High dose vitamin C in metastatic lung cancer and glioblastoma multiforme:
High dose vitamin C in metastatic lung cancer and glioblastoma multiforme:
Highlights
- High-dose ascorbate sensitizes NSCLC and GBM cells to radio-chemotherapy
- O2⋅− and H2O2 increase labile iron causing cancer cell-selective ascorbate toxicity
- Therapeutic levels of ascorbate are achievable and well tolerated in GBM and NSCLC
- Cancer cell oxidative metabolism can be targeted with ascorbate for cancer therapy
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.
Graphical Abstract
