Selective anticancer activity of a multinuclear Cu(II) complex through apoptosis induction in ovarian cancer cells

Copper Cu(II)-based coordination compounds have attracted considerable attention as potential alternatives to platinum-based anticancer agents because of their diverse mechanisms of action and improved selectivity. In this study, a multinuclear Cu(II) complex, [Cu(DMPN)₂(H₂O)][Cu₂(μ-DPA)₄Cu(DMPN)₂].H₂O (Cu-DPA-DMPN), was investigated for its anticancer activity against human ovarian carcinoma (OVCAR-3) cells. The complex was characterized by FTIR spectroscopy and ESI-MS, confirming successful coordination of DPA and DMPN ligands to the Cu(II) centers. Cytotoxicity assays demonstrated dose- and time-dependent antiproliferative activity, with IC₅₀ values of 73.06 μM and 35.75 μM after 48 and 72 h, respectively, while exhibiting lower toxicity toward non-malignant CHO cells (IC₅₀ = 334.19 μM at 48 h). Flow cytometry revealed a significantly higher percentage of early apoptotic cells following Cu-DPA-DMPN treatment than with cisplatin. Gene expression analysis showed marked upregulation of Caspase-3 (160.9-fold) and suppression of AKT1 (0.12-fold), indicating activation of apoptotic signaling and inhibition of cell survival pathways. JC-1 analysis further demonstrated mitochondrial membrane depolarization, supporting the functional involvement of mitochondria during apoptosis. In addition, the complex did not significantly increase TLR6 expression in CHO cells, suggesting minimal inflammatory effects on normal cells. These findings demonstrate that the Cu-DPA-DMPN complex exhibits selective anticancer activity by promoting apoptosis while displaying reduced toxicity toward normal cells, highlighting its potential as a promising candidate for ovarian cancer therapy.