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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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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. |
format | Online Article Text |
id | pubmed-6384696 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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