Olga Klaudia Szewczyk-Roszczenko, Piotr Roszczenko, Nurbey Gulia, Jarosław Fornalski, Adrianna Gumienna, Krzysztof Bielawski, Sławomir Szafert, Robert Czarnomysy
Abstract The development of novel metal-based anticancer agents with higher selectivity and lower toxicity is a major goal in oncology. In this study, four newly synthesized palladium(II) complexes (1a, 1b, 1c, 2a) were tested for cytotoxicity against breast cancer cell lines MCF-7 and MDA-MB-231, with cisplatin as reference. Complexes 1a, 1b, and 2a showed strong activity, particularly in MCF-7. Flow cytometry revealed that complex 2a induced S-phase arrest in MCF-7 and G2/M arrest in MDA-MB-231. ROS detection assays confirmed a marked increase in oxidative stress after 2a treatment, accompanied by mitochondrial membrane potential loss. Furthermore, caspase-9 and caspase-8 activation, along with downstream caspases 3 and 7, indicated engagement of both intrinsic and extrinsic apoptotic pathways. Among the tested compounds, palladium complex 2a exhibited the most potent and multifaceted anticancer activity. These results highlight 2a as a promising candidate scaffold for further development of novel chemotherapeutics targeting breast cancer.