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 article

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 & diseases
Volume69
DOIs
Publication statusPublished - Mar 2018

Fingerprint

Epigenomics
Neoplasms
Biochemical Phenomena
Dioxygenases
Prodrugs
Enzymes
Vitamins
Hydrogen Peroxide
Ascorbic Acid
Oxidation-Reduction
Oxidative Stress
Therapeutics
Gene Expression
Food
Injections
Clinical Studies

Keywords

  • Animals
  • Antineoplastic Agents/chemistry
  • Apoptosis/drug effects
  • Ascorbic Acid/chemistry
  • Cell Proliferation/drug effects
  • DNA Methylation
  • DNA Modification Methylases/genetics
  • Epigenesis, Genetic/drug effects
  • Gene Expression Regulation, Neoplastic/drug effects
  • Histone Demethylases/genetics
  • Humans
  • Neoplasms/drug therapy

Cite this

Mechanisms of anti-cancer effects of ascorbate : Cytotoxic activity and epigenetic modulation. / Mastrangelo, Domenico; Pelosi, Elvira; Castelli, Germana; Lo-Coco, Francesco; Testa, Ugo.

In: Blood cells, molecules & diseases, Vol. 69, 03.2018, p. 57-64.

Research output: Contribution to journalReview article

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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.",
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AU - Mastrangelo, Domenico

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N2 - 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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