Electron paramagnetic resonance study of peripheral blood mononuclear cells from patients with refractory solid tumors treated with Triapine®
Electron paramagnetic resonance study of peripheral blood mononuclear cells from patients with refractory solid tumors treated with Triapine®
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DOI：
10.1016/j.jinorgbio.2007.10.013
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发表时间：
2008-04-01
影响因子：
3.9
通讯作者：
Antholine, William E.
中科院分区：
文献类型：
--
作者：
Kolesar, Jill M.;Schelman, William R.;Antholine, William E.
金属螯合剂Triapineo（3-氨基吡啶-2-羧基硫代氨基脲）是一种有效的核糖核苷酸还原酶抑制剂。在接受曲平治疗的患者外周血运动核细胞（PBMCs）中观察到与铁转铁蛋白、血红素和低自旋铁或铜离子信号一致的EPR谱（(R)）。一个被明确识别的信号是铁转铁蛋白信号。据推测，fe2或CuT产生的活性氧会破坏转铁蛋白或转铁蛋白受体，从而阻断铁的摄取。血红素信号增加的一个潜在来源是线粒体释放的细胞色素e。这些结果为Triapineo的体内作用机制提供了有价值的见解。(c) 2007爱思唯尔公司版权所有。
The metal chelator Triapineo, 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 motionuclear cells (PBMCs) obtained from patients treated with Triapine((R)). 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 e released from the mitochondria. These results provide valuable insight into the in vivo mechanism of action of Triapineo. (c) 2007 Elsevier Inc. All rights reserved.