Electron paramagnetic resonance study of peripheral blood mononuclear cells from patients with refractory solid tumors treated with Triapine®

Jill M. Kolesar, William R. Schelman, Peter G. Geiger, Kyle D. Holen, Anne M. Traynor, Dona B. Alberti, James P. Thomas, Christopher R. Chitambar, George Wilding, William E. Antholine

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

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 languageEnglish
Pages (from-to)693-698
Number of pages6
JournalJournal of Inorganic Biochemistry
Volume102
Issue number4
DOIs
StatePublished - 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

Fingerprint

Dive into the research topics of 'Electron paramagnetic resonance study of peripheral blood mononuclear cells from patients with refractory solid tumors treated with Triapine®'. Together they form a unique fingerprint.

Cite this