Abstract
Cisplatin is one of the most widely used chemotherapeutic agents in the treatment of different tumors but has high toxicity and side effects. Therefore, the synthesis of new chemotherapeutic agents is necessary, so that they are effective in the treatment of cancer while avoiding such toxicity. In this study, we have synthesized and characterized a palladium(II) complex, [PdCl2(µ-PyTT)2]Cl2·4H2O (PdPyTT), with 2-(2-pyridyl)imine-N-(2-thiazolin-2-yl)thiazolidine (PyTT) as a ligand; besides, its cytotoxicity and pro-apoptotic capacity was tested in human promyelocytic leukemia HL-60 cell line. Similar to cisplatin, PdPyTT produced a time- and dose-dependent decrease in cell viability. Additionally, the palladium complex increased both the proportion of cells with apoptotic morphology and the activation of caspase-3 and -9. PdPyTT, like cisplatin, also increased intracellular ROS production and DNA oxidative damage. Therefore, our findings demonstrated the promising application of palladium(II) complexes as novel anti-leukemic agents.
Highlights
Cisplatin and its derivatives are common chemotherapeutic agents used to treat different cancers since they can activate cell death mechanisms in cancer c ells[1,2,3,4]
The effect of cisplatin and PdCl2(μ-PyTT)2] Cl2·4H2O (PdPyTT) on the localised production of mitochondrial superoxide anion was similar (22.3 ± 2.2 and 22.5 ± 6.4% of positive cells, respectively; Fig. 5C), while PdPyTT was more effective in inducing intracellular overproduction of reactive oxygen species (ROS) (55.7 ± 16.7% of positive cells; Fig. 5C) compared with the effect of cisplatin (10.3 ± 4.4% of positive cells; Fig. 5C). These findings suggest that the complex PdPyTT displayed potent antitumor actions that relied on its ability to trigger caspase-9-dependent mitochondrial apoptosis, on one hand, and to cause excessive formation of cytosolic and mitochondrial ROS, on the other hand
Palladium(II)-based complexes represent an appealing alternative to classical antitumor drugs as they possess promising chemotherapeutic properties including covalent interaction with nitrogen bases of DNA, activation of either the extrinsic or the intrinsic apoptosis pathway, blockade of cell cycle progression, and induction of ROS overproduction that leads to oxidation of b iomolecules[54]
Summary
Cisplatin and its derivatives are common chemotherapeutic agents used to treat different cancers since they can activate cell death mechanisms in cancer c ells[1,2,3,4]. Thiazolines are thiazole-derived heterocycles bearing a single double bond as well as nitrogen and sulphur atoms. In this sense, it has been shown that 2-thiazoline-based oligomers induce cytotoxicity in HPAC, PC-3, and HCT-116 human cell lines (pancreatic, prostate and colon cancer, respectively)[12]. Platinum(II) and palladium(II) complexes containing 2-mercaptothiazoline have been shown to produce remarkable cytotoxic actions against hepatoma cells[17] In this line, we have recently demonstrated that platinum(II) and palladium(II) complexes containing a thiazoline derivative ligand reduced proliferation capacity and induced apoptosis in both colon HT-29 and lymphoma U-937 cell lines[18]. We aimed to study the potential cytotoxic and pro-apoptotic capacity of the complex PdPyTT in human promyelocytic leukemia HL-60 cells
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