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

doi:10.1016/j.jinorgbio.2007.10.013

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 journal › Article › peer-review

28 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 language	English
Pages (from-to)	693-698
Number of pages	6
Journal	Journal of Inorganic Biochemistry
Volume	102
Issue number	4
DOIs	https://doi.org/10.1016/j.jinorgbio.2007.10.013
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

Access to Document

10.1016/j.jinorgbio.2007.10.013

Cite this

Kolesar, J. M., Schelman, W. R., Geiger, P. G., Holen, K. D., Traynor, A. M., Alberti, D. B., Thomas, J. P., Chitambar, C. R., Wilding, G., & Antholine, W. E. (2008). Electron paramagnetic resonance study of peripheral blood mononuclear cells from patients with refractory solid tumors treated with Triapine^®. Journal of Inorganic Biochemistry, 102(4), 693-698. https://doi.org/10.1016/j.jinorgbio.2007.10.013

@article{4b7b377b2a0e4c758749a6105ecb36e0,

title = "Electron paramagnetic resonance study of peripheral blood mononuclear cells from patients with refractory solid tumors treated with Triapine{\textregistered}",

abstract = "The metal chelator Triapine{\textregistered}, 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{\textregistered}. 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{\textregistered}.",

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",

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

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.",

year = "2008",

month = apr,

doi = "10.1016/j.jinorgbio.2007.10.013",

language = "English",

volume = "102",

pages = "693--698",

number = "4",

}

Kolesar, JM, Schelman, WR, Geiger, PG, Holen, KD, Traynor, AM, Alberti, DB, Thomas, JP, Chitambar, CR, Wilding, G & Antholine, WE 2008, 'Electron paramagnetic resonance study of peripheral blood mononuclear cells from patients with refractory solid tumors treated with Triapine^®', Journal of Inorganic Biochemistry, vol. 102, no. 4, pp. 693-698. https://doi.org/10.1016/j.jinorgbio.2007.10.013

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T1 - Electron paramagnetic resonance study of peripheral blood mononuclear cells from patients with refractory solid tumors treated with Triapine®

AU - Kolesar, Jill M.

AU - Schelman, William R.

AU - Geiger, Peter G.

AU - Holen, Kyle D.

AU - Traynor, Anne M.

AU - Alberti, Dona B.

AU - Thomas, James P.

AU - Chitambar, Christopher R.

AU - Wilding, George

AU - Antholine, William E.

N1 - 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.

PY - 2008/4

Y1 - 2008/4

N2 - 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®.

AB - 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®.

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KW - Peripheral blood mononuclear cells (PBMCs)

KW - Reactive oxygen species (ROS)

KW - Ribonucleotide reductase

KW - Transferrin

KW - Transferrin receptor

KW - Triapine

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