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Antiproliferative Effects of Novel Copper (II) Complexes on Lung Cancer Cell Line

Abdullah, M. F.; cinkilic, N.; vatan, o.; inci, d.; Aydin, R.

2022-08-15 cancer biology
10.1101/2022.08.12.503805 bioRxiv
Show abstract

Copper is an essential metalloelement that plays key fundamental roles in both health and pathology, and is increasingly been implicated in molecular pathogenesis of many cancer types. It has shown promise as a replacement to cisplatin in coordination complexes presently in mainstream chemotherapeutic practices. In this study, two newly synthesized water-soluble ternary copper (II) mixed ligand complexes; complex 1 - (Cu(4-mphen)(tyr)(H2O)]NO3{middle dot}2H2O)(C.1) and complex 2 - (Cu(5-mphen)(tyr)(H2O)]NO3{middle dot}2H2O (C.2) where (4-m= 4-methyl; 5-m = 5-methyl; phen-1, 10 = phenanthroline; tyr = tyrosine)), were investigated on adenocarcinomic human alveolar basal epithelial cell, A549 and non-cancerous human bronchial epithelial cell, BEAS-2B for their antiproliferative effects using the XTT assay (cytotoxicity), Comet assay (genotoxicity) and DCFH-DA assay (intracellular ROS) tests. C.1 was significantly more cytotoxic in A549 than C.2. Data from the Comet and ROS assay tests support each other. C.2 caused more copper-induced DNA damage, possibly through significant induction of ROS-mediated oxidative damage in the cancer cell, but a minimal insignificant ROS rise in normal cells. These results can only be preliminary and further studies are required to better understand the cellular effects and functional interactions of these agents, for an efficient therapeutic design and application.

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