Investigating Anticancer Properties of Artemisia annua in Human Pancreatic Cancer Cells: Insights from Network Pharmacology, Molecular Docking, Dynamics Simulations, and Experimental Testing

This study examines the bioactive compounds of Artemisia annua (A. annua) and their therapeutic potential in treating Prostate Cancer (PC) through network pharmacology, bioinformatics, and in vitro validation. It screened ۱۲۶ bioactive principles from the TCMSP database and then reduced them to ۲۲ based on drug-likeness, oral bioavailability, and permeability. The subsequent screening yielded ۳۹۶ biological targets, with possible duplicates eliminated, and further reduced to ۷۲ putative targets. The comparative analysis with ۱۴,۱۴۶ PC-related genes resulted in the identification of ۶۲ common targets. Network analysis highlighted three major compounds, Kaempferol, Sitosterol, and Quercetin, which interact with these targets. Molecular docking indicated strong binding affinities of Kaempferol to key hub genes EGFR, MMP۹, and GSK۳B (Vina scores: -۸.۴, -۹.۰, -۷.۷) that were further supported by stable interactions in molecular dynamics simulations. In vitro studies indicated that the ethanol-DCM extract of A. annua exhibited statistically significant cytotoxic effects on PANC-۱ cells. Cell viability assays showed dose- and time-dependent inhibition after ۴۸ hours of treatment. Migration and invasion assays showed a significant reduction in cell movement across transwell membranes at ۶۰ µg/mL (p < ۰.۰۱) and ۱۲۰ µg/mL (p < ۰.۰۰۱). Invasiveness was also significantly suppressed at ۶۰ µg/mL (p < ۰.۰۱) and ۱۲۰ µg/mL (p < ۰.۰۰۱), indicating anti-metastatic potential. Flow cytometric cell cycle analysis showed significant G۲/M-phase arrest and ۴۵.۶% of cells arrested in G۲/M-phase at ۱۲۰ µg/mL compared to ۱۸.۴% in the untreated controls were found (p < ۰.۰۰۱). Annexin V-FITC/PI staining evidenced apoptosis induction, with ۲۸.۳% apoptotic cells at ۱۲۰ µg/mL levels compared to ۶.۱% in controls (p < ۰.۰۰۱). These findings demonstrate the potential of A. annua to modulate critical molecular pathways in PC, offering promising insights for developing novel therapeutic strategies.

کلیدواژه ها:

Artemisia annua ، Molecular Docking ، molecular dynamics ، Network Pharmacology ، Pancreatic Cancer ، Cell migration ، Cell cycle