期刊
CANCER CELL
卷 31, 期 4, 页码 487-+出版社
CELL PRESS
DOI: 10.1016/j.ccell.2017.02.018
关键词
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资金
- Carver College of Medicine, Holden Comprehensive Cancer Center
- Iowa City Veteran's Administration Medical Center
- American Society for Radiation Oncology (ASTRO) [JF2014-1]
- Carver Research Program of Excellence in Redox Biology
- US NIH [R01-CA182804, R01-CA184051, R01-CA169046, U01-CA166800]
- [CCSG P30-CA086862]
- [T32-GM007337]
- [T32-CA078586]
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 O-2(center dot-) 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.
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