Iron(III)-salophene: an organometallic compound with selective cytotoxic and anti-proliferative properties in platinum-resistant ovarian cancer cells.
Iron(III)-salophene: an organometallic compound with selective cytotoxic and anti-proliferative properties in platinum-resistant ovarian cancer cells.
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DOI：
10.1371/journal.pone.0002303
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发表时间：
2008-05-28
期刊：
影响因子：
3.7
通讯作者：
Brard L
中科院分区：
文献类型：
--
作者：
Lange TS;Kim KK;Singh RK;Strongin RM;McCourt CK;Brard L
在这项对有机金属化合物铁（III）-Saline（Fe-SP）的生物活性的先驱研究中，研究了Fe-SP对铂耐药卵巢癌细胞系的存活率、形态、增殖和细胞周期进展的具体影响。Fe-SP在100 nM至1 µM的浓度下对SKOV-3和OVCAR-3（卵巢上皮腺癌）细胞系显示出选择性细胞毒性，而HeLa细胞（宫颈上皮腺癌）或原代肺或皮肤成纤维细胞的活力不受影响。SKOV-3细胞与Fe-SP处理后的成纤维细胞相比，显示出明显的凋亡标志，包括破碎的核内染色密集的核颗粒体、高度浓缩的染色质和染色质碎片。Fe-SP处理导致细胞凋亡的外源性（Caspase-8）和内源性（Caspase-9）途径的标志物以及执行者Caspase-3的激活，而PARP-1被失活。Fe-SP作为抗增殖剂发挥作用，IC 50值为300 nM，并导致细胞通过细胞周期的S期延迟进展，导致完全S期停滞。当腹膜内应用于大鼠时，Fe-SP在初步试验中确定为大鼠卵巢癌细胞模型中化疗相关剂量的浓度下未显示出任何全身毒性。本报告表明，Fe-SP是一种有效的生长抑制剂，在体外的细胞系来源于卵巢癌和一个潜在的治疗药物，在体内治疗这种肿瘤。
In this pioneer study to the biological activity of organometallic compound Iron(III)-salophene (Fe-SP) the specific effects of Fe-SP on viability, morphology, proliferation, and cell-cycle progression on platinum-resistant ovarian cancer cell lines were investigated. Fe-SP displayed selective cytotoxicity against SKOV-3 and OVCAR-3 (ovarian epithelial adenocarcinoma) cell lines at concentrations between 100 nM and 1 µM, while the viability of HeLa cells (epithelial cervix adenocarcinoma) or primary lung or skin fibroblasts was not affected. SKOV-3 cells in contrast to fibroblasts after treatment with Fe-SP revealed apparent hallmarks of apoptosis including densely stained nuclear granular bodies within fragmented nuclei, highly condensed chromatin and chromatin fragmentation. Fe-SP treatment led to the activation of markers of the extrinsic (Caspase-8) and intrinsic (Caspase-9) pathway of apoptosis as well as of executioner Caspase-3 while PARP-1 was deactivated. Fe-SP exerted effects as an anti-proliferative agent with an IC50 value of 300 nM and caused delayed progression of cells through S-phase phase of the cell cycle resulting in a complete S-phase arrest. When intra-peritoneally applied to rats Fe-SP did not show any systemic toxicity at concentrations that in preliminary trials were determined to be chemotherapeutic relevant doses in a rat ovarian cancer cell model. The present report suggests that Fe-SP is a potent growth-suppressing agent in vitro for cell lines derived from ovarian cancer and a potential therapeutic drug to treat such tumors in vivo.
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影响因子：
7.5
作者：
EARNSHAW, WC
通讯作者：
EARNSHAW, WC
DOI：
10.1016/s0020-7292(03)90118-4
发表时间：
2003-10-01
影响因子：
3.8
作者：
Heintz, APM;Odicino, F;Pecorelli, S
通讯作者：
Pecorelli, S
影响因子：
7.3
作者：
Gust, R;Ott, I;Sommer, K
通讯作者：
Sommer, K
DOI：
10.1111/j.1048-891x.2004.014507.x
发表时间：
2004-09-01
影响因子：
4.8
作者：
Lambert, HE;Gregory, WM;Rustin, GJS
通讯作者：
Rustin, GJS
影响因子：
7.3
作者：
Doctrow, SR;Huffman, K;Malfroyt, B
通讯作者：
Malfroyt, B