Mechanistic investigation of the cytotoxicity of new Ce(IV) and Zn(II) complexes containing pyridinedicarboxylic acid derivatives against the SW480 cell line

• Published in: Journal of molecular structure 2025-01, Vol.1319, p.139377, Article 139377
• Main Authors: Aliabadi, Alireza, Abdolmaleki, Sara, Khaksar, Samad
• Format: Article
• Language: English
• Subjects: Apoptosis; Cerium(IV) complex; Cytotoxicity; Reactive oxygen species (ROS); Zinc(II) complex
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2024.139377

•Cerium(IV) and zinc(II) complexes containing pyridinedicarboxylic acid derivatives are synthesized and characterized.•The direct dependence between the cytotoxicity of synthetic complexes and their electrochemical activity is recognized.•Apoptotic and autophagic cell death is confirmed in SW480 cells treated with complexes.•Change in tumor size in vitro in SW480 3D spheroid model treated with the complexes is demonstrated. Two cerium(IV) (C1) and zinc(II) (C2) complexes formulated as (aeea)2[Ce(pydc)3].5H2O (where pydc is pyridine-2,6-dicarboxylate and aeea is aminoethylethanolamine) and [Zn(hpydc)(dmp)].2H2O (where hpydc is 4-hydroxy-pyridine-2,6-dicarboxylate and dmp is 2,9-dimethyl-1,10-phenanthroline) were obtained by a one-pot reaction of organic ligands and the metal salts Ce(NO3)2.6H2O and Zn(NO3)2.6H2O. The complexes were characterized by spectroscopic methods and single-crystal X-ray diffraction. The MTT assay was performed for the compounds against four cell lines, including human hepatocellular carcinoma (BEL-7404), primary human colon cancer (SW480), metastatic human colon cancer (SW620) and normal human colon tissue (CCD841CoN), which showed the highest sensitivity to C1 (IC50= 1.89 μM, MAE= 72.46%) (where MAE represents the maximal antiproliferative effect). C1 demonstrated its ability as a redox-active compound to generate high levels of reactive oxygen species (ROS) in this cell line. Mechanistic investigation of the efficacy of the compounds on SW480 cells showed that C1 can induce bimodal cell death by both (intrinsic and extrinsic) apoptosis and autophagy, whereas only the intrinsic apoptosis pathway was detected when the aforementioned cells were treated with C2. SW480 cells treated with C1 showed remarkable morphological changes as well as a reduction in tumor size in the SW480 3D spheroid model. [Display omitted]