Two Faces of Vitamin C—Antioxidative and Pro-Oxidative Agent

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Abstract

Vitamin C has been known for decades. It is common in everyday use as an element of the diet, supplementation, and a preservative. For years, research has been conducted to precisely determine the mechanism of action of ascorbate in the cell. Available results indicate its multi-directional cellular effects. Vitamin C, which belongs to antioxidants scavenging free radicals, also has a ‘second face’—as a pro-oxidative factor. However, whether is the latter nature a defect harmful to the cell, or whether a virtue that is a source of benefit? In this review, we discuss the effects of vitamin C treatment in cancer prevention and the role of ascorbate in maintaining redox balance in the central nervous system (CNS). Finally, we discuss the effect of vitamin C supplementation on biomarkers of oxidative DNA damage and review the evidence that vitamin C has radioprotective properties.

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Iron and cancer: more ore to be mined.

Suzy Torti, Frank Torti (2013)

Iron is an essential nutrient that facilitates cell proliferation and growth. However, iron also has the capacity to engage in redox cycling and free radical formation. Therefore, iron can contribute to both tumour initiation and tumour growth; recent work has also shown that iron has a role in the tumour microenvironment and in metastasis. Pathways of iron acquisition, efflux, storage and regulation are all perturbed in cancer, suggesting that reprogramming of iron metabolism is a central aspect of tumour cell survival. Signalling through hypoxia-inducible factor (HIF) and WNT pathways may contribute to altered iron metabolism in cancer. Targeting iron metabolic pathways may provide new tools for cancer prognosis and therapy.

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Hypoxia and metabolic adaptation of cancer cells

K L Eales, K E R Hollinshead, D A Tennant (2016)

Low oxygen tension (hypoxia) is a pervasive physiological and pathophysiological stimulus that metazoan organisms have contended with since they evolved from their single-celled ancestors. The effect of hypoxia on a tissue can be either positive or negative, depending on the severity, duration and context. Over the long-term, hypoxia is not usually consistent with normal function and so multicellular organisms have had to evolve both systemic and cellular responses to hypoxia. Our reliance on oxygen for efficient adenosine triphosphate (ATP) generation has meant that the cellular metabolic network is particularly sensitive to alterations in oxygen tension. Metabolic changes in response to hypoxia are elicited through both direct mechanisms, such as the reduction in ATP generation by oxidative phosphorylation or inhibition of fatty-acid desaturation, and indirect mechanisms including changes in isozyme expression through hypoxia-responsive transcription factor activity. Significant regions of cancers often grow in hypoxic conditions owing to the lack of a functional vasculature. As hypoxic tumour areas contain some of the most malignant cells, it is important that we understand the role metabolism has in keeping these cells alive. This review will outline our current understanding of many of the hypoxia-induced changes in cancer cell metabolism, how they are affected by other genetic defects often present in cancers, and how these metabolic alterations support the malignant hypoxic phenotype.

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Ascorbic acid: chemistry, biology and the treatment of cancer.

Juan Du, Joseph Cullen, Garry Buettner (2012)

Since the discovery of vitamin C, the number of its known biological functions is continually expanding. Both the names ascorbic acid and vitamin C reflect its antiscorbutic properties due to its role in the synthesis of collagen in connective tissues. Ascorbate acts as an electron-donor keeping iron in the ferrous state thereby maintaining the full activity of collagen hydroxylases; parallel reactions with a variety of dioxygenases affect the expression of a wide array of genes, for example via the HIF system, as well as via the epigenetic landscape of cells and tissues. In fact, all known physiological and biochemical functions of ascorbate are due to its action as an electron donor. The ability to donate one or two electrons makes AscH(-) an excellent reducing agent and antioxidant. Ascorbate readily undergoes pH-dependent autoxidation producing hydrogen peroxide (H(2)O(2)). In the presence of catalytic metals this oxidation is accelerated. In this review, we show that the chemical and biochemical nature of ascorbate contribute to its antioxidant as well as its prooxidant properties. Recent pharmacokinetic data indicate that intravenous (i.v.) administration of ascorbate bypasses the tight control of the gut producing highly elevated plasma levels; ascorbate at very high levels can act as prodrug to deliver a significant flux of H(2)O(2) to tumors. This new knowledge has rekindled interest and spurred new research into the clinical potential of pharmacological ascorbate. Knowledge and understanding of the mechanisms of action of pharmacological ascorbate bring a rationale to its use to treat disease especially the use of i.v. delivery of pharmacological ascorbate as an adjuvant in the treatment of cancer. Published by Elsevier B.V.

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Journal

Journal ID (nlm-ta): Nutrients

Journal ID (iso-abbrev): Nutrients

Journal ID (publisher-id): nutrients

Title: Nutrients

Publisher: MDPI

ISSN (Electronic): 2072-6643

Publication date (Electronic): 21 May 2020

Publication date Collection: May 2020

Volume: 12

Issue: 5

Electronic Location Identifier: 1501

Affiliations

DNA Damage Laboratory of Food Science Department, Faculty of Pharmacy, Medical University of Lodz, ul. Muszynskiego 1, 90-151 Lodz, Poland; julia.kazmierczak-baranska@ 123456umed.lodz.pl (J.K.-B.); karolina.boguszewska@ 123456umed.lodz.pl (K.B.); angelika.adamus@ 123456umed.lodz.pl (A.A.-G.)

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[* ]Correspondence: boleslaw.karwowski@ 123456umed.lodz.pl ; Tel.: +48-42-677-91-40

Author information

Julia Kaźmierczak-Barańska https://orcid.org/0000-0001-8560-5727

Angelika Adamus-Grabicka https://orcid.org/0000-0003-0119-599X

Bolesław T. Karwowski https://orcid.org/0000-0001-6922-7834

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Publisher ID: nutrients-12-01501

DOI: 10.3390/nu12051501

PMC ID: 7285147

PubMed ID: 32455696

SO-VID: 990817a5-752d-4c0f-8ad1-ccb7cf0734a2

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Two Faces of Vitamin C—Antioxidative and Pro-Oxidative Agent

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Most cited references 97

Iron and cancer: more ore to be mined.

Hypoxia and metabolic adaptation of cancer cells

Ascorbic acid: chemistry, biology and the treatment of cancer.

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