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Vitamin C as a Modulator of the Response to Cancer Therapy

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 c...

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Autores principales: Blaszczak, Wiktoria, Barczak, Wojciech, Masternak, Julia, Kopczyński, Przemysław, Zhitkovich, Anatoly, Rubiś, Błażej
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6384696/
https://www.ncbi.nlm.nih.gov/pubmed/30695991
http://dx.doi.org/10.3390/molecules24030453
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author Blaszczak, Wiktoria
Barczak, Wojciech
Masternak, Julia
Kopczyński, Przemysław
Zhitkovich, Anatoly
Rubiś, Błażej
author_facet Blaszczak, Wiktoria
Barczak, Wojciech
Masternak, Julia
Kopczyński, Przemysław
Zhitkovich, Anatoly
Rubiś, Błażej
author_sort Blaszczak, Wiktoria
collection PubMed
description 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.
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spelling pubmed-63846962019-02-23 Vitamin C as a Modulator of the Response to Cancer Therapy Blaszczak, Wiktoria Barczak, Wojciech Masternak, Julia Kopczyński, Przemysław Zhitkovich, Anatoly Rubiś, Błażej Molecules Review 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. MDPI 2019-01-28 /pmc/articles/PMC6384696/ /pubmed/30695991 http://dx.doi.org/10.3390/molecules24030453 Text en © 2019 by the authors. 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/).
spellingShingle Review
Blaszczak, Wiktoria
Barczak, Wojciech
Masternak, Julia
Kopczyński, Przemysław
Zhitkovich, Anatoly
Rubiś, Błażej
Vitamin C as a Modulator of the Response to Cancer Therapy
title Vitamin C as a Modulator of the Response to Cancer Therapy
title_full Vitamin C as a Modulator of the Response to Cancer Therapy
title_fullStr Vitamin C as a Modulator of the Response to Cancer Therapy
title_full_unstemmed Vitamin C as a Modulator of the Response to Cancer Therapy
title_short Vitamin C as a Modulator of the Response to Cancer Therapy
title_sort vitamin c as a modulator of the response to cancer therapy
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6384696/
https://www.ncbi.nlm.nih.gov/pubmed/30695991
http://dx.doi.org/10.3390/molecules24030453
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