Metabolomic alterations in human cancer cells by vitamin C-induced oxidative stress

• DOI: 10.1038/srep13896
• Publication Date: 2015-09-09T09:52:08Z
• Authors: Megumi Uetaki; Sho Tabata; Fumie Nakasuka; Tomoyoshi Soga; Masaru Tomita
• Keywords: 0301 basic medicine; Cell Survival; Ascorbic Acid; Hydrogen Peroxide; NAD; Article; 3. Good health; Oxidative Stress; 03 medical and health sciences; Neoplasms; MCF-7 Cells; Metabolome; Humans; Metabolomics; Energy Metabolism

Abstract Intravenous administration of high-dose vitamin C has recently attracted attention as a cancer therapy. High-dose induces pro-oxidant effects and selectively kills cells. However, the anticancer mechanisms are not fully understood. Here, we analyzed metabolic changes induced by in MCF7 human breast adenocarcinoma HT29 colon cells using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). The metabolomic profiles both cell lines were dramatically altered after exposure to cytotoxic concentrations C. Levels upstream metabolites glycolysis pathway tricarboxylic acid (TCA) cycle increased following treatment with C, while adenosine triphosphate (ATP) levels adenylate energy charges decreased concentration-dependently. Treatment N -acetyl cysteine (NAC) reduced glutathione (GSH) significantly inhibited C-induced cytotoxicity NAC also suppressed C-dependent NAD prevented death. Collectively, our data suggests that metabolism through depletion, thereby inducing