RNA sequencing of A549 lung cancer cells treated with a copper(I) bisphosphine complex (Complex 1)

Copper-based complexes are emerging as promising anticancer agents, yet their mechanisms of action remain incompletely understood. In this study, we evaluated a series of novel bisphosphine copper(I) thiocarbamide complexes and identified Complex 1, a bis(triphenylphosphine) copper(I) iodide complex bearing a thiocarbamide ligand, as exhibiting selective cytotoxicity toward lung cancer cells with reduced toxicity in normal fibroblasts. To elucidate its mechanism of action, whole transcriptome profiling was conducted on A549 cells following treatment with Complex 1. Cells were treated with 5 µM Complex 1 or vehicle control (DMSO) for 72 hours prior to RNA extraction. Differential gene expression analysis revealed modulation of pathways associated with p53 signalling, NF-κB signalling, and cell cycle regulation. These findings were supported by functional assays showing G2/M cell cycle arrest, indicating disruption of cell cycle progression as a primary mode of action, with apoptosis contributing to a lesser extent. Overall, this study demonstrates that novel bisphosphine copper(I) thiocarbamide complexes can exert selective anticancer activity and provides mechanistic insight into their effects on cancer-associated signalling networks, supporting their further development as therapeutic candidates.