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The Discrete Breast Cancer Stem Cell Mammosphere Activity of Group 10‐Bis(azadiphosphine) Metal Complexes
Author(s) -
Xiao Zhiyin,
Johnson Alice,
Singh Kuldip,
Suntharalingam Kogularamanan
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202014242
Subject(s) - chemistry , apoptosis , cancer research , breast cancer , potency , stereochemistry , cancer stem cell , metal , cancer , stem cell , medicine , biology , microbiology and biotechnology , biochemistry , in vitro , organic chemistry
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.