ABSTRACT
Four palladium(II) and platinum(II) saccharinate (sac) complexes with 2-(hydroxymethyl)pyridine (2-hmpy) and 2-(2-hydroxyethyl)pyridine (2-hepy), namely trans-[Pd(2-hmpy)2(sac)2]·H2O (1), trans-[Pt(2-hmpy)2(sac)2]·3H2O (2), trans-[Pd(2-hepy)2(sac)2] (3) and trans-[Pt(2-hepy)2(sac)2] (4), have been synthesized and characterized by elemental analysis, UV-vis, IR and NMR. Single crystal X-ray analysis reveals that the metal(II) ions in each complex are coordinated by two sac and two 2-hmpy or 2-hepy ligands with a trans arrangement. Anticancer effects of 1-4 were tested against four different cancer cell lines (A549 and PC3 for lung cancer, C6 for glioblastoma, and Hep3B for liver cancer). Cytotoxicity was first screened by the MTT assay and the results were further confirmed by the ATP assay. The mode of cell death was determined by both histological and biochemical methods. Among the metal complexes, complex 2 resulted in relatively stronger anti-growth effect in a dose-dependent manner (3.13-200µM), compared to the others, by inducing apoptosis.
Subject(s)
Antineoplastic Agents/chemical synthesis , Coordination Complexes/chemical synthesis , Palladium/chemistry , Pyridines/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/toxicity , Apoptosis/drug effects , Caspase 3/metabolism , Cell Line, Tumor , Coordination Complexes/chemistry , Coordination Complexes/toxicity , Crystallography, X-Ray , Humans , Isomerism , Keratin-18/metabolism , Molecular Conformation , Saccharin/chemistry , Structure-Activity RelationshipABSTRACT
Anti-cancer effects of a newly-synthesized palladium(II) complex, [Pd(sac)(terpy)](sac)·4H(2)O (sac = saccharinate, and terpy = 2,2':6',2''-terpyridine), were tested against human breast cancer cell lines, MCF-7 and MDA-MB-231. The Pd complex had a strong anti-growth effect in a dose- and time-dependent manner in vitro. This effect was also confirmed by the experiment performed on Balb/c mice in vivo. The IC(50) values were 0.09 µM for MDA-MB-231 and 3.05 µM for MCF-7. It was also very effective in disrupting the formation of MDA-MB-231 tubules on matrigel, indicative of a putative anti-invasive activity. It induced apoptosis via the cell death genes of DR4 and DR5. In conclusion, this newly-synthesized Pd (II) complex represents a potentially active novel drug for the breast cancer treatment.
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Palladium/chemistry , Palladium/therapeutic use , Animals , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , Coordination Complexes/chemistry , Coordination Complexes/pharmacology , Coordination Complexes/therapeutic use , Female , Humans , Mice , Mice, Inbred BALB C , Palladium/pharmacologyABSTRACT
PURPOSE: Treatment for lung cancer is still far from satisfying rates. Therefore, there is a need for novel anticancer agents. For this purpose, novel platinum and palladium complexes {[Pd(sac)(terpy)](sac)·4H(2)O (Complex 1), [Pt(sac)(terpy)](sac)·5H(2)O (Complex 2), [PdCl(terpy)](sac)·2H(2)O (Complex 3), [PtCl(terpy)](sac)·2H(2)O (Complex 4)} have been tested against three different non-small cell lung cancer cell lines (A549, H1299, PC-3). METHODS: Growth-inhibiting effects have been tested by the MTT and ATP viability assays. Apoptosis has been detected by the caspase-cleaved cytokeratin 18 (M30-antigen) assay. Necrosis has been detected by staining the cells with fluorescent dyes. Mitotic index has been calculated by counting the mitotic figures after staining with hematoxylin. RESULTS: The complex 3 exhibited significant anti-growth effects, and its anti-growth effect was more powerful than that of cisplatin that is a standard chemotherapeutic agent for this type of cancer. The complexes did not induce apoptosis, while necrosis clearly took place. CONCLUSIONS: Novel Pd(II) complex ([PdCl(terpy)](sac)·2H(2)O) seems to represent a potentially active drug against non-small cell lung cancer cell lines, and further studies in vivo are warranted.
Subject(s)
Apoptosis/drug effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Organometallic Compounds/pharmacology , Organoplatinum Compounds/pharmacology , Palladium/pharmacology , Adenosine Triphosphate/analysis , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Cisplatin/pharmacology , Humans , Lung Neoplasms/pathology , Mitosis/drug effects , NecrosisABSTRACT
New palladium(II) and platinum(II) complexes of saccharinate (sac) with 2-(2-pyridyl)benzimidazole (pybim) have been synthesized and characterized by elemental analysis and spectroscopic techniques. From the experimental studies, these complexes were formulated as [Pd(pybim)(sac)2] (1), and [Pt(pybim)(sac)2]·4H2O (2). The ground-state geometries of both complexes were optimized using density functional theory (DFT) methods at the B3LYP level. A bidentate pybim ligand together with two N-coordinated sac ligands form the square-planar MN4 coordination geometry around the palladium(II) and platinum(II) ions. The calculated IR and UV-vis spectral data have been correlated to the experimental results. Thermal analysis data support the molecular structures of both complexes.
