Extracellular iron diminishes anticancer effects of vitamin C: An in vitro study
2014
Authors:
Mojić, MarijaBogdanović Pristov, Jelena
Maksimović-Ivanić, Danijela
Jones, David R.
Stanic, Marina
Mijatović, Sanja
Spasojevic, Ivan
Document Type:
Article (Published version)
Metadata
Show full item recordAbstract:
In vitro studies have shown that hydrogen peroxide (H2O2) produced by
high-concentration ascorbate and cell culture medium iron efficiently
kills cancer cells. This provided the rationale for clinical trials of
high-dose intravenous ascorbate-based treatment for cancer. A drawback
in all the in vitro studies was their failure to take into account the
in vivo concentration of iron to supplement cell culture media which are
characterized by low iron content. Here we showed, using two prostate
cancer cell lines (LNCaP and PC-3) and primary astrocytes, that the
anticancer/cytotoxic effects of ascorbate are completely abolished by
iron at physiological concentrations in cell culture medium and human
plasma. A detailed examination of mechanisms showed that iron at
physiological concentrations promotes both production and decomposition
of H2O2. The latter is mediated by Fenton reaction and prevents H2O2
accumulation. The hydroxyl radical, which is produced in the Fenton
reaction, is buffered by extracellular proteins, and could not affect
intracellular targets like H2O2. These findings show that anticancer
effects of ascorbate have been significantly overestimated in previous
in vitro studies, and that common cell culture media might be unsuitable
for redox research.
Source:
Scientific Reports, 2014, 4, 5955Funding / projects:
- Molecular mechanisms of physiological and pharmacological control of inflammation and cancer (RS-MESTD-Basic Research (BR or ON)-173013)
- Molecular mechanisms of redox signalling in homeostasis: adaptation and pathology (RS-MESTD-Basic Research (BR or ON)-173014)
DOI: 10.1038/srep05955
ISSN: 2045-2322