorbic acid, ascorbate), despite controversy, has re-emerged as a promising anti-cancer agent. Recent knowledge of intravenous ascorbate pharmacokinetics and discovery of unexpected mechanisms of ascorbate action have spawned many investigations. Two mechanisms of anti-cancer activity with ascorbate have gained prominence: hydrogen peroxide-induced oxidative stress and DNA demethylation mediated by ten-eleven translocation enzyme activation. Here, we highlight salient aspects of the evolution of ascorbate in cancer treatment, provide insights into the pharmacokinetics of ascorbate, describe mechanisms of its anti-cancer activity in relation to the pharmacokinetics, outline promising preclinical and clinical evidence, and recommend future directions.
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