The Discrete Breast Cancer Stem Cell Mammosphere Activity of Group 10-Bis(azadiphosphine) Metal Complexes
Dr. Zhiyin Xiao
School of Chemistry, University of Leicester, Leicester, UK
College of Biological, Chemical Sciences and Engineering, Jiaxing University, Jiaxing, China
These authors contributed equally to this work.
Search for more papers by this authorDr. Alice Johnson
School of Chemistry, University of Leicester, Leicester, UK
These authors contributed equally to this work.
Search for more papers by this authorDr. Kuldip Singh
School of Chemistry, University of Leicester, Leicester, UK
Search for more papers by this authorCorresponding Author
Dr. Kogularamanan Suntharalingam
School of Chemistry, University of Leicester, Leicester, UK
Search for more papers by this authorDr. Zhiyin Xiao
School of Chemistry, University of Leicester, Leicester, UK
College of Biological, Chemical Sciences and Engineering, Jiaxing University, Jiaxing, China
These authors contributed equally to this work.
Search for more papers by this authorDr. Alice Johnson
School of Chemistry, University of Leicester, Leicester, UK
These authors contributed equally to this work.
Search for more papers by this authorDr. Kuldip Singh
School of Chemistry, University of Leicester, Leicester, UK
Search for more papers by this authorCorresponding Author
Dr. Kogularamanan Suntharalingam
School of Chemistry, University of Leicester, Leicester, UK
Search for more papers by this authorAbstract
We report the anti-breast cancer stem cell (CSC) properties of a series of Group 10-bis(azadiphosphine) complexes 1–3 under exclusively three-dimensional cell culture conditions. The breast CSC mammosphere potency of 1–3 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.
Conflict of interest
The authors declare no conflict of interest.
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