Cytotoxic activity of biosynthesized nickel oxide nanoparticles against A549 lung cancer cell line

Lung cancer continues to be the leading cause of cancer-related fatalities worldwide. The advent of nanotechnology offers a promising solution for targeting cancer cells. The biosynthesis approach was chosen because phytocompounds present in plant extracts function as capping and reducing agents. Herein, we produced Piper nigrum seed extract-mediated nickel oxide nanoparticles (PNNO NPs), and the cytotoxicity they induced in the A549 lung cancer cell line was investigated. XRD studies confirmed the formation of PNNO NPs crystallized in a cubic crystal system with the Fm3̄m (225) space group. FESEM analysis showed that these NPs were less agglomerated, with a mean particle size of 26 nm. Evaluation of anticancer activity using the MTT assay revealed that PNNO NPs exert high toxicity towards A549 lung cancer cells, with a half-maximal inhibitory concentration (IC₅₀) of 19 µg mL^-1. H₂-DCFDA and JC-1 biochemical staining confirmed a substantial increase in the reactive oxygen species generation and mitochondrial damage in PNNO NP-treated A549 cancer cells, respectively. AO/EtBr staining and flow cytometry analysis indicated that A549 cancer cells subjected to PNNO NPs underwent apoptosis, and this was strongly supported by the downregulation of the mRNA expression of the antiapoptotic gene BCL2. Collectively, these compelling results highlight the substantial therapeutic potential of PNNO NPs as an effective agent for combating lung cancer.