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 (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.