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Blood Cells Mol Dis. 2018 Mar;69:57-64. doi: 10.1016/j.bcmd.2017.09.005. Epub 2017 Sep 21.

Mechanisms of anti-cancer effects of ascorbate: Cytotoxic activity and epigenetic modulation.

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Department of Medical, Surgical and Neurological Sciences, University of Siena, Polo Scientifico San Miniato, Siena, Italy.
Department of Oncology, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy; Santa Lucia Foundation, I.R.C.C.S., Via del Fosso di Fiorano, Rome, Italy.
Department of Oncology, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. Electronic address:


Vitamin C (Vit C or Ascorbate) is essential for many fundamental biochemical processes. Vit C is an essential nutrient with redox functions at normal physiologic concentrations. The main physiologic function of this vitamin is related to its capacity to act as a co-factor for a large family of enzymes, collectively known as Fe and 2-oxoglutarate-dependent dioxygenases. It also modulates epigenetic gene expression through the control of TET enzymes activity. Vit C also has several biological properties allowing to restore the deregulated epigenetic response observed in many tumors. High-dose Vit C has been investigated as a treatment for cancer patients since the 1969. Pharmacologic ascorbate acts as a pro-drug for hydrogen peroxide formation (H2O2) and, through this mechanism, kills cancer cells. To achieve high in vivo concentrations, Ascorbate must be injected by i.v. route. Initial clinical studies of Ascorbate cancer treatment have provided encouraging results, not confirmed in subsequent studies. Recent clinical studies using i.v. injection of high-dose Ascorbate have renewed the interest in the field, showing that significant anti-tumor activity. Pre-clinical studies have led to identify tumors sensitive to Ascorbate that could potentially benefit from this treatment either through an epigenetic modulator effect or through tumor killing by oxidative stress.

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