Vitamin C as a Modulator of the Response to Cancer Therapy

Molecules. 2019 Jan 28;24(3):453. doi: 10.3390/molecules24030453.


Ascorbic acid (vitamin C) has been gaining attention as a potential treatment for human malignancies. Various experimental studies have shown the ability of pharmacological doses of vitamin C alone or in combinations with clinically used drugs to exert beneficial effects in various models of human cancers. Cytotoxicity of high doses of vitamin C in cancer cells appears to be related to excessive reactive oxygen species generation and the resulting suppression of the energy production via glycolysis. A hallmark of cancer cells is a strongly upregulated aerobic glycolysis, which elevates its relative importance as a source of ATP (Adenosine 5'-triphosphate). Aerobic glycolysis is maintained by a highly increased uptake of glucose, which is made possible by the upregulated expression of its transporters, such as GLUT-1, GLUT-3, and GLUT-4. These proteins can also transport the oxidized form of vitamin C, dehydroascorbate, permitting its preferential uptake by cancer cells with the subsequent depletion of critical cellular reducers as a result of ascorbate formation. Ascorbate also has a potential to affect other aspects of cancer cell metabolism due to its ability to promote reduction of iron(III) to iron(II) in numerous cellular metalloenzymes. Among iron-dependent dioxygenases, important targets for stimulation by vitamin C in cancer include prolyl hydroxylases targeting the hypoxia-inducible factors HIF-1/HIF-2 and histone and DNA demethylases. Altered metabolism of cancer cells by vitamin C can be beneficial by itself and promote activity of specific drugs.

Keywords: ROS; ascorbate; cancer; cancer therapy; chemotherapy; hypoxia; oxidative stress; vitamin C.

Publication types

  • Review

MeSH terms

  • Animals
  • Ascorbic Acid / pharmacology*
  • Ascorbic Acid / therapeutic use*
  • Combined Modality Therapy
  • Drug Synergism
  • Humans
  • Hypoxia / drug therapy
  • Hypoxia / genetics
  • Hypoxia / metabolism
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / therapy*
  • Oxidation-Reduction / drug effects
  • Oxidative Stress / drug effects
  • Reactive Oxygen Species / metabolism
  • Treatment Outcome


  • Reactive Oxygen Species
  • Ascorbic Acid