Disulfide-masked iron prochelators: Effects on cell death, proliferation, and hemoglobin production.
Disulfide-masked iron prochelators: Effects on cell death, proliferation, and hemoglobin production.
复制标题
DOI：
10.1016/j.jinorgbio.2017.12.016
复制
发表时间：
2018-03
影响因子：
3.9
通讯作者：
Tomat E
中科院分区：
文献类型：
--
作者：
Akam EA;Utterback RD;Marcero JR;Dailey HA;Tomat E
恶性细胞的铁代谢被改变以确保更高的获取和利用率，这推动了癌症治疗中铁螯合策略的研究。在旨在提高细胞内特异性的预螯合方法中，二硫键还原/激活开关被整合到铁结合支架上，从而产生细胞内激活的清除剂。在此，该策略应用于几种三齿供体组，包括缩氨基硫脲、芳酰腙和缩氨基脲。新型前螯合剂系统在乳腺癌细胞系（MCF-7 和转移性 MDA-MB-231）中具有抗增殖作用，并且不会导致细胞内氧化应激的产生。与缺铁一致，所测试的前螯合剂导致细胞周期在 G1/S 界面停滞并诱导细胞凋亡。值得注意的是，尽管人体中合成血红蛋白的血细胞对铁的需求量最高，但在分化红系细胞的 MEL（小鼠红白血病）模型中未观察到对血红蛋白产生的显着影响。这项研究提供了有关二硫键预螯合剂细胞内效应的新信息，并表明芳酰腙 (AH1-S)2 是一类新型抗增殖预螯合剂系统的有前途的原型。
The iron metabolism of malignant cells, which is altered to ensure higher acquisition and utilization, motivates the investigation of iron chelation strategies in cancer treatment. In a prochelation approach aimed at increasing intracellular specificity, disulfide reduction/activation switches are incorporated on iron-binding scaffolds resulting in intracellularly activated scavengers. Herein, this strategy is applied to several tridentate donor sets including thiosemicarbazones, aroylhydrazones and semicarbazones. The novel prochelator systems are antiproliferative in breast adenocarcinoma cell lines (MCF-7 and metastatic MDA-MB-231) and do not result in the intracellular generation of oxidative stress. Consistent with iron deprivation, the tested prochelators lead to cell-cycle arrest at the G1/S interface and induction of apoptosis. Notably, although hemoglobin-synthesizing blood cells have the highest iron need in the human body, no significant impact on hemoglobin production was observed in the MEL (murine erythroleukemia) model of differentiating erythroid cells. This study provides new information on the intracellular effects of disulfide-based prochelators and indicates aroylhydrazone (AH1-S)2 as a promising prototype of a new class of antiproliferative prochelator systems.
登录
查看更多内容
影响因子：
15
作者：
Aron AT;Loehr MO;Bogena J;Chang CJ
通讯作者：
Chang CJ
DOI：
10.1016/0006-291x(79)91133-1
发表时间：
1979-01-01
影响因子：
3.1
作者：
EBERT, PS;HESS, RA;TSCHUDY, DP
通讯作者：
TSCHUDY, DP
影响因子：
15
作者：
Charkoudian, Louise K.;Pham, David M.;Franz, Katherine J.
通讯作者：
Franz, Katherine J.
影响因子：
4.8
作者：
Jansson, Patric J.;Yamagishi, Tetsuo;Richardson, Des R.
通讯作者：
Richardson, Des R.
DOI：
10.1016/j.bbamcr.2016.09.008
发表时间：
2016-12-01
影响因子：
5.1
作者：
Hamdi, Arnel;Roshan, Tariq M.;Ponka, Prem
通讯作者：
Ponka, Prem