%0 Journal Article
%T Anti-Migratory and Cytotoxic Activities of [Ga(8-hydroxyquinolinato)3 ]: Roles of Endogenous Cu(II) and Drug-Induced Phenotypic Changes.
%A Kuramarohit S
%A Yaourtis AM
%A Nguyen A
%A Wood ML
%A Levina A
%A Lay PA
%J Chemistry
%V 29
%N 54
%D 2023 Sep 26
%M 37385951
%F 5.02
%R 10.1002/chem.202203323
%X As shown by IncuCyte Zoom imaging proliferation assays, invasive triple-negative human breast MDA-MB-231 cancer cells treated with sub-toxic doses (5.0-20 μM, 72 h) of [GaQ3 ] (Q=8-hydroxyquinolinato) caused profound morphological changes and inhibition of cell migration, which were likely due to terminal cell differentiation or similar phenotypical change. This is the first demonstration of potential use of a metal complex in differentiation anti-cancer therapy. Additionally, a trace amount of Cu(II) (0.20 μM) added to the medium dramatically increased [GaQ3 ] cytotoxicity (IC50 ~2 μM, 72 h) due to its partial dissociation and the action of the HQ ligand as a Cu(II) ionophore, as shown with electrospray mass spectrometry and fluorescence spectroscopy assays in the medium. Hence, cytotoxicity of [GaQ3 ] is strongly linked to ligand binding of essential metal ions in the medium, for example, Cu(II). Appropriate delivery mechanisms of such complexes and their ligands could enable a powerful new triple therapeutic approach for cancer chemotherapy, including cytotoxicity against primary tumour, arrest of metastases, and activation of innate and adaptive immune responses.