| Literature DB >> 28366679 |
Joshua D Schoenfeld1, Zita A Sibenaller1, Kranti A Mapuskar1, Brett A Wagner1, Kimberly L Cramer-Morales1, Muhammad Furqan2, Sonia Sandhu2, Thomas L Carlisle2, Mark C Smith1, Taher Abu Hejleh2, Daniel J Berg2, Jun Zhang2, John Keech3, Kalpaj R Parekh3, Sudershan Bhatia1, Varun Monga2, Kellie L Bodeker1, Logan Ahmann1, Sandy Vollstedt1, Heather Brown1, Erin P Shanahan Kauffman2, Mary E Schall2, Ray J Hohl2, Gerald H Clamon2, Jeremy D Greenlee4, Matthew A Howard4, Michael K Schultz5, Brian J Smith6, Dennis P Riley7, Frederick E Domann1, Joseph J Cullen3, Garry R Buettner1, John M Buatti1, Douglas R Spitz8, Bryan G Allen9.
Abstract
Pharmacological ascorbate has been proposed as a potential anti-cancer agent when combined with radiation and chemotherapy. The anti-cancer effects of ascorbate are hypothesized to involve the autoxidation of ascorbate leading to increased steady-state levels of H2O2; however, the mechanism(s) for cancer cell-selective toxicity remain unknown. The current study shows that alterations in cancer cell mitochondrial oxidative metabolism resulting in increased levels of O2⋅- and H2O2 are capable of disrupting intracellular iron metabolism, thereby selectively sensitizing non-small-cell lung cancer (NSCLC) and glioblastoma (GBM) cells to ascorbate through pro-oxidant chemistry involving redox-active labile iron and H2O2. In addition, preclinical studies and clinical trials demonstrate the feasibility, selective toxicity, tolerability, and potential efficacy of pharmacological ascorbate in GBM and NSCLC therapy.Entities:
Keywords: ferritin; glioblastoma multiforme; hydrogen peroxide; labile iron metabolism; non-small cell lung cancer; oxidative stress; pharmacological ascorbate; superoxide; superoxide dismutase; transferrin receptor
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Year: 2017 PMID： 28366679 PMCID： PMC5497844 DOI： 10.1016/j.ccell.2017.02.018
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743