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The Discrete Breast Cancer Stem Cell Mammosphere Activity of Group 10‐Bis(azadiphosphine) Metal Complexes
Angewandte Chemie International Edition ( IF 16.6 ) Pub Date : 2020-12-03 , DOI: 10.1002/anie.202014242
Zhiyin Xiao 1, 2 , Alice Johnson 1 , Kuldip Singh 1 , Kogularamanan Suntharalingam 1
Affiliation  

We report the anti‐breast cancer stem cell (CSC) properties of a series of Group 10‐bis(azadiphosphine) complexes 13 under exclusively three‐dimensional cell culture conditions. The breast CSC mammosphere potency of 13 is dependent on the Group 10 metal present, increasing in the following order: 1 (nickel complex) <2 (palladium complex) <3 (platinum complex). Notably, 3 reduces the formation and size of mammospheres to a greater extent than salinomycin, an established CSC‐active compound, or any reported anti‐CSC metal complex tested under similar conditions. Mechanistic studies suggest that the most effective complexes 2 and 3 readily penetrate CSC mammospheres, enter CSC nuclei, induce genomic DNA damage, and trigger caspase‐dependent apoptosis. To the best of our knowledge, this is the first study to systematically probe the anti‐CSC activity of a series of structurally related Group 10 complexes and to be conducted entirely using three‐dimensional CSC culture conditions.

中文翻译:

10-双(氮杂二膦)金属配合物的乳腺癌干细胞的离散乳球活性

我们报告一个系列第10族双(azadiphosphine)络合物的抗乳腺癌干细胞(CSC)特性1 - 3下专门三维细胞培养条件。的乳房CSC球囊效力1 - 3是依赖于第10族金属存在,按以下顺序增大:1(镍络合物)< 2(钯络合物)< 3(铂络合物)。值得注意的是,3与盐霉素,已建立的CSC活性化合物或在相似条件下测试的任何报道的抗CSC金属络合物相比,在更大程度上减少了乳球的形成和尺寸。机理研究表明,最有效的配合物23容易穿透CSC乳球,进入CSC核,诱导基因组DNA损伤,并触发caspase依赖性凋亡。据我们所知,这是第一项系统研究一系列与结构相关的第10组复合物的抗CSC活性的研究,并且将完全在三维CSC培养条件下进行。
更新日期:2020-12-03
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