New potential biomarker for stratification of patients for pharmacological vitamin C in adjuvant settings of cancer therapy

Redox Biol. 2020 Jan;28:101357. doi: 10.1016/j.redox.2019.101357. Epub 2019 Oct 23.

Abstract

Our graphical review expands the analysis of cancer vulnerabilities for high dose vitamin C, based on several facts, illustrating the cytotoxic potential of the ascorbate free radical (AFR) via impairment of mitochondrial respiration and the mechanisms of its elimination in mammals by the membrane-bound NADH:cytochrome b5 oxidoreductase 3 (Cyb5R3). We propose that vitamin C can function in "protective mode" or "destructive mode" affecting cellular homeostasis, depending on the intracellular "steady-state" concentration of AFR and differential expression/activity of Cyb5R3 in cancerous and normal cells. Thus, a specific anti-cancer effect can be achieved at high doses of vitamin C therapy. The review is intended for a wide audience of readers - from students to specialists in the field.

Keywords: Ascorbate free radical; Cancer; Mitochondria; NADH:Cytochrome b5 oxidoreductase 3; Redox signaling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Ascorbic Acid / adverse effects*
  • Ascorbic Acid / chemistry
  • Ascorbic Acid / therapeutic use
  • Biomarkers, Tumor / metabolism
  • Chemotherapy, Adjuvant
  • Cytochrome-B(5) Reductase / metabolism
  • Free Radicals / metabolism*
  • Homeostasis / drug effects
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism

Substances

  • Biomarkers, Tumor
  • Free Radicals
  • CYB5R3 protein, human
  • Cytochrome-B(5) Reductase
  • Ascorbic Acid