Electron paramagnetic resonance study of peripheral blood mononuclear cells from patients with refractory solid tumors treated with Triapine.
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 FeT(2) 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.
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center, University of Wisconsin-Madison, 600 Highland Avenue, Room K4/554, Madison, WI 53792, USA. jmkolesar@pharmacy.wisc.edu
Jill M
JM
Kolesar
William R
WR
Schelman
Peter G
PG
Geiger
Kyle D
KD
Holen
Anne M
AM
Traynor
Dona B
DB
Alberti
James P
JP
Thomas
Christopher R
CR
Chitambar
George
G
Wilding
William E
WE
Antholine
D045304:Cytochromes c / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D009000:Monocytes / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy*; D011725:Pyridines / Q000627:therapeutic use*; D013882:Thiosemicarbazones / Q000627:therapeutic use*
D011725:Pyridines; D013882:Thiosemicarbazones; C078157:3-aminopyridine-2-carboxaldehyde thiosemicarbazone; D045304:Cytochromes c