Utilization of Pharmacological Ascorbate to Enhance Hydrogen Peroxide-Mediated Radiosensitivity in Cancer Therapy

Int J Mol Sci. 2021 Oct 8;22(19):10880. doi: 10.3390/ijms221910880.

Abstract

Interest in the use of pharmacological ascorbate as a treatment for cancer has increased considerably since it was introduced by Cameron and Pauling in the 1970s. Recently, pharmacological ascorbate has been used in preclinical and early-phase clinical trials as a selective radiation sensitizer in cancer. The results of these studies are promising. This review summarizes data on pharmacological ascorbate (1) as a safe and efficacious adjuvant to cancer therapy; (2) as a selective radiosensitizer of cancer via a mechanism involving hydrogen peroxide; and (3) as a radioprotector in normal tissues. Additionally, we present new data demonstrating the ability of pharmacological ascorbate to enhance radiation-induced DNA damage in glioblastoma cells, facilitating cancer cell death. We propose that pharmacological ascorbate may be a general radiosensitizer in cancer therapy and simultaneously a radioprotector of normal tissue.

Keywords: hydrogen peroxide; pharmacological ascorbate; radiation therapy; radiosensitization; reactive oxygen species.

Publication types

  • Review

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Ascorbic Acid / pharmacology*
  • Humans
  • Hydrogen Peroxide / pharmacology*
  • Neoplasms / drug therapy
  • Neoplasms / pathology
  • Neoplasms / radiotherapy*
  • Oxidants / pharmacology
  • Oxidative Stress / drug effects*
  • Radiation Tolerance / drug effects*
  • Radiation-Sensitizing Agents / pharmacology*
  • Reactive Oxygen Species / metabolism

Substances

  • Antioxidants
  • Oxidants
  • Radiation-Sensitizing Agents
  • Reactive Oxygen Species
  • Hydrogen Peroxide
  • Ascorbic Acid