[PDF][PDF] O2⋅− and H2O2-mediated disruption of Fe metabolism causes the differential susceptibility of NSCLC and GBM cancer cells to pharmacological ascorbate

JD Schoenfeld, ZA Sibenaller, KA Mapuskar… - Cancer cell, 2017 - cell.com
JD Schoenfeld, ZA Sibenaller, KA Mapuskar, BA Wagner, KL Cramer-Morales, M Furqan
Cancer cell, 2017cell.com
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 H 2 O 2; 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⋅− and H 2 O 2 are capable of disrupting …
Summary
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.
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