Evaluation of the Cytotoxic and Antimigratory Activity Induced by [Pt(1-hexyl-1H-imidazole)(η1-C2H4OEt)(phen)]Cl in Pancreatic Ductal Adenocarcinoma Cells.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by poor prognosis and marked resistance to chemotherapy. In this study, we investigated the cytotoxic and antimigratory effects of a cationic monofunctional organometallic platinum (II) complex containing 1,10-phenanthroline (phen), [Pt(1-hexyl-1H-imidazole)(η1-C2H4OEt)(phen)]Cl, in comparison with cisplatin in the cisplatin-resistant YAPC pancreatic cancer cell line. The complex exhibited a rapid and potent cytotoxic effect, significantly reducing cell viability within a few hours of treatment and showing greater short-term activity than cisplatin. This enhanced efficacy was associated with a markedly higher and faster intracellular accumulation, suggesting improved cellular uptake. Mechanistically, the compound induced apoptosis more effectively than cisplatin, as demonstrated by flow cytometry, and caused an early and pronounced loss of mitochondrial membrane potential (ΔΨM), indicating mitochondrial involvement in cell death. In addition, the complex significantly impaired cell motility in both transwell and 3D spheroid-based assays, confirming a strong antimigratory and anti-dissemination potential. Overall, these findings indicate that [Pt(1-hexyl-1H-imidazole)(η1-C2H4OEt)(phen)]Cl represents a promising candidate for targeting cisplatin-resistant PDAC cells, owing to its rapid cellular uptake, mitochondrial-mediated apoptotic signaling, and combined cytotoxic and antimigratory properties.