Abstract
The metal chelator Triapine®, 3-aminopyridine-2-carboxaldehyde thiosemicarbazone, is a potent inhibitor of ribonucleotide reductase. EPR spectra consistent with signals from Fe-transferrin, heme, and low-spin iron or cupric ion were observed in peripheral blood mononuclear cells (PBMCs) obtained from patients treated with Triapine®. One signal that is unequivocally identified is the signal for Fe-transferrin. It is hypothesized that Fe uptake is blocked by reactive oxygen species generated by FeT2 or CuT that damage transferrin or transferrin receptor. A potential source for the increase in the heme signal is cytochrome c released from the mitochondria. These results provide valuable insight into the in vivo mechanism of action of Triapine®.
Original language | English |
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Pages (from-to) | 693-698 |
Number of pages | 6 |
Journal | Journal of Inorganic Biochemistry |
Volume | 102 |
Issue number | 4 |
DOIs | |
State | Published - Apr 2008 |
Bibliographical note
Funding Information:The EPR facilities of the Department of Biophysics at the Medical College of Wisconsin are supported by Grant EB001980 (National Biomedical EPR Center) from the National Institutes of Health.
Keywords
- 3-aminopyridine-2-carboxaldehyde thiosemicarbazone
- Electron paramagnetic resonance (EPR)
- Iron
- Patients with solid tumors
- Peripheral blood mononuclear cells (PBMCs)
- Reactive oxygen species (ROS)
- Ribonucleotide reductase
- Transferrin
- Transferrin receptor
- Triapine
ASJC Scopus subject areas
- Biochemistry
- Inorganic Chemistry