The discrete breast cancer stem cell mammosphere activity of group 10-Bis(azadiphosphine) metal complexes

XIAO, Z., JOHNSON, Alice, SINGH, K. and SUNTHARALINGAM, K. (2021). The discrete breast cancer stem cell mammosphere activity of group 10-Bis(azadiphosphine) metal complexes. Angewandte Chemie - International Edition, 60 (12), 6704-6709.

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Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	antitumour agents; cancer stem cells; DNA damage; Group 10; mammosphere; DNA damage; Group 10; antitumour agents; cancer stem cells; mammosphere; Antineoplastic Agents; Aza Compounds; Breast Neoplasms; Coordination Complexes; DNA Damage; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Molecular Structure; Neoplastic Stem Cells; Particle Size; Phosphines; Structure-Activity Relationship; Tumor Cells, Cultured; Tumor Cells, Cultured; Humans; Breast Neoplasms; DNA Damage; Phosphines; Aza Compounds; Antineoplastic Agents; Drug Screening Assays, Antitumor; Molecular Structure; Structure-Activity Relationship; Dose-Response Relationship, Drug; Particle Size; Neoplastic Stem Cells; Coordination Complexes; Organic Chemistry; 03 Chemical Sciences
Identification Number:	https://doi.org/10.1002/anie.202014242
Page Range:	6704-6709
SWORD Depositor:	Symplectic Elements
Depositing User:	Symplectic Elements
Date Deposited:	31 Mar 2022 11:20
Last Modified:	31 Mar 2022 11:20
URI:	https://shura.shu.ac.uk/id/eprint/30017

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