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The discrete breast cancer stem cell mammosphere activity of Group 10-bis(azadiphosphine) metal complexes.

journal contribution
posted on 15.01.2021, 08:56 by Zhiyin Xiao, Alice Johnson, Kuldip Singh, Kogularamanan Suntharalingam
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.

History

Author affiliation

Department of Chemistry

Version

AM (Accepted Manuscript)

Published in

Angewandte Chemie (International ed. in English)

Publisher

Wiley

issn

1433-7851

eissn

1521-3773

Acceptance date

02/12/2020

Copyright date

2020

Available date

03/12/2021

Spatial coverage

Germany

Language

eng