Assessment of cytotoxicity and antitumor activity of newly developed compounds in A549 lung cancer cells

Abstract

Lung cancer is among the most common cancers in the world, and current treatments are inadequate due to the development of resistance and serious side effects. This situation brings new therapeutic strategies for cancer treatment. Among these, silver-based N-heterocyclic carbenes (Ag-NHCs) have emerged as promising candidates due to their unique chemical properties, such as strong metal-ligand bonding and modulation of biological reactivity. This study investigates the cytotoxic and antitumoral effects of newly synthesized Ag-NHC complexes on lung cancer (A549) cells. Ag-NHC complexes (X, Y, and Z) were synthesized using benzimidazolium salts and characterized by NMR spectroscopy. Cytotoxicity was evaluated on A549 and normal fibroblast (L929) cells using MTS assays. Apoptotic cell death and mitochondrial membrane potential were evaluated in A549 cells. Gene expression analysis for apoptosis-related markers was performed using RT-PCR. Ag-NHC complexes showed dose- and time-dependent antiproliferative effects in the A549 cell line. Annexin V/PI analysis revealed significant apoptotic induction by complexes X, Y and Z; the highest apoptotic rates were observed in A549 cells treated with Y and Z. Complexes Y and Z significantly decreased mitochondrial membrane potential, indicating increased apoptosis via intrinsic pathways. RT-PCR revealed increased pro-apoptotic gene expression (Bax, BAD, caspase-3, -8, -9) and decreased anti-apoptotic Bcl-2 expression in treated A549 cells. Complexes Y and Z also upregulated extrinsic apoptotic markers (DR4 and DR5). The newly synthesized Ag-NHC complexes (X, Y, Z) exhibited significant antiproliferative and pro-apoptotic effects in A549 lung cancer cells, indicating their potential as new therapeutic agents with reduced toxicity compared to conventional chemotherapy.

Keywords

• Ag-NHC
• Apoptosis
• Lung cancer

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