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Article

Cytotoxic evaluation of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone in peripheral blood lymphocytes of patients with refractory solid tumors using electron paramagnetic resonance

  • Authors:
    • Jill M. Kolesar
    • Kamakshi Sachidanandam
    • William R. Schelman
    • Jens Eickhoff
    • Kyle D. Holen
    • Anne M. Traynor
    • Dona B. Alberti
    • James P. Thomas
    • Christopher R. Chitambar
    • George Wilding
    • William E. Antholine
  • View Affiliations / Copyright

    Affiliations: University of Wisconsin Paul P. Carbone Comprehensive Cancer Center, University of Wisconsin-Madison, Madison, WI 53792-5669, USA, University of Wisconsin Paul P. Carbone Comprehensive Cancer Center, University of Wisconsin-Madison, Madison, WI 53792-5669, USA, Department of Biostatistics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA, Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI 53226, USA
  • Pages: 119-123
    |
    Published online on: November 30, 2010
       https://doi.org/10.3892/etm.2010.165
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Abstract

3-Aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) is a metal chelator that potently inhibits the enzyme ribonucleotide reductase (RR), which plays a key role in cell division and tumor progression. A subunit of RR has a non-heme iron and a tyrosine-free radical, which are required for the enzymatic reduction of ribonucleotides to deoxyribonucleotides. The objective of the present study was to determine whether 3-AP affects its targeted action by measuring electron paramagnetic resonance (EPR) signals formed either directly or indirectly from low molecular weight ferric-3-AP chelates. Peripheral blood lymphocytes were collected from patients with refractory solid tumors at baseline and at 2, 4.5 and 22 h after 3-AP administration. Using EPR spectra, our study identified signals from high-spin Fe-transferrin, high-spin heme and low-spin iron or copper ions. An increase in the Fe-transferrin signal was observed, suggesting blockage of Fe uptake. It is hypothesized that formation of reactive oxygen species by FeT2 or CuT damages the transferrin or the transferrin receptor. An increase in the heme signal was also observed, which was a probable source of cytochrome c release from the mitochondria and potential apoptosis. In addition, increased levels of Fe and Cu were identified. These results, which were consistent with our previous study validating 3-AP-mediated signals by EPR, provide valuable insights into the in vivo mechanism of action of 3-AP.
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Copy and paste a formatted citation
Spandidos Publications style
Kolesar JM, Sachidanandam K, Schelman WR, Eickhoff J, Holen KD, Traynor AM, Alberti DB, Thomas JP, Chitambar CR, Wilding G, Wilding G, et al: Cytotoxic evaluation of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone in peripheral blood lymphocytes of patients with refractory solid tumors using electron paramagnetic resonance. Exp Ther Med 2: 119-123, 2011.
APA
Kolesar, J.M., Sachidanandam, K., Schelman, W.R., Eickhoff, J., Holen, K.D., Traynor, A.M. ... Antholine, W.E. (2011). Cytotoxic evaluation of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone in peripheral blood lymphocytes of patients with refractory solid tumors using electron paramagnetic resonance. Experimental and Therapeutic Medicine, 2, 119-123. https://doi.org/10.3892/etm.2010.165
MLA
Kolesar, J. M., Sachidanandam, K., Schelman, W. R., Eickhoff, J., Holen, K. D., Traynor, A. M., Alberti, D. B., Thomas, J. P., Chitambar, C. R., Wilding, G., Antholine, W. E."Cytotoxic evaluation of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone in peripheral blood lymphocytes of patients with refractory solid tumors using electron paramagnetic resonance". Experimental and Therapeutic Medicine 2.1 (2011): 119-123.
Chicago
Kolesar, J. M., Sachidanandam, K., Schelman, W. R., Eickhoff, J., Holen, K. D., Traynor, A. M., Alberti, D. B., Thomas, J. P., Chitambar, C. R., Wilding, G., Antholine, W. E."Cytotoxic evaluation of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone in peripheral blood lymphocytes of patients with refractory solid tumors using electron paramagnetic resonance". Experimental and Therapeutic Medicine 2, no. 1 (2011): 119-123. https://doi.org/10.3892/etm.2010.165
Copy and paste a formatted citation
x
Spandidos Publications style
Kolesar JM, Sachidanandam K, Schelman WR, Eickhoff J, Holen KD, Traynor AM, Alberti DB, Thomas JP, Chitambar CR, Wilding G, Wilding G, et al: Cytotoxic evaluation of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone in peripheral blood lymphocytes of patients with refractory solid tumors using electron paramagnetic resonance. Exp Ther Med 2: 119-123, 2011.
APA
Kolesar, J.M., Sachidanandam, K., Schelman, W.R., Eickhoff, J., Holen, K.D., Traynor, A.M. ... Antholine, W.E. (2011). Cytotoxic evaluation of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone in peripheral blood lymphocytes of patients with refractory solid tumors using electron paramagnetic resonance. Experimental and Therapeutic Medicine, 2, 119-123. https://doi.org/10.3892/etm.2010.165
MLA
Kolesar, J. M., Sachidanandam, K., Schelman, W. R., Eickhoff, J., Holen, K. D., Traynor, A. M., Alberti, D. B., Thomas, J. P., Chitambar, C. R., Wilding, G., Antholine, W. E."Cytotoxic evaluation of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone in peripheral blood lymphocytes of patients with refractory solid tumors using electron paramagnetic resonance". Experimental and Therapeutic Medicine 2.1 (2011): 119-123.
Chicago
Kolesar, J. M., Sachidanandam, K., Schelman, W. R., Eickhoff, J., Holen, K. D., Traynor, A. M., Alberti, D. B., Thomas, J. P., Chitambar, C. R., Wilding, G., Antholine, W. E."Cytotoxic evaluation of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone in peripheral blood lymphocytes of patients with refractory solid tumors using electron paramagnetic resonance". Experimental and Therapeutic Medicine 2, no. 1 (2011): 119-123. https://doi.org/10.3892/etm.2010.165
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