From Patient Selection to Surveillance: Artificial Intelligence Applications in Radioiodine Therapy - A Systematic Review.

UNLABELLED: Dietary phytochemicals exhibit anticancer activity, and increasing evidence suggests that the combinations of co-occurring compounds may provide greater therapeutic efficacy than individual compounds. Eruca sativa Mill. (rocket salad) contains both erucin and kaempferol; however, their synergistic anticancer activity against non-small cell lung cancer (NSCLC) has not been systematically investigated. Network pharmacology, molecular docking, and molecular dynamics (MD) simulations were performed to identify molecular targets of erucin and kaempferol. Their synergistic anticancer activity was subsequently evaluated in A549 (NSCLC) cells using the MTT assay and the combination index (CI) analysis, followed by a cell migration assay, fluorescence microscopy, flow cytometry, biochemical assays, caspase-3/7 assay, and RT-qPCR to investigate the underlying mechanisms. The combination of erucin (20 µM) and kaempferol (40 µM) exhibited the strongest synergistic interaction (Combination Index, CI = 0.428), significantly inhibiting A549 cell growth and migration while exhibiting preferential cytotoxicity toward A549 cells with minimal effects on WI-38 lung fibroblasts. Combined treatment increased overall oxidative stress, induced mitochondrial membrane depolarisation, enhanced caspase-3/7 activity and apoptosis, and modulated Bax/Bcl-2 gene expression, indicating activation of the intrinsic mitochondrial apoptotic pathway. Computational analyses identified EGFR as a potential molecular target that may contribute to the observed anticancer effects. The erucin-kaempferol combination demonstrated synergistic anticancer activity against A549 NSCLC cells, highlighting the bioactive potential of naturally co-occurring E. sativa-derived phytochemicals. However, these findings are limited to computational and in vitro studies, and in vivo studies are required to validate their therapeutic efficacy and elucidate the underlying molecular mechanisms.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10616-026-01049-w.