Osteosarcoma (OS) is a highly aggressive bone cancer that primarily affects young adults. The tumor microenvironment and molecular mediators, including Janus kinases (JAKs) and matrix metalloproteinases (MMPs), significantly influence OS metastasis
activation of the JAK/STAT pathway enhances MMP expression and activity, promoting OS metastasis. 7-Geranyloxycoumarin, a natural agent found in various edible fruits and vegetables, possesses valuable pharmaceutical activities. This study aimed to investigate the effects of 7-geranyloxycoumarin on the metastasis of OS cells for the first time. To achieve this, a protein-protein interaction (PPI) network was constructed from the potential molecular and pathogenic targets associated with 7-geranyloxycoumarin and OS to identify overlapping targets. Subsequently, GO and KEGG pathway enrichment analyses were conducted. Molecular docking and dynamic simulations were also performed to elucidate the binding affinity of 7-geranyloxycoumarin with JAK1 and JAK2. For in vitro studies, 7-geranyloxycoumarin was first extracted from Ferula szowitsiana using thin-layer chromatography. The cells were then treated and evaluated for viability, apoptosis, migration, invasion, adhesion, and MMPs activity. The study identified 50 shared targets and revealed MMP-2, MMP-9, JAK1, and JAK2 as hub genes, confirmed through enrichment analyses. Molecular docking revealed strong interactions between 7-geranyloxycoumarin and JAK1 and JAK2 proteins, and molecular dynamics simulations indicated both conformational flexibility and binding stability of the ligand-protein complex. Moreover, experimental studies demonstrated that 7-geranyloxycoumarin did not induce apoptosis but significantly altered the migration, invasion, and adhesion of OS cells by inhibiting the activity of MMPs. In conclusion, 7-geranyloxycoumarin is proposed as a promising therapeutic agent for targeting metastasis in OS cells.