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

Domenico Mastrangelo, Elvira Pelosi, Germana Castelli, Francesco Lo-Coco, Ugo Testa

Research output: Contribution to journalReview articlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)57-64
Number of pages8
JournalBlood Cells, Molecules, and Diseases
Volume69
DOIs
Publication statusE-pub ahead of print - Sep 21 2017

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Hematology
  • Cell Biology

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