Murraya koenigii extract potential as a herbal alternative therapeutic agent for inhibiting lung cancer cell migration via suppression of MMP-2 and MMP-9 activity

Lung cancer, particularly non-small cell lung cancer (NSCLC), is documented as the leading cause of cancer-related deaths worldwide. This is emphasized by the elevated metastatic ability observed in advanced NSCLC cases, a process primarily mediated by increased activity of matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9). Interestingly, despite showing no cytotoxicity against the NSCLC cell line, Murraya koenigii demonstrated anti-migratory activity, as indicated by the stagnation of the wound area observed in treated NSCLC cells in vitro. This effect is mediated through the inhibition of MMP-2 and MMP-9 enzymatic activity. Notably, M. koenigii leaf extract exerted this activity at concentrations as low as 14 µg/mL, and increasing the extract concentration did not significantly affect its inhibitory potential. Compound testing and molecular docking further indicated that MMP-9 inhibition was achieved through direct binding between the extract’s high flavonoid content, particularly rutin, and alkaloids with the MMP-9 active site. Despite binding at different residues compared with the known inhibitor, the bioactive compounds, especially mahanine, also exhibited high binding affinity to both MMP-2 and E-cadherin. Overall, the results of this study indicate the potential of M. koenigii leaf extract as an alternative anti-migratory treatment to improve the prognosis of patients with advanced metastatic NSCLC.