The cytotoxicity of palladium (II) complexes containing 1,2‐ or 1,4‐diazine bridging ligands on squamous cell carcinoma cells in vitro: Insights in the mechanisms of action

Binuclear [{Pd (dien)}2(μ‐pz)](ClO4)4 (Pd1) and [{Pd (dien)}2(μ‐pydz)](ClO4)4 (Pd2) complexes, where pz is 1,4‐diazine and pydz is 1,2‐diazine bridging ligands and dien (diethylenetriamine) is a tridentately coordinated triamine ligand, were synthesized and characterized using elemental analysis, NMR (1H and 13C) spectroscopy, and UV–Vis spectrophotometry. Electronic absorption spectrophotometry and fluorescence spectroscopy were used to study the interactions of the prepared Pd1 and Pd2 complexes with deoxyribonucleic acid (CT‐DNA) and bovine serum albumin (BSA). According to the UV–Vis spectrophotometric data, the complexes interact with CT‐DNA and bind to the BSA as a possible carrier to the target site. The antitumor properties of the tested palladium compounds were evaluated on three types of human cancer cells, namely, squamous cell carcinoma cells SCC‐4, cervical carcinoma cells HeLa and colorectal carcinoma cells HCT116, and one type of malignantly unchanged cells, MRC‐5 fibroblasts. The highest cytotoxicity was shown by the Pd1 compound against SCC‐4 cell, with an IC50 value of 5.4 ± 1.2 μM. The results showed that the cytotoxic potential against SCC‐4 cells of our new palladium complexes Pd1 and Pd2 was comparable with the cytotoxic potential of cisplatin and oxaliplatin. However, Pd1 and Pd2 displayed significantly lower cytotoxicity in comparison with cisplatin and oxaliplatin against non‐malignant cells, fibroblasts MRC5, so these results may suggest that local and systemic complications of antitumor therapy could be reduced and/or avoided. Both compounds selectively decreased the viability of SCC‐4 cells by induction of apoptosis. Also, Pd1 and Pd2 induced S‐phase cell cycle arrest in human SCC‐4 cells, so that could be another mechanism to halt the uncontrolled growth and division of cancer cells. Moreover, the precise molecular mechanism of Pd1 and Pd2 complexes‐induced apoptosis was the activation of the intrinsic signaling pathway of apoptosis, which also included activation of caspase‐3. Therefore, our new palladium (II) complexes might have a promising role as the potential future cytostatic agents.