用曲磷胺治疗的难治性实体瘤患者外周血单个核细胞的电子顺磁共振研究
Electron paramagnetic resonance study of peripheral blood mononuclear cells from patients with refractory solid tumors treated with Triapine.
作者信息
Kolesar Jill M, Schelman William R, Geiger Peter G, Holen Kyle D, Traynor Anne M, Alberti Dona B, Thomas James P, Chitambar Christopher R, Wilding George, Antholine William E
机构信息
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center, University of Wisconsin-Madison, 600 Highland Avenue, Room K4/554, Madison, WI 53792, USA.
出版信息
J Inorg Biochem. 2008 Apr;102(4):693-8. doi: 10.1016/j.jinorgbio.2007.10.013. Epub 2007 Oct 30.
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 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.
摘要
金属螯合剂曲拉派定（3-氨基吡啶-2-羧醛缩氨基硫脲）是核糖核苷酸还原酶的有效抑制剂。在用曲拉派定治疗的患者外周血单个核细胞（PBMC）中观察到与铁转铁蛋白、血红素以及低自旋铁或铜离子信号一致的电子顺磁共振（EPR）光谱。一个明确鉴定出的信号是铁转铁蛋白的信号。据推测，铁摄取被FeT(2)或CuT产生的活性氧所阻断，这些活性氧会损伤转铁蛋白或转铁蛋白受体。血红素信号增加的一个潜在来源是从线粒体释放的细胞色素c。这些结果为曲拉派定的体内作用机制提供了有价值的见解。
相似文献
1
Electron paramagnetic resonance study of peripheral blood mononuclear cells from patients with refractory solid tumors treated with Triapine.
J Inorg Biochem. 2008 Apr;102(4):693-8. doi: 10.1016/j.jinorgbio.2007.10.013. Epub 2007 Oct 30.
2
Cytotoxic Evaluation of 3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone, 3-AP, in Peripheral Blood Lymphocytes of Patients with Refractory Solid Tumors using Electron Paramagnetic Resonance.
Exp Ther Med. 2011 Jan;2(1):119-123. doi: 10.3892/etm.2010.165.
3
Concentration of Fe(3+)-Triapine in BEAS-2B Cells.
Int J Mol Sci. 2019 Jun 22;20(12):3062. doi: 10.3390/ijms20123062.
4
A Ferrous-Triapine complex mediates formation of reactive oxygen species that inactivate human ribonucleotide reductase.
Mol Cancer Ther. 2006 Mar;5(3):586-92. doi: 10.1158/1535-7163.MCT-05-0384.
5
Triapine (3-aminopyridine-2-carboxaldehyde- thiosemicarbazone): A potent inhibitor of ribonucleotide reductase activity with broad spectrum antitumor activity.
Biochem Pharmacol. 2000 Apr 15;59(8):983-91. doi: 10.1016/s0006-2952(99)00419-0.
6
7
Ribonucleotide reductase inhibition by metal complexes of Triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone): a combined experimental and theoretical study.
J Inorg Biochem. 2011 Nov;105(11):1422-31. doi: 10.1016/j.jinorgbio.2011.07.003. Epub 2011 Jul 31.
8
In vitro and in vivo radiosensitization induced by the ribonucleotide reductase inhibitor Triapine (3-aminopyridine-2-carboxaldehyde-thiosemicarbazone).
Clin Cancer Res. 2006 May 1;12(9):2912-8. doi: 10.1158/1078-0432.CCR-05-2860.
9
Impact of metal coordination on cytotoxicity of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (triapine) and novel insights into terminal dimethylation.
J Med Chem. 2009 Aug 27;52(16):5032-43. doi: 10.1021/jm900528d.
10
Mechanistic studies of semicarbazone triapine targeting human ribonucleotide reductase in vitro and in mammalian cells: tyrosyl radical quenching not involving reactive oxygen species.
J Biol Chem. 2012 Oct 12;287(42):35768-35778. doi: 10.1074/jbc.M112.396911. Epub 2012 Aug 22.
引用本文的文献
1
Transient Adaptation of to Exposure by Thiosemicarbazone Drugs That Target Ribosomal Proteins Is Associated with the Upregulated Expression of Tachyzoite Transmembrane Proteins and Transporters.
Int J Mol Sci. 2024 Aug 21;25(16):9067. doi: 10.3390/ijms25169067.
2
Harnessing microbial iron chelators to develop innovative therapeutic agents.
J Adv Res. 2022 Jul;39:89-101. doi: 10.1016/j.jare.2021.10.010. Epub 2021 Nov 1.
3
Activity and electrochemical properties: iron complexes of the anticancer drug triapine and its analogs.
J Biol Inorg Chem. 2019 Aug;24(5):621-632. doi: 10.1007/s00775-019-01675-0. Epub 2019 Jun 27.
4
Redox activation of Fe(III)-thiosemicarbazones and Fe(III)-bleomycin by thioredoxin reductase: specificity of enzymatic redox centers and analysis of reactive species formation by ESR spin trapping.
Free Radic Biol Med. 2013 Jul;60:183-94. doi: 10.1016/j.freeradbiomed.2013.02.016. Epub 2013 Feb 26.
5
Mechanistic studies of semicarbazone triapine targeting human ribonucleotide reductase in vitro and in mammalian cells: tyrosyl radical quenching not involving reactive oxygen species.
J Biol Chem. 2012 Oct 12;287(42):35768-35778. doi: 10.1074/jbc.M112.396911. Epub 2012 Aug 22.
6
Iron-targeting antitumor activity of gallium compounds and novel insights into triapine(®)-metal complexes.
Antioxid Redox Signal. 2013 Mar 10;18(8):956-72. doi: 10.1089/ars.2012.4880. Epub 2012 Oct 3.
7
EPR Study of Iron Ion Complexes in Human Blood.
Appl Magn Reson. 2011 May;40(3):321-330. doi: 10.1007/s00723-011-0219-3. Epub 2011 Apr 5.
8
Cytotoxic Evaluation of 3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone, 3-AP, in Peripheral Blood Lymphocytes of Patients with Refractory Solid Tumors using Electron Paramagnetic Resonance.
Exp Ther Med. 2011 Jan;2(1):119-123. doi: 10.3892/etm.2010.165.
9
Population pharmacokinetics of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (Triapine®) in cancer patients.
Cancer Chemother Pharmacol. 2011 Feb;67(2):393-400. doi: 10.1007/s00280-010-1331-z. Epub 2010 May 4.
本文引用的文献
1
Chelators at the cancer coalface: desferrioxamine to Triapine and beyond.
Clin Cancer Res. 2006 Dec 1;12(23):6876-83. doi: 10.1158/1078-0432.CCR-06-1954.
2
Dipyridyl thiosemicarbazone chelators with potent and selective antitumor activity form iron complexes with redox activity.
J Med Chem. 2006 Nov 2;49(22):6510-21. doi: 10.1021/jm0606342.
3
A class of iron chelators with a wide spectrum of potent antitumor activity that overcomes resistance to chemotherapeutics.
Proc Natl Acad Sci U S A. 2006 Oct 3;103(40):14901-6. doi: 10.1073/pnas.0604979103. Epub 2006 Sep 26.
4
A Ferrous-Triapine complex mediates formation of reactive oxygen species that inactivate human ribonucleotide reductase.
Mol Cancer Ther. 2006 Mar;5(3):586-92. doi: 10.1158/1535-7163.MCT-05-0384.
5
Triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone) induces apoptosis in ovarian cancer cells.
J Soc Gynecol Investig. 2006 Feb;13(2):145-52. doi: 10.1016/j.jsgi.2005.11.004.
6
7
Cytochrome c release from mitochondria: all or nothing.
Nat Cell Biol. 2000 Mar;2(3):E41-3. doi: 10.1038/35004069.
8
The relationship of intracellular iron chelation to the inhibition and regeneration of human ribonucleotide reductase.
J Biol Chem. 1996 Aug 23;271(34):20291-9. doi: 10.1074/jbc.271.34.20291.
9
Interaction of 2-formylpyridine thiosemicarbazonato copper (II) with Ehrlich ascites tumor cells.
Biochem Pharmacol. 1981 Jun 15;30(12):1595-604. doi: 10.1016/0006-2952(81)90386-5.
10
Effect of chelating agents upon the synthesis of nucleic acids and protein: inhibition of DNA synthesis by 1-formylisoquinoline thiosemicarbazone.
Biochem Biophys Res Commun. 1967 Apr 7;27(1):26-32. doi: 10.1016/s0006-291x(67)80034-2.
Zotero 插件