RRC ID 67703
Author Uetaki M, Tabata S, Nakasuka F, Soga T, Tomita M.
Title Metabolomic alterations in human cancer cells by vitamin C-induced oxidative stress.
Journal Sci Rep
Abstract 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.
Volume 5
Pages 13896
Published 2015-9-9
DOI 10.1038/srep13896
PII srep13896
PMID 26350063
PMC PMC4563566
MeSH Ascorbic Acid / metabolism* Ascorbic Acid / pharmacology Ascorbic Acid / toxicity Cell Survival / drug effects Energy Metabolism / drug effects Humans Hydrogen Peroxide / metabolism MCF-7 Cells Metabolome* Metabolomics* / methods NAD / metabolism Neoplasms / metabolism* Oxidative Stress* / drug effects
IF 3.998
Human and Animal Cells PANC-1(RCB2095)