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
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center, University of Wisconsin-Madison, 600 Highland Avenue, Room K4/554, Madison, WI 53792, USA.
J Inorg Biochem. 2008 Apr;102(4):693-8. doi: 10.1016/j.jinorgbio.2007.10.013. Epub 2007 Oct 30.
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.
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。
