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Metabolomic alterations in human cancer cells by vitamin C-induced oxidative stress
Intravenous administration of high-dose vitamin C has recently attracted attention as a cancer therapy. High-dose vitamin C induces pro-oxidant effects and selectively kills cancer cells. However, the anticancer mechanisms of vitamin C are not fully understood. Here, we analyzed metabolic changes in...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4563566/ https://www.ncbi.nlm.nih.gov/pubmed/26350063 http://dx.doi.org/10.1038/srep13896 |
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author | Uetaki, Megumi Tabata, Sho Nakasuka, Fumie Soga, Tomoyoshi Tomita, Masaru |
author_facet | Uetaki, Megumi Tabata, Sho Nakasuka, Fumie Soga, Tomoyoshi Tomita, Masaru |
author_sort | Uetaki, Megumi |
collection | PubMed |
description | Intravenous administration of high-dose vitamin C has recently attracted attention as a cancer therapy. High-dose vitamin C induces pro-oxidant effects and selectively kills cancer cells. However, the anticancer mechanisms of vitamin C are not fully understood. Here, we analyzed metabolic changes induced by vitamin C in MCF7 human breast adenocarcinoma and HT29 human colon cancer cells using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). The metabolomic profiles of both cell lines were dramatically altered after exposure to cytotoxic concentrations of vitamin C. Levels of upstream metabolites in the glycolysis pathway and tricarboxylic acid (TCA) cycle were increased in both cell lines following treatment with vitamin C, while adenosine triphosphate (ATP) levels and adenylate energy charges were decreased concentration-dependently. Treatment with N-acetyl cysteine (NAC) and reduced glutathione (GSH) significantly inhibited vitamin C-induced cytotoxicity in MCF7 cells. NAC also suppressed vitamin C-dependent metabolic changes, and NAD treatment prevented vitamin C-induced cell death. Collectively, our data suggests that vitamin C inhibited energy metabolism through NAD depletion, thereby inducing cancer cell death. |
format | Online Article Text |
id | pubmed-4563566 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-45635662015-09-15 Metabolomic alterations in human cancer cells by vitamin C-induced oxidative stress Uetaki, Megumi Tabata, Sho Nakasuka, Fumie Soga, Tomoyoshi Tomita, Masaru Sci Rep Article Intravenous administration of high-dose vitamin C has recently attracted attention as a cancer therapy. High-dose vitamin C induces pro-oxidant effects and selectively kills cancer cells. However, the anticancer mechanisms of vitamin C are not fully understood. Here, we analyzed metabolic changes induced by vitamin C in MCF7 human breast adenocarcinoma and HT29 human colon cancer cells using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). The metabolomic profiles of both cell lines were dramatically altered after exposure to cytotoxic concentrations of vitamin C. Levels of upstream metabolites in the glycolysis pathway and tricarboxylic acid (TCA) cycle were increased in both cell lines following treatment with vitamin C, while adenosine triphosphate (ATP) levels and adenylate energy charges were decreased concentration-dependently. Treatment with N-acetyl cysteine (NAC) and reduced glutathione (GSH) significantly inhibited vitamin C-induced cytotoxicity in MCF7 cells. NAC also suppressed vitamin C-dependent metabolic changes, and NAD treatment prevented vitamin C-induced cell death. Collectively, our data suggests that vitamin C inhibited energy metabolism through NAD depletion, thereby inducing cancer cell death. Nature Publishing Group 2015-09-09 /pmc/articles/PMC4563566/ /pubmed/26350063 http://dx.doi.org/10.1038/srep13896 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Uetaki, Megumi Tabata, Sho Nakasuka, Fumie Soga, Tomoyoshi Tomita, Masaru Metabolomic alterations in human cancer cells by vitamin C-induced oxidative stress |
title | Metabolomic alterations in human cancer cells by vitamin C-induced oxidative stress |
title_full | Metabolomic alterations in human cancer cells by vitamin C-induced oxidative stress |
title_fullStr | Metabolomic alterations in human cancer cells by vitamin C-induced oxidative stress |
title_full_unstemmed | Metabolomic alterations in human cancer cells by vitamin C-induced oxidative stress |
title_short | Metabolomic alterations in human cancer cells by vitamin C-induced oxidative stress |
title_sort | metabolomic alterations in human cancer cells by vitamin c-induced oxidative stress |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4563566/ https://www.ncbi.nlm.nih.gov/pubmed/26350063 http://dx.doi.org/10.1038/srep13896 |
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