期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 60, 期 12, 页码 6704-6709出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202014242
关键词
antitumour agents; cancer stem cells; DNA damage; Group 10; mammosphere
资金
- EPSRC New Investigator Award [EP/S005544/1]
- National Natural Science Foundation of China [21807047]
- EPSRC [EP/S005544/1] Funding Source: UKRI
A series of Group 10-bis(azadiphosphine) complexes 1-3 demonstrated anti-breast cancer stem cell properties, with the platinum complex 3 being the most effective compared to other complexes and known CSC-active compounds. Mechanistic studies showed that the complexes could penetrate CSC mammospheres, induce DNA damage, and trigger apoptosis.
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.
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