A Comparison of In Vitro Studies between Cobalt(III) and Copper(II) Complexes with Thiosemicarbazone Ligands to Treat Triple Negative Breast Cancer.

Metal complexes have gained significant attention as potential anti-cancer agents. The anti-cancer activity of [Co(phen) 2 (MeATSC)](NO 3 ) 3 •1.5H 2 O•C 2 H 5 OH 1 (where phen = 1,10-phenanthroline and MeATSC = 9-anthraldehyde- N (4)-methylthiosemicarbazone) and [Cu(acetylethTSC)Cl]Cl•0.25C 2 H 5 OH 2 (where acetylethTSC = (E)-N -ethyl-2-[1-(thiazol-2-yl)ethylidene]hydrazinecarbothioamide) was investigated by analyzing DNA cleavage activity. The cytotoxic effect was analyzed using CCK-8 viability assay. The activities of caspase 3/7, 9, and 1, reactive oxygen species (ROS) production, cell cycle arrest, and mitochondrial function were further analyzed to study the cell death mechanisms. Complex 2 induced a significant increase in nicked DNA. The IC 50 values of complex 1 were 17.59 μM and 61.26 μM in cancer and non-cancer cells, respectively. The IC 50 values of complex 2 were 5.63 and 12.19 μM for cancer and non-cancer cells, respectively. Complex 1 induced an increase in ROS levels, mitochondrial dysfunction, and activated caspases 3/7, 9, and 1, which indicated the induction of intrinsic apoptotic pathway and pyroptosis. Complex 2 induced cell cycle arrest in the S phase, ROS generation, and caspase 3/7 activation. Thus, complex 1 induced cell death in the breast cancer cell line via activation of oxidative stress which induced apoptosis and pyroptosis while complex 2 induced cell cycle arrest through the induction of DNA cleavage.