The Anti-Breast Cancer Stem Cell Potency of Copper(I)-Non-Steroidal Anti-Inflammatory Drug Complexes.
The Anti-Breast Cancer Stem Cell Potency of Copper(I)-Non-Steroidal Anti-Inflammatory Drug Complexes.
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DOI：
10.3390/molecules28176401
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发表时间：
2023-09-01
期刊：
影响因子：
4.6
通讯作者：
Suntharalingam, Kogularamanan
中科院分区：
文献类型：
--
作者：
Johnson, Alice;Feng, Xiao;Singh, Kuldip;Ortu, Fabrizio;Suntharalingam, Kogularamanan
关键词：
癌症干细胞（CSC）被认为是转移和癌症复发的部分原因。目前，没有有效的治疗选择可以以临床安全剂量去除CSC。在这里，我们报告了一系列铜（I）配合物的合成，表征和抗乳腺癌CSC性能，包括非甾体抗炎药（NSAID）和三苯基膦配体（1-3）。铜（I）络合物能够以微摩尔浓度降低在二维和三维培养物中生长的乳腺CSC的活力。铜（I）络合物对乳腺CSC的效力与盐霉素（一种已建立的抗乳腺CSC剂）和顺铂（一种临床使用的金属药物）相似。基于细胞的研究表明，铜（I）络合物容易且类似地被乳腺CSC内化。铜（I）络合物显著增加乳腺CSC中的细胞内活性氧（ROS）水平，并且它们相对于时间的ROS生成曲线取决于存在的NSAID组分。铜（I）络合物产生的细胞内ROS可能是其引起乳腺CSC死亡的潜在机制的一部分。据我们所知，这是第一项探索铜（I）配合物抗乳腺癌CSC特性的研究。
Cancer stem cells (CSCs) are thought to be partly responsible for metastasis and cancer relapse. Currently, there are no effective therapeutic options that can remove CSCs at clinically safe doses. Here, we report the synthesis, characterisation, and anti-breast CSC properties of a series of copper(I) complexes, comprising of non-steroidal anti-inflammatory drugs (NSAIDs) and triphenylphosphine ligands (1–3). The copper(I) complexes are able to reduce the viability of breast CSCs grown in two- and three-dimensional cultures at micromolar concentrations. The potency of the copper(I) complexes towards breast CSCs was similar to salinomycin (an established anti-breast CSC agent) and cisplatin (a clinically used metallopharmaceutical). Cell-based studies showed that the copper(I) complexes are readily, and similarly, internalised by breast CSCs. The copper(I) complexes significantly increase the intracellular reactive oxygen species (ROS) levels in breast CSCs, and their ROS generation profile with respect to time is dependent on the NSAID component present. The generation of intracellular ROS by the copper(I) complexes could be part of the underlying mechanism by which they evoke breast CSC death. As far as we are aware, this is the first study to explore the anti-breast CSC properties of copper(I) complexes.
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影响因子：
10.5
作者：
Dontu, G;Abdallah, WM;Wicha, MS
通讯作者：
Wicha, MS
影响因子：
2.8
作者：
DARENSBOURG, DJ;HOLTCAMP, MW;REIBENSPIES, JH
通讯作者：
REIBENSPIES, JH
影响因子：
16.6
作者：
Boodram, Janine N.;Mcgregor, Iain J.;Suntharalingam, Kogularamanan
通讯作者：
Suntharalingam, Kogularamanan
影响因子：
4.6
作者：
Balakrishna, Maravanji S.;Suresh, D.;Panda, Dulal
通讯作者：
Panda, Dulal
DOI：
10.1002/cbic.202000553
发表时间：
2020-12-11
期刊：
Chembiochem : a European journal of chemical biology
影响因子：
--
作者：
Kaur P;Johnson A;Northcote-Smith J;Lu C;Suntharalingam K
通讯作者：
Suntharalingam K