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Molecules. 2019 Jan 28;24(3). pii: E453. doi: 10.3390/molecules24030453.

Vitamin C as a Modulator of the Response to Cancer Therapy.

Author information

1
Radiobiology Lab, The Greater Poland Cancer Centre, Garbary, 61-866 Poznan, Poland. w.z.blaszczak@gmail.com.
2
Radiobiology Lab, The Greater Poland Cancer Centre, Garbary, 61-866 Poznan, Poland. wbarczak@ump.edu.pl.
3
Department of Head and Neck Surgery, Poznan University of Medical Sciences, The Greater Poland Cancer Centre, Garbary, 61-866 Poznan, Poland. wbarczak@ump.edu.pl.
4
Department of Clinical Chemistry and Molecular Diagnostics, Poznan University of Medical Sciences, 60-355 Poznan, Poland. juliamasternak@wp.pl.
5
Centre for Orthodontic Mini-implants at the Department and Clinic of Maxillofacial Orthopedics and Orthodontics, Poznan University of Medical Sciences, 60-812 Poznan, Poland. pkopczynski@orto1.net.
6
Department of Pathology and Laboratory Medicine, Brown University, Providence, RI 02912, USA. anatoly_zhitkovich@brown.edu.
7
Department of Clinical Chemistry and Molecular Diagnostics, Poznan University of Medical Sciences, 60-355 Poznan, Poland. blazejr@ump.edu.pl.

Abstract

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

PMID:
30695991
PMCID:
PMC6384696
DOI:
10.3390/molecules24030453
[Indexed for MEDLINE]
Free PMC Article

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