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®.
|Number of pages||6|
|Journal||Journal of Inorganic Biochemistry|
|State||Published - Apr 2008|
Bibliographical noteFunding 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.
- 3-aminopyridine-2-carboxaldehyde thiosemicarbazone
- Electron paramagnetic resonance (EPR)
- Patients with solid tumors
- Peripheral blood mononuclear cells (PBMCs)
- Reactive oxygen species (ROS)
- Ribonucleotide reductase
- Transferrin receptor
ASJC Scopus subject areas
- Inorganic Chemistry