Breast Cancer Stem Cell Potent Copper(II)-Non-Steroidal Anti-Inflammatory Drug Complexes
Breast Cancer Stem Cell Potent Copper(II)-Non-Steroidal Anti-Inflammatory Drug Complexes
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DOI：
10.1002/anie.201510443
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发表时间：
2016-02-18
影响因子：
16.6
通讯作者：
Suntharalingam, Kogularamanan
中科院分区：
文献类型：
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作者：
Boodram, Janine N.;Mcgregor, Iain J.;Suntharalingam, Kogularamanan
本文报道了一系列含非甾体抗炎药吲哚美辛的铜（II）-邻菲咯啉配合物对乳腺癌干细胞（CSC）的作用。该系列中最有效的铜（II）络合物4选择性杀死乳腺CSC富集的HMLER-shEcad细胞超过乳腺CSC耗尽的HMLER细胞。此外，4降低乳腺球的形成、大小和活力的程度大于盐霉素，盐霉素是一种已知选择性抑制CSC的钾离子载体。机制研究表明，观察到的4 CSC特异性源于其产生细胞内活性氧（ROS）和抑制环加氧酶-2（考克斯-2）的能力，环加氧酶-2是一种在乳腺CSC中过表达的酶。前者诱导DNA损伤，激活JNK和p38通路，并导致细胞凋亡。乳腺癌复发与乳腺癌患者的
The breast cancer stem cell (CSC) potency of a series of copper(II)-phenanthroline complexes containing the nonsteroidal anti-inflammatory drug (NSAID), indomethacin, is reported. The most effective copper(II) complex in this series, 4, selectivity kills breast CSC-enriched HMLER-shEcad cells over breast CSC-depleted HMLER cells. Furthermore, 4 reduces the formation, size, and viability of mammospheres, to a greater extent than salinomycin, a potassium ionophore known to selectively inhibit CSCs. Mechanistic studies revealed that the CSC-specificity observed for 4 arises from its ability to generate intracellular reactive oxygen species (ROS) and inhibit cyclooxygenase-2 (COX-2), an enzyme that is overexpressed in breast CSCs. The former induces DNA damage, activates JNK and p38 pathways, and leads to apoptosis. Breast cancer recurrence is strongly linked to the existence