Apoptosis, Oxidative Stress, and Cell Cycle Disruption: Antitumor Effects of a Novel Palladium(II) Complexes

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 (<b>1a</b>, <b>1b</b>, <b>1c</b>, <b>2a</b>) were tested for cytotoxicity against breast cancer cell lines MCF-7 and MDA-MB-231, with cisplatin as reference. Complexes <b>1a</b>, <b>1b</b>, and <b>2a</b> showed strong activity, particularly in MCF-7. Flow cytometry revealed that complex <b>2a</b> 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 <b>2a</b> 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 <b>2a</b> exhibited the most potent and multifaceted anticancer activity. These results highlight <b>2a</b> as a promising candidate scaffold for further development of novel chemotherapeutics targeting breast cancer.