A mixed‐ligand copper(II) complex that inhibits growth and induces apoptosis by DNA targeting in human epithelial cervical cancer cells

• Published in: Applied organometallic chemistry Vol. 31; no. 7
• Main Authors: Ma, Zhong‐Ying, Qiao, Zheng, Wang, Dong‐Bo, Hou, Xuan, Qiao, Xin, Xie, Cheng‐Zhi, Qiang, Zhao‐Yan, Xu, Jing‐Yuan
• Format: Journal Article
• Language: English
• Published: Chichester Wiley Subscription Services, Inc 01.07.2017
• Subjects: anticancer; Apoptosis; Assaying; Bioassays; Cell cycle; Cervical cancer; Chemistry; Cleavage; Coordination compounds; Copper compounds; copper(II) complex; crystal structure; Damage; Damage detection; Deoxyribonucleic acid; Distortion; DNA; Fragmentation; Hydrogen peroxide; Ligands; mixed ligand; Oxidation; Serum albumin; Strong interactions (field theory); Toxicity
• ISSN: 0268-2605; 1099-0739
• DOI: 10.1002/aoc.3651

A new mixed‐ligand copper(II) complex, [Cu(L)(phen)]⋅MeOH (L = 4‐chloro‐2‐[(2‐hydroxyphenyl)iminomethyl]phenol), was synthesized. It belongs to the orthorhombic crystal system and Cu(II) is five‐coordinated in a seriously distorted square pyramidal geometry. DNA binding experiments confirmed an intercalative mode of interaction of the complex with calf thymus DNA. In a DNA cleavage experiment with the complex, as hydrogen peroxide was involved, oxidative DNA cleavage occurred and double‐stranded breaks even appeared at certain concentration. The strong interaction with bovine serum albumin suggested that the complex might be transported by protein. The complex exhibited more significant cytotoxicity in HeLa cells (IC50 = 0.46 ± 0.01 μM) for 48 h, compared with cisplatin (10.61 ± 0.86 μM). This work indicated that the complex could induce apoptosis in a dose‐dependent manner and was associated with cell cycle arrest to some extent. Being consistent with the results of DNA cleavage experiment, comet assay indicated that the complex induced severe DNA fragmentation. The results showed the production of reactive oxygen species increased with increasing concentration of the complex. The complex was suggested to be capable of promoting HeLa cell apoptosis through an oxidative DNA damage pathway. The novel mixed‐ligand copper(II) complex [Cu(L)(phen)]⋅MeOH (L = 4‐chloro‐2‐[(2‐hydroxyphenyl)iminomethyl]phenol) targeted DNA and displayed strong DNA cleavage activity, as well as cytotoxicity towards HeLa cells via an oxidative DNA damage pathway.