68Ga-PSMA-11 uptake in tracheal mucus plug - a potential pitfall.

UNLABELLED: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer occurring worldwide. The non-specificity and toxic side effects of conventional anti-cancer drugs have encouraged researchers to seek safer alternatives from natural sources. Atranorin, a depside group of secondary metabolites found in various lichens, possesses several pharmacological properties. Therefore, we aimed to investigate the anti-lung cancer activity of atranorin. For that, the anti-proliferative effect of atranorin was assessed and compared to that of doxorubicin against A549 lung cancer cells and BEAS-2B normal cells. Subsequently, a range of microscopic and flow cytometric evaluations were conducted to determine the apoptotic efficacy of atranorin. Furthermore, network pharmacology, combined with molecular docking, facilitated the identification of key targets. Finally, a molecular dynamics simulation was performed to verify the stability of the atranorin-target complex. Results reveal that IC50 of atranorin is 15.05 ± 1.18 µM against A549 cells and has a significantly higher selectivity index than the standard drug doxorubicin. Atranorin induced robust apoptosis in the A549 cells through upregulation of phospho-p53 expression. Apoptosis was associated with the generation of intercellular ROS. A significant disruption of mitochondrial membrane potential and upregulation of Caspase-9 expression indicated that apoptosis occurred via the intrinsic pathway. Network pharmacology identified a potential target, Matrix metalloproteinase-9 (MMP-9), and in silico docking analysis revealed that atranorin has a higher binding affinity for MMP-9 than doxorubicin. Additionally, molecular dynamics simulation demonstrated the stability of the atranorin-MMP-9 complex through several parameters. Therefore, in silico and in vitro experiments confirmed the significant anticancer activity of atranorin against A549 cells.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s40203-026-00729-x.